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Alraey Y, Assiry MM, Ahmad I, Rab SO, Alqahtani A, Bawazeer AAS, Hussien T, Syed Khaja AS, Saleem M. Hospital epidemiology and antimicrobial susceptibility of isolated methicillin-resistant Staphylococcus aureus: a 5-year retrospective study at a tertiary care centre in Aseer Region, Saudi Arabia. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04218-4. [PMID: 40299023 DOI: 10.1007/s00210-025-04218-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Accepted: 04/22/2025] [Indexed: 04/30/2025]
Abstract
Between 2019 and 2023, an analysis at the tertiary care centre revealed that 849 out of 1,951 Staphylococcus aureus isolates were methicillin-resistant (Staphylococcus aureus), commonly known as MRSA. According to statistical results, the rate of MRSA infection was markedly higher in patients who received inpatient department care (IPD) at 46.8% than in outpatient department (OPD) at 37.0% (p < 0.0001). Results showed males infected at a rate of 45.3% compared to females who had a rate of 39.4% (p = 0.0198) and age groups demonstrated no significant association (p > 0.05). The choice of specimen type affected MRSA detection rates as endotracheal tubes (32.5%, p = 0.004) together with 'Other' samples (e.g.: CSF, bone, bone marrow, bronchial lavage, abdominal aspirate, semen, ETT tip, femoral tip, jugular tip) (54.2%, p = 0.0068) presented higher proportions of infections. Individuals with benign prostatic hyperplasia showed an increased risk of MRSA infection (OR, 1.8; p < 0.0001) along with patients who had chronic lung disease (OR, 1.2; p = 0.048) or recent antibacterial substance use (OR, 2.5; p < 0.0001) while steroid use reduced the risk of MRSA infection (OR, 0.8; p = 0.002). MRSA showed complete resistance against β-lactam antibacterial substances, while all samples remained susceptible to Daptomycin, Linezolid, Nitrofurantoin, and Tigecycline. The sensitivity rate of vancomycin reached 95%, but MRSA displayed significantly reduced susceptibility to fluoroquinolones at 39.3% to 46.3% compared to MSSA, with rates at 81.5% to 85.5%. The percentage of macrolide-resistant bacteria was higher in MRSA, since they showed 28.3%-37.1% susceptibility rates, whereas MSSA had 61.3%-61.8% susceptibility rates. The anti-staphylococcal activity between MRSA and MSSA exceeded 94% for Rifampicin, Teicoplanin, and Fosfomycin. The antibacterial substances, Gentamicin and Tobramycin, showed high sensitivity against MSSA, since their sensitivity reached 92.3% and 91.3%, respectively. Both agents had good sensitivity against MRSA, with rates of 82.4% for gentamicin and 88.9% for tobramycin. Strict antimicrobial stewardship should be implemented as a priority to control the spread of MRSA. Last-line therapies such as vancomycin, daptomycin, and linezolid remain essential treatment options. Regular antimicrobial susceptibility testing is crucial for healthcare professionals to optimize therapy and prevent the development of drug resistance.
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Affiliation(s)
- Yasser Alraey
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Abdulaziz Alqahtani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | - Tarig Hussien
- Department of Obstetrics and Gynaecology, College of Medicine, University of Ha'il, Hail, Saudi Arabia
| | | | - Mohd Saleem
- Department of Pathology, College of Medicine, University of Ha'il, Hail, Saudi Arabia.
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Huang Z, Li Y, Yin W, Raby RBN, Liang H, Yu B. A magnetic-guided nano-antibacterial platform for alternating magnetic field controlled vancomycin release in staphylococcus aureus biofilm eradication. Drug Deliv Transl Res 2025; 15:1249-1264. [PMID: 39020245 DOI: 10.1007/s13346-024-01667-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/01/2024] [Indexed: 07/19/2024]
Abstract
Bacterial resilience within biofilms, rendering them up to 1000 times more resistant to antibiotic drugs, poses a formidable challenge. This study introduces a targeted biofilm eradication strategy, termed "target-penetration-killing-eradication", implemented through magnetic micro-robotic technology. Specifically, we present the development of a magnetic-guided nano-antibacterial platform designed for alternating magnetic field (AMF) controlled vancomycin release in the eradication of Staphylococcus aureus biofilms. To address the issue of premature vancomycin release in physiological conditions, we employed a temperature-sensitive linking agent, 4,4'-azobis(4-cyano valeric acid), facilitating the conjugation of vancomycin onto Fe3O4/CS nanocomposites, resulting in the novel construct Fe3O4@CS-ACVA-VH. The release mechanism adheres to first-order kinetics and Fickian diffusion, with each 10-min AMF treatment releasing approximately 8.4 ± 1.1% of vancomycin. The potency of vancomycin in the release solution was similar to that of the original drug (MIC: 7.4 ± 3.5 vs. 5.6 μg/mL). Fe3O4@CS-ACVA-VH exhibited sustained antibacterial efficacy, inhibiting bacterial growth for four consecutive days and preventing the formation of bacterial biofilms on its surface. Contact-inhibition bacterial activity of Fe3O4@CS-ACVA-VH against S. aureus was 0.046875 mg/mL. Conceptually validating our approach, we emphasize Fe3O4@CS-ACVA-VH's exceptional ability to penetrate S. aureus biofilms under static magnetic field attraction. Furthermore, the nano-platform offers the unique advantage of on-demand vancomycin release through alternating magnetic field stimulation, effectively clearing a larger biofilm area. This multifunctional nano-platform demonstrates magnetic-guided biofilm penetration followed by controlled vancomycin release, presenting a promising strategy for enhanced biofilm eradication.
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Affiliation(s)
- Zhi Huang
- Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410083, China
| | - Yuankai Li
- Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410083, China
| | - Wang Yin
- Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410083, China
| | - Randy Bachelard Nziengui Raby
- Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410083, China
| | - Haifeng Liang
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
- Department of Orthopedics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510150, China.
| | - Bo Yu
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
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Kim JY, Hwang H, Yim D, Choi Y, Kim TS, Whang J, Kwak N, Yim JJ. Relationship Between Clarithromycin Minimum Inhibitory Concentrations and Treatment Responses in Mycobacterium avium Complex Pulmonary Disease. Clin Infect Dis 2025; 80:637-643. [PMID: 39495674 DOI: 10.1093/cid/ciae546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/27/2024] [Accepted: 10/31/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear. METHODS We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into 4 groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the likelihood of microbiological cure. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis. RESULTS Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs ≤0.5, 1-2, 4-8, and ≥32 µg/mL, respectively (P = .181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (≤8 µg/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs ≥32 µg/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval [CI]: 0.06-1.07; P = .06). CONCLUSIONS Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range but were likely to be worse for patients with strains having MICs ≥32 µg/mL.
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Affiliation(s)
- Joong-Yub Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Microbiology, Harvard Medical School, Boston, United States
| | - Hyeontaek Hwang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - DaHae Yim
- Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yunhee Choi
- Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Taek Soo Kim
- Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jake Whang
- Research and Development Center, The Korean Institute of Tuberculosis, Cheongju, Republic of Korea
| | - Nakwon Kwak
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae-Joon Yim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Challa L, Villani MC, Hachem AA, Ma Y, Jo C, Patel K, Firmani S, Copley LA. Mitigating Risk of Acute Kidney Injury Among Children With Methicillin-resistant Staphylococcus aureus Osteomyelitis. J Pediatr Orthop 2025; 45:e172-e178. [PMID: 39350570 DOI: 10.1097/bpo.0000000000002808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
OBJECTIVE Children with acute hematogenous osteomyelitis (AHO) from methicillin-resistant Staphylococcus aureus (MRSA) are treated with vancomycin despite the risk of acute kidney injury (AKI). This study evaluates the rate of AKI and resource utilization for children with or without AKI when vancomycin is used in this setting. METHODS Children with MRSA AHO treated with vancomycin were retrospectively studied. AKI was assessed by clinical diagnosis and Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cohorts of children with or without AKI were compared for differences in treatment, resource utilization, and outcomes. Multivariate logistic regression analysis assessed factors associated with risk for AKI. Cost analysis was performed using the Pediatric Health Information System and Healthcare Cost and Utilization Project databases. RESULTS Among 85 children studied, 14 (16.5%) had chart-diagnosed AKI and 24 (28.2%) met KDIGO criteria. Children with AKI had more febrile days and higher thrombosis rates. They had longer vancomycin treatment (8 vs 5 d), higher troughs (27.8 vs 17.5 mg/L), and prolonged hospitalization (19.9 vs 11.1 d). Multivariate analysis found a maximum vancomycin trough level (odds ratio: 1.05, P = 0.003) with a cutoff of 21.7 mg/L predicted AKI.Only 2 of 20 (10%) children who had MRSA isolates with a minimum inhibitory concentration of 2 achieved therapeutic vancomycin levels. Pediatric Health Information System data of 3133 children with AHO treated with vancomycin identified 75 (2.4%) with AKI who had significantly longer lengths of stay (13 vs 7 d) and higher billed charges ($117K vs $51K) than children without AKI. CONCLUSIONS Chart documentation of AKI (16.5%) grossly underestimated KDIGO-defined occurrence (28.2%). This study showed that vancomycin-associated AKI required substantially greater resource utilization and higher health care costs. Lowering the targeted trough range, shortening the duration of vancomycin therapy, and considering alternative antibiotics when minimum inhibitory concentration ≥2 will reduce the risk and cost of AKI among children with MRSA AHO. LEVEL OF EVIDENCE Level III-retrospective comparative therapeutic study.
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Affiliation(s)
- Lasya Challa
- Division of Pediatric Hospital Medicine, University of Texas Southwestern
| | - Mary C Villani
- Division of Pediatric Infectious Diseases, University of Texas Southwestern
| | - Ahmad A Hachem
- Division of Pediatric Infectious Diseases, University of Florida, Jacksonville, FL
| | - Yuhan Ma
- Department of Research and Statistics, Scottish Rite Hospital for Children
| | - Chanhee Jo
- Department of Research and Statistics, Scottish Rite Hospital for Children
| | - Karisma Patel
- Department of Pharmacy, Children's Medical Center, Dallas, TX
| | - Sarah Firmani
- Department of Pharmacy, Children's Medical Center, Dallas, TX
| | - Lawson A Copley
- Department of Pharmacy, Children's Medical Center, Dallas, TX
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Authors/Task Force Members:, Jeppsson A, (Co-Chairperson) (Sweden), Rocca B, (Co-Chairperson) (Italy), Hansson EC, (Sweden), Gudbjartsson T, (Iceland), James S, (Sweden), Kaski JC, (United Kingdom), Landmesser U, (Germany), Landoni G, (Italy), Magro P, (Portugal), Pan E, (Finland), Ravn HB, (Denmark), Sandner S, (Austria), Sandoval E, (Spain), Uva MS, (Portugal), Milojevic M, (Serbia), EACTS Scientific Document Group
. 2024 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg 2024; 67:ezae355. [PMID: 39385505 DOI: 10.1093/ejcts/ezae355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/14/2024] [Accepted: 09/26/2024] [Indexed: 10/12/2024] Open
Affiliation(s)
| | - Anders Jeppsson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Bianca Rocca
- Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
- Department of Safety and Bioethics, Catholic University School of Medicine, Rome, Italy
| | | | - Emma C Hansson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Tomas Gudbjartsson
- Department of Cardiothoracic Surgery, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | | | - Stefan James
- Department of Medical Sciences, Uppsala University Uppsala Sweden
| | | | - Juan Carlos Kaski
- Molecular and Clinical Sciences Research Institute, St. George's University of London, UK
| | | | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine; Deutsches Herzzentrum Charité, Campus Benjamin Franklin, Berlin, Germany
- Charité-University Medicine Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH) at Charité Berlin, Universitätsmedizin Berlin, Germany
| | | | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | | | - Pedro Magro
- Department of Cardiac Surgery, Hospital Santa Cruz, Carnaxide, Portugal
| | | | - Emily Pan
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | | | - Hanne Berg Ravn
- Department of Anaesthesia, Odense University Hospital, Institute of Clinical Medicine, University of Southern, Denmark
| | | | - Sigrid Sandner
- Department of Cardiac Surgery, Medical University Vienna, Vienna, Austria
| | | | - Elena Sandoval
- Department of Cardiovascular Surgery, Hospital Clinic, Barcelona, Spain
| | | | - Miguel Sousa Uva
- Department of Cardiac Surgery, Hospital Santa Cruz, Carnaxide, Portugal
- Cardiovascular Research Centre, Department of Surgery and Physiology, Faculty of Medicine-University of Porto, Porto, Portugal
| | | | - Milan Milojevic
- Department of Cardiac Surgery and Cardiovascular Research, Dedinje Cardiovascular Institute, Belgrade, Serbia
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Collaborators
Matthias Siepe, Vesa Anttila, Lauren Barron, Dobromir Dobrev, Fabio Guarracino, Ziad Hijazi, Andreas Koster, Tomislav Kostic, Vladimir Lomivorotov, Vojislava Neskovic, Bjorn Redfors, Lars Peter Riber, Andrea Székely, Juan Tamargo, Theis Tönnessen, Alicja Zientara,
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Wheat W, Simiyu B, Andonie G, Bellfi L. Clinical Impact of Vancomycin MIC on Outcomes in Patients With Coagulase-negative Staphylococcal Bacteremia. Clin Ther 2024; 46:444-450. [PMID: 38493003 DOI: 10.1016/j.clinthera.2024.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 01/18/2024] [Accepted: 01/31/2024] [Indexed: 03/18/2024]
Abstract
PURPOSE Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. METHODS Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. FINDINGS There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). IMPLICATIONS There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.
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Affiliation(s)
- Wade Wheat
- University Medical Center New Orleans, New Orleans, Louisiana, USA
| | - Brenda Simiyu
- University Medical Center New Orleans, New Orleans, Louisiana, USA
| | - Gabriela Andonie
- University Medical Center New Orleans, New Orleans, Louisiana, USA; University of Louisiana Monroe College of Pharmacy, Monroe, Louisiana, USA.
| | - Lillian Bellfi
- University Medical Center New Orleans, New Orleans, Louisiana, USA
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Sarıcaoğlu EM, Yörük F. Antimicrobial Susceptibility of Various MRSA Clinical Isolates and the Impact of Glycopeptide MICs on Clinical and Microbiological Outcomes. INFECTIOUS DISEASES & CLINICAL MICROBIOLOGY 2024; 6:102-111. [PMID: 39005705 PMCID: PMC11243782 DOI: 10.36519/idcm.2024.330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 06/01/2024] [Indexed: 07/16/2024]
Abstract
Objective While vancomycin has remained the mainstay of the treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, there is growing evidence of the clinical impact of increased glycopeptide minimum inhibitory concentrations (MICs) in MRSA isolates. This study aimed to determine the susceptibility of various MRSA isolates to different antibiotics with antistaphylococcal activity and the impact of glycopeptide MICs on clinical and microbiological outcomes. Materials and Methods This retrospective cohort study, conducted between 2013 and 2017, evaluated the susceptibility of MRSA strains isolated from various clinical samples to antistaphylococcal antibiotics using the gradient strip method. The clinical and laboratory features of patients infected with MRSA isolates with elevated glycopeptide MICs (>1 mg/L) and with isolates that had low glycopeptide MICs (≤1 mg/L) were compared. Results A total of 104 patients infected with MRSA strains were included in this study. Male sex (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.01-6.10, p=0.048), two or more comorbidities (OR=2.48, 95% CI=1.03-6.50, p=0.044), history of MRSA infection (OR=4.91, 95% CI=1.70-14.28, p=0.003) and a longer hospital stay prior to MRSA infection (OR=2.32, 95% CI=1.05-7.85, p=0.040) were independent risk factors for high glycopeptide MICs. In MRSA infections with a teicoplanin MIC of >0.75mg/L, the microbiological and treatment failures were 46.2% (p=0.044) and 60.6% (p=0.042), respectively. Conclusion This study showed that the critical MIC value, which suggested treatment failure as well as microbiological failure in the teicoplanin-treated MRSA infections, was >0.75 mg/L rather than >1 mg/L in our study cohort. The identification of high-risk patients;for treatment failures and mortality considering gradient strip method MIC values is crucial for the effective management of MRSA infections.
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Affiliation(s)
- Elif M Sarıcaoğlu
- Department of Infectious Disease and Clinical Microbiology, Ankara University School of Medicine, Ankara, Türkiye
| | - Fügen Yörük
- Department of Infectious Disease and Clinical Microbiology, Ankara University School of Medicine, Ankara, Türkiye
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Almutairi H, Albahadel H, Alhifany AA, Aldalbahi H, Alnezary FS, Alqusi I, Mobark MA, Saeed Almutairi M. Prevalence and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) at a maternity and children hospital in Saudi Arabia: A cross-sectional study. Saudi Pharm J 2024; 32:102001. [PMID: 38439950 PMCID: PMC10909782 DOI: 10.1016/j.jsps.2024.102001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 02/20/2024] [Indexed: 03/06/2024] Open
Abstract
Background Methicillin-resistant Staphylococcus aureus (MRSA) pathogens are considered a serious global health threat, leading to increased mortality and antimicrobial resistance. Rates in Saudi Arabia remain high, necessitating continuous surveillance. This study investigates MRSA prevalence and susceptibility at a Saudi maternity and children's hospital. Method A cross-sectional study was conducted on pediatric (<18 years) and maternal patients with S. aureus infection from Jan. 2020 to March. 2022. Bacterial strains were obtained from patient's clinical specimens and was identified by standard method. The BD Phoenix™ M50 was used for antibiotic susceptibility tests and MRSA detection. Data were analysed using descriptive and inferential statistics (Chi-square test) with SPSS software. Results Out of 152 S. aureus cases, 114/152 (75 %) were pediatric and 38/152 (25 %) were maternal patients. The overall MRSA infection was 69/152 (45.4 %). Among pediatrics, 31/54 (57.4 %) MRSA cases were female; over 30/54 (56 %) were under 1 year old; and most MRSA infections were obtained from skin 29/54 (53.7 %) compared to other sites of infections (p = 0.024). Among maternal cases, 15/38 (39.5 %) were MRSA, primarily from wound infections 14/15 (93.3 %) compared to other sites of infections (p = 0.39). All MRSA isolates were sensitive to vancomycin and linezolid. While 51/60(85 %) were sensitive to Trimethoprim/ sulfamethoxazole. Conclusion This investigation found a high prevalence of MRSA among pediatrics and maternal inpatients, indicating a significant burden. All MRSA isolates were susceptible to vancomycin but demonstrated variable sensitivity to other antibiotics. These findings highlight the need for ongoing surveillance, infection control strategies, and research into alternative treatment options to combat this major public health threat.
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Affiliation(s)
- Hadiah Almutairi
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Albatin, Saudi Arabia
| | - Heyam Albahadel
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
| | - Abdullah A. Alhifany
- Pharmaceutical Practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Hind Aldalbahi
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
| | - Faris S. Alnezary
- Department of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah 41477, Saudi Arabia
| | - Ibrahim Alqusi
- Laboratory Department, Maternity and Children Hospital in Buraydah City, Ministry of Health, Qassim, Saudi Arabia
| | - Mugahid A. Mobark
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
| | - Masaad Saeed Almutairi
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
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Bahmany S, Hassanzai M, Flint RB, van Onzenoort HAW, de Winter BCM, Koch BCP. Dried blood spot analysis for the quantification of vancomycin and creatinine using liquid chromatography - tandem mass spectrometry: Method development and validation. Clin Chim Acta 2024; 553:117689. [PMID: 38052384 DOI: 10.1016/j.cca.2023.117689] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 11/30/2023] [Accepted: 12/02/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND Vancomycin is a widely used antibiotic for the treatment of gram-positive bacterial infections, especially for methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to a small therapeutic range and large inter-patient variability, therapeutic drug monitoring (TDM) of vancomycin is required to minimize toxicity and maximize treatment efficacy. Venous blood sampling is mostly applied for TDM of vancomycin, although this widely used sampling method is more invasive compared to less painful alternatives, such as the dried blood spot (DBS) method, which can be performed at home. METHOD We developed an UPLC-MS/MS method for the quantification of vancomycin and creatinine in DBS. A fast sample preparation and short analysis run time of 5.2 min were applied, which makes this method highly suitable for clinical settings. Validation was performed according to international (FDA and EMA) guidelines. RESULTS The validated concentration range was found linear for creatinine from 41.8 µmol/L to 722 µmol/L and for vancomycin from 3.8 mg/L to 76.6 mg/L (r2 > 0.990) and the inaccuracies, imprecisions, hematocrit effects, and recoveries were < 15 % for both compounds. No significant carryover effect was observed. CONCLUSION Hence, we successfully validated a quantification method for the simultaneous determination of creatinine and vancomycin in DBS.
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Affiliation(s)
- Soma Bahmany
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Moska Hassanzai
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Robert B Flint
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatric and Neonatal Intensive Care, Division of Neonatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Hein A W van Onzenoort
- Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
| | - Brenda C M de Winter
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands; CATOR: Center for Antimicrobial Treatment Optimization Rotterdam, the Netherlands
| | - Birgit C P Koch
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands; CATOR: Center for Antimicrobial Treatment Optimization Rotterdam, the Netherlands
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10
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Saseedharan S, Dubey D, Singh RK, Zirpe K, Choudhuri AH, Mukherjee DN, Gupta N, Sahasrabudhe S, Soni S, Kulkarni S, Walse P, Vora AC, Thomas J, Tayade A, Bhadarke G, Kishore K, Paliwal Y, Patil P, Reddy PK, Nagvekar V, Veeraraghavan B. Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral). Indian J Med Microbiol 2024; 47:100528. [PMID: 38228227 DOI: 10.1016/j.ijmmb.2024.100528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/22/2023] [Accepted: 01/13/2024] [Indexed: 01/18/2024]
Abstract
PURPOSE Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.
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Affiliation(s)
| | - Dilip Dubey
- Department of Critical Care, Medanta Hospital, Lucknow, India
| | | | - Kapil Zirpe
- Department of Neuro Critical Care, Ruby Hall Clinic, Grant Medical Foundation, Pune, India.
| | | | - Dip Narayan Mukherjee
- Department of Clinical Microbiology & ID, Woodlands, CMRI Hospitals and Belluview Clinic, Kolkata, India
| | - Neha Gupta
- Department of Infectious Diseases, Medanta-The Medicity & Fortis Memorial Research Institute, Gurgaon, India
| | - Shrikant Sahasrabudhe
- Department of Pulmonology and Critical Care Medicine, Medicover Hospitals, Aurangabad, India
| | - Sachin Soni
- Department of Nephrology, Dialysis and Kidney Transplantation, Medicover Hospitals, Aurangabad, India
| | - Sudhir Kulkarni
- Department of Nephrology, MGM Medical College, Aurangabad, India
| | - Prashant Walse
- Department of Critical Care, Asian Hospital, Aurangabad, India
| | | | - Jessy Thomas
- Department of Paediatrics, L H Hiranandani Hospital, Mumbai, India
| | - Ashwini Tayade
- Department of Infectious Diseases, Kingsway Hospital, Nagpur, India
| | - Girish Bhadarke
- Department of Haematology, Sankalp Specialty Hospital, Nashik, India
| | - Kamal Kishore
- Department of Pulmonary & Critical Care, Yashoda Super Speciality Hospital Kaushambi, Ghaziabad, India
| | | | - Pratik Patil
- Department of Infectious Diseases, KIMS, Secunderabad, Telangana, India
| | - Pavan Kumar Reddy
- Department of Critical Care Medicine, Care Hospitals, Banjara Hills, Hyderabad, India
| | - Vasant Nagvekar
- Department of Internal Medicine, Infectious Diseases, Lilavati Hospital & Research Centre, Bandra (W), Mumbai, India
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11
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Tomoyama A, Kobayashi N, Choe H, Ike H, Yukizawa Y, Higashihira S, Takagawa S, Kumagai K, Inaba Y. A Comparison of the Minimum Inhibitory Concentration of Antibiotics in Staphylococcus Species Isolated From Orthopedic and Respiratory Medicine Infections. Cureus 2023; 15:e49535. [PMID: 38156162 PMCID: PMC10753157 DOI: 10.7759/cureus.49535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2023] [Indexed: 12/30/2023] Open
Abstract
INTRODUCTION Antibiotic susceptibility is very important for the successful treatment of orthopedic infections, particularly for implant-related infections. While the minimum inhibitory concentrations (MICs) of Staphylococcus species were well investigated for the isolates from the respiratory tract, investigations for orthopedic pathogens are very limited. We investigated the antibiotic MIC values of Staphylococcus species isolated from orthopedic infections and compared them with those of respiratory medicine isolates used as a control. METHODS The MICs of vancomycin (VCM), arbekacin (ABK), teicoplanin (TEIC), linezolid (LZD), and rifampicin (RFP) of a total of consecutive 259 (89 orthopedic and 170 respiratory) Staphylococcus speciesisolated in our laboratory from January 2013 to July 2016 were retrospectively reviewed. Differences between the MICs of each antibiotic in orthopedic and respiratory samples were determined. RESULTS The number of methicillin-sensitive Staphylococcus aureus (MSSA) with a VCM MIC of <0.5 μg/mL among respiratory isolates was significantly higher than that among orthopedic isolates, while those with a MIC of 2 μg/mL were significantly lower (P = 0.0078). The proportion of methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates with a VCM MIC of 2 μg/mL was significantly higher in orthopedic samples than that of methicillin-resistant Staphylococcus aureus (MRSA) (P < 0.001) in respiratory isolates. The proportion of MRCNS orthopedic isolates with an RFP MIC of >2 μg/mL was significantly higher (P = 0.0058) than that of other orthopedic staphylococci. CONCLUSIONS The VCM MICs of Staphylococcus species from orthopedic infections were higher than those of respiratory samples, particularly MRCNS from implant-related samples.
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Affiliation(s)
- Akito Tomoyama
- Department of Laboratory Medicine, Yokohama City University Hospital, Yokohama, JPN
| | - Naomi Kobayashi
- Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, JPN
| | - Hyonmin Choe
- Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Yokohama, JPN
| | - Hiroyuki Ike
- Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Yokohama, JPN
| | - Yohei Yukizawa
- Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, JPN
| | - Shota Higashihira
- Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, JPN
| | - Shu Takagawa
- Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, JPN
| | - Ken Kumagai
- Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Yokohama, JPN
| | - Yutaka Inaba
- Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Yokohama, JPN
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12
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Zhang G, Zhang N, Xu J, Yang T, Yin H, Cai Y. Efficacy and safety of vancomycin for the treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis. Int J Antimicrob Agents 2023; 62:106946. [PMID: 37543121 DOI: 10.1016/j.ijantimicag.2023.106946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 06/11/2023] [Accepted: 08/01/2023] [Indexed: 08/07/2023]
Abstract
OBJECTIVES To evaluate the safety and efficacy of vancomycin with the other anti-Gram-positive bacteria antibiotics in the treatment of Staphylococcus aureus bacteraemia. METHODS We searched the PubMed, MEDLINE, Embase and Cochrane Library databases until August 2022 for studies that compared vancomycin with other antibiotic regimens for treating Staphylococcus aureus bacteraemia. Clinical and microbiological responses, adverse events, relapse rate and mortality were considered. RESULTS Fifteen randomized controlled trials and nine retrospective studies were included. The efficacy and safety data of vancomycin differed from those of the comparators group. After subgroup analysis, the differences came mainly from the trials compared with daptomycin. Compared to daptomycin, vancomycin showed a lower microbiological cure rate (OR = 0.58, 95% CI = 0.41∼0.82, I2 = 0%, P = 0.002) and clinical cure rate (OR = 0.53, 95% CI = 0.42∼0.68, I2 = 3%, P < 0.00001), as well as more adverse events (OR = 3.21, 95% CI = 1.43∼7.19, I2 = 59%, P = 0.005). CONCLUSION The efficacy of vancomycin in treating Staphylococcus aureus bacteraemia is still excellent but slightly inferior in adverse events. However, this does not affect its use as a first-line drug. Daptomycin is expected to be a better antimicrobial drug.
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Affiliation(s)
- Guanxuanzi Zhang
- Medical School of Chinese PLA, Graduate School of Chinese PLA General Hospital, Beijing, China; Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Na Zhang
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Juan Xu
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Tianli Yang
- Medical School of Chinese PLA, Graduate School of Chinese PLA General Hospital, Beijing, China; Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Hong Yin
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China.
| | - Yun Cai
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China.
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13
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Jorgensen SCJ, McIntyre M, Curran J, So M. Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals. Can J Hosp Pharm 2023; 76:203-208. [PMID: 37409147 PMCID: PMC10284285 DOI: 10.4212/cjhp.3337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
Background Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems. Objectives To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals. Methods An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations. The survey gathered data about hospital characteristics, TDM methods, inclusion criteria for patient selection, pharmacokinetic and pharmacodynamic targets, vancomycin susceptibility testing and reporting, and perceived barriers and challenges. Results In total, 120 pharmacists from 10 of the 13 provincial and territorial jurisdictions in Canada, representing 12.5% of Canadian acute care hospitals (n = 962), completed at least 90% of survey questions. The predominant TDM method was trough-based (107/119, 89.9%); another 10.1% of respondents (12/119) reported performing AUC-based TDM (with or without trough-based TDM), and 17.9% (19/106) of those not already using AUC-based TDM were considering implementing it within 1 to 2 years. Among hospitals performing trough-based TDM, 60.5% (66/109) targeted trough levels between 15 and 20 mg/L for serious infections with methicillin-resistant Staphylococcus aureus. One-quarter of the respondents using this method (27/109, 24.8%) agreed that trough-based TDM was of uncertain benefit, and about one-third (33/109, 30.3%) were neutral on this question. Multiple challenges were identified for trough-based TDM, including sub- or supra-therapeutic concentrations and collection of specimens at inappropriate times. Overall, 40.5% (47/116) of respondents agreed that AUC-based TDM was likely safer than trough-based TDM, whereas 23.3% (27/116) agreed that AUC-based TDM was likely more effective. Conclusions This survey represents a first step in developing evidence-based, standardized best practices for vancomycin TDM that are uniquely suited to the Canadian health care system.
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Affiliation(s)
- Sarah C J Jorgensen
- , PharmD, MPH, is with the Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Mark McIntyre
- , PharmD, is with the Antimicrobial Stewardship Program, Sinai Health/University Health Network, and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario
| | - Jennifer Curran
- , PharmD, is with the Antimicrobial Stewardship Program, Sinai Health/University Health Network, and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario
| | - Miranda So
- , PharmD, MPH, is with the Antimicrobial Stewardship Program, Sinai Health/University Health Network; the Leslie Dan Faculty of Pharmacy, University of Toronto; and the Toronto General Hospital Research Institute, Toronto, Ontario
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14
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Wu H, Jia C, Wang X, Shen J, Tan J, Wei Z, Wang S, Sun D, Xie Z, Luo F. The impact of methicillin resistance on clinical outcome among patients with Staphylococcus aureus osteomyelitis: a retrospective cohort study of 482 cases. Sci Rep 2023; 13:7990. [PMID: 37198265 DOI: 10.1038/s41598-023-35111-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 05/12/2023] [Indexed: 05/19/2023] Open
Abstract
This study was designed to evaluate the impact of methicillin resistance on the outcomes among patients with S. aureus osteomyelitis. We reviewed all extremity osteomyelitis patients treated in our clinic center between 2013 and 2020. All adult patients with S. aureus pathogen infection were included. Clinical outcome in terms of infection control, length of hospital stay, and complications were observed at the end of a 24-month follow-up and retrospectively analyzed between populations with/without methicillin resistance. In total, 482 osteomyelitis patients due to S. aureus were enrolled. The proportion of methicillin-resistant S. aureus (MRSA) was 17% (82) and 83% (400) of patients had Methicillin-sensitive S. aureus (MSSA). Of 482 patients, 13.7% (66) presented with infection persistence after initial debridement and antibiotic treatment (6 weeks), needed repeated debridement, 8.5% (41) had recurrence after all treatment end and a period infection cure, complications were observed in 17 (3.5%) patients (pathologic fracture; 4, nonunion; 5, amputation; 8) at final follow-up. Following multivariate analysis, we found patients with S. aureus osteomyelitis due to MRSA are more likely to develop a persistent infection (OR: 2.26; 95% CI 1.24-4.13) compared to patients with MSSA. Patients infected with MRSA also suffered more complications (8.5% vs. 2.5%, p = 0.015) and longer hospital stays (median: 32 vs. 23 days, p < 0.001). No statistically significant differences were found in recurrence. The data indicated Methicillin resistance had adverse clinical implication for infection persistence among patients with S. aureus osteomyelitis. These results will help for patients counsel and preparation for treatment.
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Affiliation(s)
- Hongri Wu
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Chao Jia
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Xiaohua Wang
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Jie Shen
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Jiulin Tan
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Zhiyuan Wei
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Shulin Wang
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China
| | - Dong Sun
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China.
| | - Zhao Xie
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China.
| | - Fei Luo
- Department of Orthopaedics, First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, The People's Republic of China.
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15
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Jaybhaye A, LG S, Dash N, Verghese V, Chacko A, Madhuri V, Palocaren T, Gahukamble A, James D, Prakash J, Rose W. Clinical Spectrum and Microbial Etiology of Bone and Joint Infections in Children: A Retrospective Analysis from South India. Am J Trop Med Hyg 2023; 108:936-941. [PMID: 37037428 PMCID: PMC10160895 DOI: 10.4269/ajtmh.22-0327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 01/06/2023] [Indexed: 04/12/2023] Open
Abstract
Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.
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Affiliation(s)
- Amol Jaybhaye
- Pediatric Infectious Diseases, Department of Pediatrics, Christian Medical College, Vellore, India
| | - Shyamsunder LG
- Department of Pediatric Orthopedics, Christian Medical College, Vellore, India
| | - Nabaneeta Dash
- Pediatric Infectious Diseases, Department of Pediatrics, Christian Medical College, Vellore, India
| | - Valsan Verghese
- Pediatric Infectious Diseases, Department of Pediatrics, Christian Medical College, Vellore, India
| | - Anila Chacko
- Pediatric Infectious Diseases, Department of Pediatrics, Christian Medical College, Vellore, India
| | - Vrisha Madhuri
- Department of Pediatric Orthopedics, Christian Medical College, Vellore, India
| | - Thomas Palocaren
- Department of Pediatric Orthopedics, Christian Medical College, Vellore, India
| | - Abhay Gahukamble
- Department of Pediatric Orthopedics, Christian Medical College, Vellore, India
| | - Deeptiman James
- Department of Pediatric Orthopedics, Christian Medical College, Vellore, India
| | - John Prakash
- Department of Clinical Microbiology, Christian Medical College, Vellore, India
| | - Winsley Rose
- Pediatric Infectious Diseases, Department of Pediatrics, Christian Medical College, Vellore, India
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16
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André C, Islam MM, Paschalis E, Bispo PJM. Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium. Cornea 2023; 42:615-623. [PMID: 36455096 PMCID: PMC10060036 DOI: 10.1097/ico.0000000000003197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/26/2022] [Accepted: 10/11/2022] [Indexed: 12/05/2022]
Abstract
PURPOSE The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). METHODS Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. RESULTS All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC) 90 0.06 μg/mL] compared with telavancin and oritavancin (MIC 90 0.12 μg/mL), whereas VAN had the lowest potency (MIC 90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. CONCLUSIONS Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.
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Affiliation(s)
- Camille André
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
- Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA; and
| | - Mohammad Mirazul Islam
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
- Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
| | - Eleftherios Paschalis
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
- Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
| | - Paulo J. M. Bispo
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
- Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA; and
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17
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Haas K, Meyer-Buehn M, von Both U, Hübner J, Schober T. Decrease in vancomycin MICs and prevalence of hGISA in MRSA and MSSA isolates from a German pediatric tertiary care center. Infection 2023; 51:583-588. [PMID: 37072604 DOI: 10.1007/s15010-023-02036-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/05/2023] [Indexed: 04/20/2023]
Abstract
PURPOSE Resistance of Staphylococcus aureus to vancomycin includes a general increase of minimal inhibitory concentrations (MIC) within the susceptible range over time (Vancomycin MIC Creep) and the presence of a subset of the bacterial population that expresses resistance (heterogeneous glycopeptide-intermediate S. aureus; hGISA). Increased MICs have been associated with adverse clinical outcomes. However, the vancomycin MIC creep is not a uniform trend suggesting the importance of regional surveys. METHODS We performed a retrospective analysis at a German pediatric tertiary care hospital. Isolates from 2002 to 2017 were selected which were newly identified methicillin-resistant S. aureus (MRSA) or samples from invasive methicillin-susceptible S. aureus (MSSA) or MRSA infections. Vancomycin and oxacillin MICs as well as GISA/hGISA were measured using MIC test strips and resistance was evaluated over time. RESULTS A total of 540 samples were tested, 200 from the early (2002-2009) and 340 from the later period (2010-2017). All samples were vancomycin susceptible, but the MIC was higher for the earlier samples as compared to the later ones (1.11 vs 0.99; p < 0.001). 14% of the samples were hGISA, GISA strains were not detected. Again, vancomycin resistance decreased over time with 28 vs. 6% hGISA (p < 0.001). There was no significant difference between MRSA and MSSA samples with respect to vancomycin MIC and hGISA prevalence. CONCLUSION This study shows a decreasing trend for both MIC values and presence of hGISA strains highlighting the importance of monitoring local susceptibilities. Vancomycin remains a first-line treatment option for suspected severe infection with Gram-positive cocci and proven infection with MRSA.
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Affiliation(s)
- Katharina Haas
- Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Melanie Meyer-Buehn
- Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Ulrich von Both
- Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
| | - Johannes Hübner
- Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Tilmann Schober
- Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
- Division of Pediatric Infectious Diseases, Montreal Children's Hospital, McGill University, McGill University Health Centre, 1001 Décarie Blvd, Montréal, QC, H4A 3J1, Canada.
- Division of Medical Microbiology, McGill University, Montreal, Canada.
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18
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André C, Schrank CL, Cheng Jaramillo AV, Mylonakis E, Wuest WM, Gilmore MS, Kim W, Bispo PJM. Antimicrobial activity of a new class of synthetic retinoid antibiotics and comparator agents against ocular staphylococci. FRONTIERS IN ANTIBIOTICS 2023; 2:1101450. [PMID: 39816665 PMCID: PMC11732056 DOI: 10.3389/frabi.2023.1101450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 03/14/2023] [Indexed: 01/18/2025]
Abstract
Objectives Antimicrobial resistance is global pandemic that poses a major threat to vision health as ocular pathogens, especially staphylococcal species, are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of a new class of synthetic retinoids in comparison to currently used antibiotics against clinically relevant ocular staphylococcal isolates. Methods Antimicrobial susceptibility testing was performed by broth microdilution for 3 novel synthetic retinoids (CD1530, CD437, and a CD437 analogue) and 7 comparator antibiotics, against a collection of 216 clinical isolates. Results CD437 MIC50 and MIC90 were 2 µg/mL for Staphylococcus aureus, and 1 µg/mL and 2 µg/mL respectively, for coagulase-negative staphylococci (CoNS). CD1530 (MIC50 = 2 µg/mL for all species) also displayed good activity with an in vitro potency slightly lower (2-fold) for S. aureus (MIC90 = 4 µg/mL) when compared to CD437. A CD437 analogue also demonstrated good in vitro activity (MIC50 = 2 µg/mL for all species) and potency (MIC90 = 2 µg/mL for MRSA and 4 µg/mL for MSSA and CoNS). In vitro potencies were similar or higher than that of comparator agents, and were not impacted by multidrug resistance phenotypes. Conclusion Our results demonstrate that synthetic retinoids display potent in vitro activity against ocular staphylococcal species, including multidrug-resistant isolates.
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Affiliation(s)
- Camille André
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Lyon, France
| | | | | | - Eleftherios Mylonakis
- Infectious Diseases Division, Warren Alpert Medical School of Brown University, Providence, RI, United States
| | - William M. Wuest
- Department of Chemistry, Emory University, Atlanta, GA, United States
| | - Michael S. Gilmore
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States
| | - Wooseong Kim
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea
| | - Paulo J. M. Bispo
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
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19
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Daffinee KE, O'Neill ET, Bleick CR, Williams G, Antoci V, Garcia D, LaPlante KL. Staphylococcal Biofilm: Penetration and bioavailability of vancomycin with or without rifampin. Diagn Microbiol Infect Dis 2023; 106:115947. [PMID: 37116243 DOI: 10.1016/j.diagmicrobio.2023.115947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 03/14/2023] [Accepted: 03/25/2023] [Indexed: 03/31/2023]
Abstract
We measured antibiotic penetration and bioavailability in staphylococcus biofilms using simulated humanized concentrations of fluorescent vancomycin plus or minus rifampin. Vancomycin percent recovery across biofilm layers was:upper = 46%, middle = 40%, and lower = 33%. Vancomycin plus rifampin was not significantly different (P = 0.65). Addition of rifampin did not improve vancomycin penetration across biofilm layers.
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Affiliation(s)
- Kathryn E Daffinee
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, USA
| | - Emily T O'Neill
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, USA; College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Callan R Bleick
- College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Geoff Williams
- Leduc Bioimaging Facility, Brown University, Division of Biology and Medicine, Providence, RI, USA
| | - Valentin Antoci
- Department of Orthopaedics, The Warren Alpert School of Medicine, Brown University, Providence, RI, USA; The Diane N. Weiss Center for Orthopaedic Trauma Research, Rhode Island Hospital, Providence, RI, USA
| | - Dioscaris Garcia
- Department of Orthopaedics, The Warren Alpert School of Medicine, Brown University, Providence, RI, USA; The Diane N. Weiss Center for Orthopaedic Trauma Research, Rhode Island Hospital, Providence, RI, USA
| | - Kerry L LaPlante
- Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, RI, USA; College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, USA.
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20
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Szemraj M, Lisiecki P, Glajzner P, Szewczyk EM. Vancomycin heteroresistance among methicillin-resistant clinical isolates S. haemolyticus, S. hominis, S. simulans, and S. warneri. Braz J Microbiol 2023; 54:159-167. [PMID: 36374479 PMCID: PMC9944261 DOI: 10.1007/s42770-022-00870-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 11/01/2022] [Indexed: 11/15/2022] Open
Abstract
Besides being an essential part of the skin microbiome, coagulase-negative staphylococci are the etiological factors of serious infections. The aim of the study was to evaluate the heteroresistance to vancomycin and the potential antimicrobial efficacy of teicoplanin and daptomycin against the multiresistant strains of S. haemolyticus, S. hominis, S. warneri, and S. simulans. The study covered 80 clinical coagulase-negative staphylococci. Teicoplanin, vancomycin, and daptomycin MICs for the tested strains were determined according to EUCAST recommendation. The vanA and vanB genes were searched. The brain heart infusion screen agar method detected vancomycin heteroresistance. The population analysis profile method and analysis of autolytic activity were applied for the strains growing on BHI containing 4 mg/L vancomycin. Seven S. haemolyticus, two S. hominis, and two S. warneri strains presented a heterogeneous resistance to vancomycin. Their subpopulations were able to grow on a medium containing 4-12 mg/L of vancomycin. Monitoring heteroresistance to peptide antibiotics, which are often the last resort in staphylococcal infections, is essential due to the severe crisis in antibiotic therapy and the lack of alternatives to treat infections with multiresistant strains. Our work highlights the selection of resistant strains and the need for more careful use of peptide antibiotics.
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Affiliation(s)
- Magdalena Szemraj
- Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszyńskiego 1, 90-235, Łódź, Poland.
| | - Paweł Lisiecki
- Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszyńskiego 1, 90-235, Łódź, Poland
| | - Paulina Glajzner
- Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszyńskiego 1, 90-235, Łódź, Poland
| | - Eligia M Szewczyk
- Department of Pharmaceutical Microbiology and Microbiological Diagnostic, Medical University of Lodz, Muszyńskiego 1, 90-235, Łódź, Poland
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21
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Chavva H, Meka Y, Long TE. Antimicrobial pharmacodynamics of vancomycin and disulfiram (Antabuse®) in Staphylococcus aureus. Front Microbiol 2023; 13:1092257. [PMID: 36687633 PMCID: PMC9854118 DOI: 10.3389/fmicb.2022.1092257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023] Open
Abstract
Introduction Intravenous vancomycin (VAN) is the primary treatment for systemic infections due to methicillin-resistant Staphylococcus aureus (MRSA). Pharmacokinetic/pharmacodynamic target (PK/PD) indices for VAN therapies are more difficult to achieve for MRSA isolates with a minimum inhibitory concentration (MIC) greater than 1 µg mL-1. This research investigated the in vitro antimicrobial PD interaction of disulfiram (DSF) with VAN as a potential adjuvant therapy for infections due to these bacteria. Methods The antimicrobial interaction was assessed by differential analysis using checkerboard titration testing, time-kill studies, flow cytometry, and the post-antibiotic effect (PAE) experiment. Ten MRSA strains with MICs ranging from 1 to >256 µg mL-1 for VAN were evaluated. A comprehensive PD assessment of the VAN/DSF interaction was performed using the VAN-intermediate (VISA) strain Mu50 (MIC 8 µg mL-1). Results The addition of DSF lowered the MIC and minimum bactericidal concentration (MBC) of VAN in either a synergistic or additive manner for the MRSA panel. Optimal bactericidal effects and suppression of VISA Mu50 growth were observed with a 4/8 µg mL-1 combination of VAN/DSF, but not the individual drugs. Flow cytometry further confirmed the enhanced killing action on a cellular level; however, the addition of DSF had an overall antagonistic effect on the PAEs for VAN. Discussion This research established that DSF exhibits additive to synergistic killing action with VAN for MRSA. Conversely, antagonism was observed on the PAE of VAN with DSF addition for the Mu50 strain. Flow cytometry further confirmed the enhanced bactericidal effect on a cellular level while revealing that DSF may counteract the muropeptide fortification mechanism against VAN in VISA.
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Affiliation(s)
- Hasitha Chavva
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States
| | - Yogesh Meka
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States
| | - Timothy E. Long
- Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, United States,Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States,*Correspondence: Timothy E. Long,
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22
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Kaur K, Khalil S, Singh NP, Dewan P, Gupta P, Shah D. Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in Hospitalized Children. Indian Pediatr 2023. [DOI: 10.1007/s13312-023-2695-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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23
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Management of bone diseases: looking at scaffold-based strategies for drug delivery. Drug Deliv Transl Res 2023; 13:79-104. [PMID: 35816230 DOI: 10.1007/s13346-022-01191-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2022] [Indexed: 12/13/2022]
Abstract
The bone tissue can regenerate itself completely and continuously; however, large-scale bone defects may overpower this self-regenerative process. Furthermore, the aging population, the increment in obesity incidence, and the sedentary lifestyles are serious risk factors for bone diseases' development which are associated with the self-regenerative process's failure, high morbidity, and mortality rates. Thus, there is an ever-growing need for strategic approaches targeting bone replacement, its remodelling, and its regeneration. Bone scaffolds have successfully been used as synthetic bone grafts for many years, yet recent bone tissue engineering strategies attempt to explore their multifunctionality by investigating them as drug delivery systems. Bone diseases' treatments can be substantially difficult due to the avascular nature of the surrounding cartilage; thus, targeted drug delivery to the bone can be advantageous: it provides local high drug concentrations and minimizes adverse effects while securing a space for new, healthy tissue growth. Despite the promising scientific progress, studies underlining bone scaffolds' use as local drug delivery systems are not abundant. Hence, this work reviews bone scaffolds' therapeutic interest for local drug delivery in five distinct bone disorders-osteomyelitis, osteoporosis, osteoarthritis, osteosarcoma, and cancer bone metastasis. Additionally, it presents the challenges of this possible therapeutic approach and its future perspectives. Albeit bone scaffolds present therapeutic benefits by acting as drug delivery systems, further pre-clinical and clinical assessments are needed to strengthen their understanding and enable research evidence translation into clinical practice. The mismatch between scientific evolution and regulatory frameworks remains one of the major future challenges.
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24
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Wagner P, Arnold J, Sheridan K. Vancomycin Loading Doses and Nephrotoxicity on Medicine Teaching Services. Int J Gen Med 2022; 15:7685-7692. [PMID: 36226308 PMCID: PMC9549902 DOI: 10.2147/ijgm.s380017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Background Infectious Disease Society of America (IDSA) guidelines recommend the usage of a loading dose when using vancomycin for seriously ill patients. While the relationship between vancomycin and nephrotoxicity is the focus of many studies, few studies have examined the relationship between vancomycin loading doses and nephrotoxicity. Methods We performed a retrospective cohort study examining vancomycin dosing for internal medicine teaching services' patients over the 2014-15 academic year at one academic medical center. We generated a list of all hospitalized patients aged 18-85 who received vancomycin and were admitted to a teaching service. Nephrotoxicity was determined by 7-day acute kidney injury (AKI) rate. Patients in the loading dose cohort were compared with those in the standard-dose cohort. Primary modeling used multivariable logistic regression with AKI as our outcome of interest. Results Four hundred and thirty-eight patients were included for analysis. The loading dose (n = 365, 83%) and standard dosing (n = 73, 17%) cohorts were not significantly different regarding demographics, GFR, nephrotoxic drug exposure, total vancomycin received, trough levels, or comorbidities and were only significantly different regarding body mass index (BMI). The 7-day AKI rate was not significantly different between the two arms (6.3% in the standard dosing arm and 8.2% in the loading dose arm, p = 0.6). Conclusion Few studies have examined the relationship between nephrotoxicity and vancomycin loading doses. The results of this study provide evidence that the use of loading doses is not significantly associated with increased 7-day AKI rate.
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Affiliation(s)
- Phillip Wagner
- Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA,Department of Internal Medicine, Johns Hopkins Hospital, Baltimore, MD, USA,Correspondence: Phillip Wagner, Johns Hopkins Hospital, 600 North Wolfe Street, Meyer 8, Room 134A, Baltimore, MD, 21287, USA, Tel +1-412-841-8522, Email
| | - Jonathan Arnold
- Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Kathleen Sheridan
- Department of Infectious Diseases, Pittsburgh Infectious Diseases, Pittsburgh, PA, USA,Correspondence: Kathleen Sheridan, Pittsburgh Infectious Disease, Pittsburgh Pennsylvania 101 Drake Street, Pittsburgh, PA, 15241, USA, Tel +1 412-347-0057, Email
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25
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Burgin DJ, Liu R, Hsieh RC, Heinzinger LR, Otto M. Investigational agents for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: progress in clinical trials. Expert Opin Investig Drugs 2022; 31:263-279. [PMID: 35129409 PMCID: PMC10988647 DOI: 10.1080/13543784.2022.2040015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 02/06/2022] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Bacteremia caused by Staphylococcus aureus is common. Cases caused by methicillin-resistant S. aureus (MRSA) are particularly formidable and often lethal. The mortality associated with MRSA bacteremia has not significantly decreased over the past couple of decades and concerns regarding efficacy and toxicity of standard therapy highlight the need for novel agents and new therapeutic approaches. AREAS COVERED This paper explores clinical trials investigating novel therapeutic approaches to S. aureus bacteremia. There is a special focus on MRSA bacteremia. Monotherapy and combination therapies and novel antimicrobials and adjunctive therapies that are only recently being established for therapeutic use are discussed. EXPERT OPINION The unfavorable safety profile of combination antimicrobial therapy in clinical trials has outweighed its benefits. Therefore, future investigation should focus on optimizing duration and de-escalation protocols. Antibody and bacteriophage lysin-based candidates have mostly been limited to safety trials, but progress with these agents is demonstrated through a lysin-based agent receiving a phase III trial. Antibiotics indicated for use in treating MRSA skin infections see continued investigation as treatments for MRSA bacteremia despite the difficulty of completing trials in this patient population. Promising agents include dalbavancin, ceftobiprole, ceftaroline, and exebacase.
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Affiliation(s)
- Dylan J. Burgin
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Ryan Liu
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Roger C. Hsieh
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Lauren R. Heinzinger
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Michael Otto
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
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26
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The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis. Microbiol Spectr 2022; 10:e0099121. [PMID: 35019708 PMCID: PMC8754111 DOI: 10.1128/spectrum.00991-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
With the increasing reports of community-acquired and nosocomial infection caused by multidrug-resistant Gram-positive pathogens, there is an urgent need to develop new antimicrobial agents with novel antibacterial mechanisms. Here, we investigated the antibacterial activity of the natural product ginkgolic acid (GA) (15:1), derived from Ginkgo biloba, and its potential mode of action against the Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus. The MIC values of GA (15:1) against clinical E. faecalis and S. aureus isolates from China were ≤4 and ≤8 μg/mL, respectively, from our test results. Moreover, GA (15:1) displayed high efficiency in biofilm formation inhibition and bactericidal activity against E. faecalis and S. aureus. During its inhibition of the planktonic bacteria, the antibacterial activity of GA (15:1) was significantly improved under the condition of abolishing iron homeostasis. When iron homeostasis was abolished, inhibition of planktonic bacteria by GA (15:1) was significantly improved. This phenomenon can be interpreted as showing that iron homeostasis disruption facilitated the disruption of the functions of ribosome and protein synthesis by GA (15:1), resulting in inhibition of bacterial growth and cell death. Genetic mutation of ferric uptake regulator (Fur) led to GA (15:1) tolerance in in vitro-induced resistant derivatives, while overexpression of Fur led to increased GA (15:1) susceptibility. Additionally, GA (15:1) significantly decreased the bacterial loads of S. aureus strain USA300 in the lung tissues of mice in a pneumonic murine model. Conclusively, this study revealed an antimicrobial mechanism of GA (15:1) involving cross talk with iron homeostasis against Gram-positive pathogens. In the future, the natural product GA (15:1) might be applied to combat infections caused by Gram-positive pathogens. IMPORTANCE The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity. However, its antibacterial mechanisms remain unclear. Our current study found that the function of ferric uptake regulator (Fur) was highly correlated with the antimicrobial activity of GA (15:1) against E. faecalis and that the antibacterial activity of GA (15:1) could be strengthened by the disruption of iron homeostasis. This study provided important insight into the mode of action of GA (15:1) against Gram-positive bacteria and suggested that GA (15:1) holds the potential to be an antimicrobial treatment option for infection caused by multidrug-resistant Gram-positive pathogens.
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Gaillard T, Dupieux-Chabert C, Butin M, Dumitrescu O, Naceur O, Bouveyron C, Martra A, Bes M, Tristan A, Vandenesch F, Lina G, Laurent F, Rasigade JP. Heterogeneous vancomycin resistance in Staphylococcus aureus does not predict development of vancomycin resistance upon vancomycin pressure. J Antimicrob Chemother 2022; 77:1032-1035. [PMID: 35022718 DOI: 10.1093/jac/dkab488] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 12/09/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND It is unclear whether Staphylococcus aureus with heterogeneous intermediate vancomycin resistance (hVISA) can develop vancomycin resistance faster than vancomycin-susceptible S. aureus (VSSA) strains. METHODS We compared the kinetics of vancomycin MIC increase for 15 days of sustained in vitro vancomycin exposure for clinical hVISA (n = 12) and VSSA (n = 24) isolates, as well as for reference strains Mu3 (hVISA) and ATCC 29213 (VSSA). Clinical isolates were categorized as hVISA using the population analysis profile method. MICs were monitored for 15 days and the rate of MIC increase under exposure, for each strain, was evaluated in a linear regression model relative to time. RESULTS All isolates acquired vancomycin resistance upon exposure. Vancomycin MICs increased faster for VSSA compared with hVISA isolates (P < 0.01). CONCLUSIONS The hVISA phenotype does not correspond to an enhanced adaptation potential to in vitro vancomycin pressure.
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Affiliation(s)
- Tiphaine Gaillard
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France
| | - Céline Dupieux-Chabert
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Marine Butin
- Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Oana Dumitrescu
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Oilida Naceur
- Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Caroline Bouveyron
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France
| | - Annie Martra
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France
| | - Michèle Bes
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Anne Tristan
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - François Vandenesch
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Gérard Lina
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Frédéric Laurent
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
| | - Jean-Philippe Rasigade
- Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France.,Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université Lyon 1, ENS de Lyon, Lyon, France
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Tuan HM, Anh NT, Quan KT, Thang NV, Huy VQ. Effect of Initial Vancomycin Dose and Creatinine Clearance on the Attainment of Target Trough Concentration in Children. Curr Pediatr Rev 2022; 18:318-325. [PMID: 35255798 DOI: 10.2174/1573396318666220307115307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/20/2021] [Accepted: 01/12/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Vancomycin is a glycopeptide antibiotic that is used to treat serious grampositive infections. However, therapeutic drug monitoring for vancomycin is not performed routinely in Vietnam in clinical practices. Monitoring of serum vancomycin concentration or trough levels is necessary to ensure the efficacy and safety of vancomycin therapy. OBJECTIVE This study aims to determine the impact of initial vancomycin dose and creatinine clearance on target trough attainment in hospitalized Vietnamese children. METHODS A prospective study with patients who received vancomycin for at least three days was conducted. Subsequently, demographic data, clinical diagnosis, vancomycin dosage, and serum creatinine levels were recorded. The vancomycin trough level was collected and creatinine clearance and adjusted vancomycin doses were calculated. RESULTS A total of 40 eligible patients were enrolled. Patients' mean age, body weight, and height were 1.4 years old, 9.8 kg, and 75.5 cm, respectively. The mean vancomycin dose was 55.83 ± 19.34 mg/kg/day. The mean creatinine clearance was 80.18 ± 29.14 ml/min. The median trough level was 11.09 (7.84 - 16.46) μg/ml. There was no significant difference in the mean initial and the adjusted vancomycin doses (p = 0.062). However, there were statistically significant differences of initial (p = 0.004) or adjusted doses (p = 0.016) between groups of creatinine clearance. The trough vancomycin concentration was not statistically significant (p = 0.406) between these groups. CONCLUSION Target trough vancomycin level may be associated with creatinine clearance but did not proportionally correspond to the vancomycin dose. Therefore, monitoring vancomycin trough levels is necessary to achieve the target trough and to ensure vancomycin efficacy and safety in treating severely infected Vietnamese children.
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Affiliation(s)
- Ha Manh Tuan
- University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Nguyen Tuan Anh
- Molecular Biomedical Center, University Medical Center, Ho Chi Minh City, Vietnam
| | - Kim Tran Quan
- American International Hospital, Thu Duc City, Vietnam
| | | | - Vu Quang Huy
- University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
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Xu Y, Wang B, Zhao H, Wang X, Rao L, Ai W, Yu J, Guo Y, Wu X, Yu F, Chen S. In Vitro Activity of Vancomycin, Teicoplanin, Linezolid and Daptomycin Against Methicillin-Resistant Staphylococcus aureus Isolates Collected from Chinese Hospitals in 2018-2020. Infect Drug Resist 2021; 14:5449-5456. [PMID: 34949928 PMCID: PMC8689657 DOI: 10.2147/idr.s340623] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/23/2021] [Indexed: 12/26/2022] Open
Abstract
Introduction Vancomycin, teicoplanin, linezolid and daptomycin are four major antibacterials used for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment. However, with the increasing failure of clinical MRSA anti-infective treatment, it is urgent to investigate the status of MRSA sensitivity to these four drugs. Methods In the present study, 407 non-duplicated MRSA isolates from 6 provinces in China were collected from January 2018 to August 2020. The minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and daptomycin were determined by broth microdilution method, and their MIC50, MIC90, and geometric mean MIC were calculated. Results All 407 MRSA strains were sensitive to these four antibacterials. MIC range of vancomycin, teicoplanin, linezolid and daptomycin was 0.25 to 2 mg/L, 0.125 to 4 mg/L, 0.25 to 4 mg/L and 0.06 to 1 mg/L, respectively. Between 2018 and 2020, there was no “MIC creep” in vancomycin, teicoplanin and daptomycin. The geometric mean MIC of linezolid was not increased, but both MIC50 and MIC90 in 2019 and 2020 MRSA isolates were higher than 2018 isolates. Conclusion All MRSA isolates remained sensitivity to vancomycin, teicoplanin, linezolid and daptomycin. The linezolid MIC50 and MIC90 increased have been found in this study.
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Affiliation(s)
- Yanlei Xu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Bingjie Wang
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Huilin Zhao
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Xinyi Wang
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Lulin Rao
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Wenxiu Ai
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Jingyi Yu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Yinjuan Guo
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Xiaocui Wu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Fangyou Yu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Shuying Chen
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
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Marathe NA, Tedesco G, Chiesa AM, Mallepally AR, Di Carlo M, Ghermandi R, Evangelisti G, Girolami M, Pipola V, Gasbarrini A. Pyogenic and Non-Pyogenic Spinal Infections: Diagnosis and Treatment. Curr Med Imaging 2021; 18:231-241. [PMID: 34789140 DOI: 10.2174/1573405617666211117143203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 08/20/2021] [Accepted: 09/15/2021] [Indexed: 11/22/2022]
Abstract
Spinal infection (SI) is an infection of vertebral bodies, intervening disc, and/or adjoining para-spinal tissue. It represents less than 10 % of all skeletal infections. There are numerous factors that predispose to developing a SI. Due to the low specificity of signs, delayed diagnosis is common. Hence, SI may be associated with poor outcomes. Diagnosis of SI must be supported by clinicopathological and radiological findings. MRI is a reliable modality of choice. Treatment options vary according to the site of the infection, disease progression, neurology, presence of instability, and general condition of the subject. Conservative treatment (orthosis/ bed-rest + antibiotics) is recommended during the early course with no/ lesser degree of neurological involvement and to medically unfit patients. Nevertheless, when conservative measures alone fail, surgical interventions must be considered. The use of concomitant antimicrobial drugs intravenously during initial duration followed by oral administration is a necessity. Controversies exist regarding the optimal duration of antimicrobial therapy, yet never given less than six weeks. Heterogeneity in clinical picture and associated co-morbidities with a range of treatment modalities are available; however, a common applicable guideline for SI does not exist. Managing SI must be tailored on a case-to-case basis.
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Affiliation(s)
| | - Giuseppe Tedesco
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Anna Maria Chiesa
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | | | - Maddalena Di Carlo
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Riccardo Ghermandi
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Gisberto Evangelisti
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Marco Girolami
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Valerio Pipola
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
| | - Alessandro Gasbarrini
- IRCCS - Istituto Ortopedico Rizzoli, Oncologic and Degenerative Spine Surgery, Bologna. Italy
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Kumaraswamy M, Wiull K, Joshi B, Sakoulas G, Kousha A, Vaaje-Kolstad G, Johannessen M, Hegstad K, Nizet V, Askarian F. Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus. Microorganisms 2021; 9:microorganisms9102055. [PMID: 34683376 PMCID: PMC8539228 DOI: 10.3390/microorganisms9102055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/17/2021] [Accepted: 09/24/2021] [Indexed: 12/02/2022] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures.
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Affiliation(s)
- Monika Kumaraswamy
- Infectious Diseases Section, VA San Diego Healthcare System, San Diego, CA 92161, USA
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
- Collaborative to Halt Antibiotic Resistant Microbes (CHARM), University of California San Diego, La Jolla, CA 92093, USA;
- Correspondence: (M.K.); (F.A.)
| | - Kamilla Wiull
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1433 Ås, Norway; (K.W.); (G.V.-K.)
| | - Bishnu Joshi
- Research Group for Host-Microbe Interactions, UiT-The Arctic University of Norway, 9037 Tromsø, Norway; (B.J.); (M.J.); (K.H.)
| | - George Sakoulas
- Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; (G.S.); (A.K.)
| | - Armin Kousha
- Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; (G.S.); (A.K.)
| | - Gustav Vaaje-Kolstad
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1433 Ås, Norway; (K.W.); (G.V.-K.)
| | - Mona Johannessen
- Research Group for Host-Microbe Interactions, UiT-The Arctic University of Norway, 9037 Tromsø, Norway; (B.J.); (M.J.); (K.H.)
| | - Kristin Hegstad
- Research Group for Host-Microbe Interactions, UiT-The Arctic University of Norway, 9037 Tromsø, Norway; (B.J.); (M.J.); (K.H.)
- Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, University Hospital of North-Norway, 9038 Tromsø, Norway
| | - Victor Nizet
- Collaborative to Halt Antibiotic Resistant Microbes (CHARM), University of California San Diego, La Jolla, CA 92093, USA;
- Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; (G.S.); (A.K.)
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA
| | - Fatemeh Askarian
- Research Group for Host-Microbe Interactions, UiT-The Arctic University of Norway, 9037 Tromsø, Norway; (B.J.); (M.J.); (K.H.)
- Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; (G.S.); (A.K.)
- Correspondence: (M.K.); (F.A.)
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Vilela MJC, Colaço BJA, Ventura J, Monteiro FJM, Salgado CL. Translational Research for Orthopedic Bone Graft Development. MATERIALS (BASEL, SWITZERLAND) 2021; 14:4130. [PMID: 34361324 PMCID: PMC8348134 DOI: 10.3390/ma14154130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 11/17/2022]
Abstract
Designing biomaterials for bone-substitute applications is still a challenge regarding the natural complex structure of hard tissues. Aiming at bone regeneration applications, scaffolds based on natural collagen and synthetic nanohydroxyapatite were developed, and they showed adequate mechanical and biological properties. The objective of this work was to perform and evaluate a scaled-up production process of this porous biocomposite scaffold, which promotes bone regeneration and works as a barrier for both fibrosis and the proliferation of scar tissue. The material was produced using a prototype bioreactor at an industrial scale, instead of laboratory production at the bench, in order to produce an appropriate medical device for the orthopedic market. Prototypes were produced in porous membranes that were e-beam irradiated (the sterilization process) and then analysed by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), dynamic mechanical analysis (DMA), cytotoxicity tests with mice fibroblasts (L929), human osteoblast-like cells (MG63) and human MSC osteogenic differentiation (HBMSC) with alkaline phosphatase (ALP) activity and qPCR for osteogenic gene expression. The prototypes were also implanted into critical-size bone defects (rabbits' tibia) for 5 and 15 weeks, and after that were analysed by microCT and histology. The tests performed for the physical characterization of the materials showed the ability of the scaffolds to absorb and retain water-based solvents, as well as adequate mechanical resistance and viscoelastic properties. The cryogels had a heteroporous morphology with microporosity and macroporosity, which are essential conditions for the interaction between the cells and materials, and which consequently promote bone regeneration. Regarding the biological studies, all of the studied cryogels were non-cytotoxic by direct or indirect contact with cells. In fact, the scaffolds promoted the proliferation of the human MSCs, as well as the expression of the osteoblastic phenotype (osteogenic differentiation). The in vivo results showed bone tissue ingrowth and the materials' degradation, filling the critical bone defect after 15 weeks. Before and after irradiation, the studied scaffolds showed similar properties when compared to the results published in the literature. In conclusion, the material production process upscaling was optimized and the obtained prototypes showed reproducible properties relative to the bench development, and should be able to be commercialized. Therefore, it was a successful effort to harness knowledge from the basic sciences to produce a new biomedical device and enhance human health and wellbeing.
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Affiliation(s)
- Maria J. C. Vilela
- Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal; (M.J.C.V.); (F.J.M.M.)
- Instituto Nacional de Engenharia Biomédica (INEB), 4200-135 Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal
| | - Bruno J. A. Colaço
- Department of Animal Science, CECAV—Animal and Veterinary Research Centre UTAD, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal;
| | | | - Fernando J. M. Monteiro
- Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal; (M.J.C.V.); (F.J.M.M.)
- Instituto Nacional de Engenharia Biomédica (INEB), 4200-135 Porto, Portugal
- Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal
| | - Christiane L. Salgado
- Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal; (M.J.C.V.); (F.J.M.M.)
- Instituto Nacional de Engenharia Biomédica (INEB), 4200-135 Porto, Portugal
- Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal
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Hines KM, Shen T, Ashford NK, Waalkes A, Penewit K, Holmes EA, McLean K, Salipante SJ, Werth BJ, Xu L. Occurrence of cross-resistance and β-lactam seesaw effect in glycopeptide-, lipopeptide- and lipoglycopeptide-resistant MRSA correlates with membrane phosphatidylglycerol levels. J Antimicrob Chemother 2021; 75:1182-1186. [PMID: 32016379 DOI: 10.1093/jac/dkz562] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/14/2019] [Accepted: 12/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Glycopeptides (GPs), lipopeptides (LPs) and lipoglycopeptides (LGPs) are related antimicrobials important for the management of invasive MRSA infections. Cross-resistance among these antibiotics in MRSA is well documented, as is the observation that susceptibility of MRSA to β-lactams increases as susceptibility to GPs and LPs decreases (i.e. the seesaw effect). Efforts to understand the relationship between GP/LP/LGP cross-resistance and the seesaw effect have focused on the PBPs, but the role of lipid metabolism has not been investigated. OBJECTIVES Since the cell membrane is structurally and metabolically integrated with the cell wall and anchors associated proteins, including PBPs, we examined the relationship between membrane lipid composition and the phenomena of cross-resistance among GPs/LPs/LGPs and the β-lactam seesaw effect. METHODS We selected for daptomycin, vancomycin and dalbavancin resistance using the USA300 strain JE2 and evaluated the resulting mutants by WGS, MS-based lipidomics and antimicrobial susceptibility testing to assess the relationship between membrane composition, cross-resistance, and the seesaw effect. RESULTS We observed cross-resistance to GPs/LPs/LGPs among the selected strains and the seesaw effect against various β-lactams, depending on the PBP targets of the particular β-lactam. We found that modification of membrane composition occurs not only in daptomycin-selected strains, but also vancomycin- and dalbavancin-selected strains. Significantly, we observed that the abundance of most phosphatidylglycerols positively correlates with MICs of GPs/LPs/LGPs and negatively correlates with the MICs of β-lactams. CONCLUSIONS These studies demonstrate a major association between membrane remodelling, cross-resistance and the seesaw effect.
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Affiliation(s)
- Kelly M Hines
- Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
| | - Tianwei Shen
- Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
| | | | - Adam Waalkes
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
| | - Kelsi Penewit
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
| | - Elizabeth A Holmes
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
| | - Kathryn McLean
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
| | - Stephen J Salipante
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
| | - Brian J Werth
- Department of Pharmacy, University of Washington, Seattle, WA, USA
| | - Libin Xu
- Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
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New Quinone Antibiotics against Methicillin-Resistant S. aureus. Antibiotics (Basel) 2021; 10:antibiotics10060614. [PMID: 34063846 PMCID: PMC8224091 DOI: 10.3390/antibiotics10060614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/10/2021] [Accepted: 05/18/2021] [Indexed: 01/21/2023] Open
Abstract
There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC® 43300), methicillin-sensitive S. aureus (ATCC® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.
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Urie R, McBride M, Ghosh D, Fattahi A, Nitiyanandan R, Popovich J, Heys JJ, Kilbourne J, Haydel SE, Rege K. Antimicrobial laser-activated sealants for combating surgical site infections. Biomater Sci 2021; 9:3791-3803. [PMID: 33876069 PMCID: PMC9617567 DOI: 10.1039/d0bm01438a] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.
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Affiliation(s)
- Russell Urie
- Chemical Engineering Program, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287, USA.
| | - Michelle McBride
- Biodesign Institute Center for Bioelectronics and Biosensors, Arizona State University, Tempe, AZ 85287, USA.
| | - Deepanjan Ghosh
- Biological Design Graduate Program, Arizona State University, Tempe, AZ 85287, USA
| | - Ali Fattahi
- Chemical Engineering Program, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287, USA.
| | | | - John Popovich
- Biodesign Institute Center for Bioelectronics and Biosensors, Arizona State University, Tempe, AZ 85287, USA.
| | - Jeffrey J Heys
- Chemical and Biological Engineering Department, Montana State University, Bozeman, MT 59717, USA
| | - Jacquelyn Kilbourne
- Department of Animal Care and Technologies, Arizona State University, Tempe, AZ 85287, USA
| | - Shelley E Haydel
- Biodesign Institute Center for Bioelectronics and Biosensors, Arizona State University, Tempe, AZ 85287, USA. and School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA
| | - Kaushal Rege
- Chemical Engineering Program, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287, USA. and Biological Design Graduate Program, Arizona State University, Tempe, AZ 85287, USA
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Song X, Zeng M, Wu Y, Pan Y. Competence Mining of Vancomycin (VAN) in the Management of Infections Due to Bacterial Strains With High VAN Minimum Inhibitory Concentrations (MICs): A Novel Dosing Strategy Based on Pharmacokinetic/Pharmacodynamic Modeling. Front Microbiol 2021; 12:649757. [PMID: 33967986 PMCID: PMC8100448 DOI: 10.3389/fmicb.2021.649757] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 03/30/2021] [Indexed: 11/13/2022] Open
Abstract
The increasing emergence of bacterial strains with high VAN MICs (BSH–VAN–M), such as Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus bovis, results in growing concern that VAN is not effective against these isolates. Due to the limited data on VAN against BSH–VAN–M and the application limits of drugs currently considered to be effective for BSH–VAN–M, exploration of “new usages for old drugs” is reasonable to improve and maximize the efficacy of existing antibiotics. This study aimed to construct a novel dosing strategy to mine the competence of VAN in the management of BSH–VAN–M infections. Herein, we optimized the traditional intermittent i.v. infusion (TIII) method to create an optimal two-step infusion (OTSI). With pharmacokinetic (PK)/pharmacodynamic (PD) modeling at the targeted ratio of the daily area under the concentration-time curve (AUC0–24) to the minimum inhibitory concentration (MIC) (AUC0–24/MIC) of 400, we used Monte Carlo simulations to evaluate the efficacy of 25 VAN regimens (including 15 OTSI regimens and 10 TIII regimens with daily doses of up to 6 g) to treat pneumonia, meningitis, sternal osteomyelitis, mastitis, pleuritis, bacteremia, and bacterial pericarditis resulting from isolates with MICs of ≤64 mg/L and to the current E. faecalis, E. faecium, S. aureus, S. epidermidis, and S. bovis populations with a pooled MIC distribution. Our data indicated that 4 g/day VAN, with an OTSI but not a TIII, for mastitis, pleuritis, bacteremia, and bacterial pericarditis due to isolates with MICs of ≤4 mg/L or to the current E. faecalis, S. aureus, S. epidermidis, and S. bovis populations achieved the desired PK/PD exposure at the AUC0–24/MIC target of 400. This study suggests the superiority and feasibility of OTSI relative to TIII for the competence mining of VAN against BSH–VAN–M from the perspective of PK/PD and provides a new resource for understanding how PK/PD modeling shapes the performance of VAN to meet the growing challenges of BSH–VAN–M infections.
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Affiliation(s)
- Xiangqing Song
- Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Meizi Zeng
- Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yi Wu
- Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yong Pan
- Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
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The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. Pathogens 2021; 10:pathogens10020165. [PMID: 33557078 PMCID: PMC7913839 DOI: 10.3390/pathogens10020165] [Citation(s) in RCA: 357] [Impact Index Per Article: 89.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/21/2021] [Accepted: 02/01/2021] [Indexed: 12/19/2022] Open
Abstract
Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.
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Lopes SP, Jorge P, Sousa AM, Pereira MO. Discerning the role of polymicrobial biofilms in the ascent, prevalence, and extent of heteroresistance in clinical practice. Crit Rev Microbiol 2021; 47:162-191. [PMID: 33527850 DOI: 10.1080/1040841x.2020.1863329] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Antimicrobial therapy is facing a worrisome and underappreciated challenge, the phenomenon of heteroresistance (HR). HR has been gradually documented in clinically relevant pathogens (e.g. Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia spp., Acinetobacter baumannii, Klebsiella pneumoniae, Candida spp.) towards several drugs and is believed to complicate the clinical picture of chronic infections. This type of infections are typically mediated by polymicrobial biofilms, wherein microorganisms inherently display a wide range of physiological states, distinct metabolic pathways, diverging refractory levels of stress responses, and a complex network of chemical signals exchange. This review aims to provide an overview on the relevance, prevalence, and implications of HR in clinical settings. Firstly, related terminologies (e.g. resistance, tolerance, persistence), sometimes misunderstood and overlapped, were clarified. Factors generating misleading HR definitions were also uncovered. Secondly, the recent HR incidences reported in clinically relevant pathogens towards different antimicrobials were annotated. The potential mechanisms underlying such occurrences were further elucidated. Finally, the link between HR and biofilms was discussed. The focus was to recognize the presence of heterogeneous levels of resistance within most biofilms, as well as the relevance of polymicrobial biofilms in chronic infectious diseases and their role in resistance spreading. These topics were subject of a critical appraisal, gaining insights into the ascending clinical implications of HR in antimicrobial resistance spreading, which could ultimately help designing effective therapeutic options.
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Affiliation(s)
- Susana Patrícia Lopes
- CEB - Centre of Biological Engineering, LIBRO - Laboratory of Research in Biofilms Rosário Oliveira, University of Minho, Braga, Portugal
| | - Paula Jorge
- CEB - Centre of Biological Engineering, LIBRO - Laboratory of Research in Biofilms Rosário Oliveira, University of Minho, Braga, Portugal
| | - Ana Margarida Sousa
- CEB - Centre of Biological Engineering, LIBRO - Laboratory of Research in Biofilms Rosário Oliveira, University of Minho, Braga, Portugal
| | - Maria Olívia Pereira
- CEB - Centre of Biological Engineering, LIBRO - Laboratory of Research in Biofilms Rosário Oliveira, University of Minho, Braga, Portugal
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39
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Yoon JG, Huh K, Sohn YM, Park HJ, Na SJ, Jeon K. Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia. J Thorac Dis 2021; 13:768-777. [PMID: 33717549 PMCID: PMC7947502 DOI: 10.21037/jtd-20-2243] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background Vancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25–30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome. Methods A retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality. Results A total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% vs. 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 vs. 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not. Conclusions Initial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.
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Affiliation(s)
- Jin Gu Yoon
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - You Min Sohn
- Department of Pharmaceutical Services, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyo Jung Park
- Department of Pharmaceutical Services, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Soo Jin Na
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyeongman Jeon
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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40
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Sidders AE, Radlinski LC, Rowe SE, Conlon BP. Stimulating Aminoglycoside Uptake to Kill Staphylococcus aureus Persisters. Methods Mol Biol 2021; 2357:223-236. [PMID: 34590262 DOI: 10.1007/978-1-0716-1621-5_15] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Aminoglycosides are bactericidal drugs which require a proton motive force (PMF) for uptake into the bacterial cell. Low energy cells, such as persisters, maintain a PMF below the threshold for drug uptake and are tolerant to aminoglycosides. In this chapter, we discuss mechanisms to target the bacterial membrane and stimulate aminoglycoside uptake to kill Staphylococcus aureus persisters.
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Affiliation(s)
- Ashelyn E Sidders
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Lauren C Radlinski
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Sarah E Rowe
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Brian P Conlon
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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41
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Arshad F, Saleem S, Jahan S, Tahir R. Assessment of Vancomycin MIC Creep Phenomenon in Methicillin-Resistant Staphylococcus aureus isolates in a Tertiary Care Hospital of Lahore. Pak J Med Sci 2020; 36:1505-1510. [PMID: 33235565 PMCID: PMC7674903 DOI: 10.12669/pjms.36.7.3273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective: To assess vancomycin MIC creep phenomenon in methicillin-resistant Staphylococcus aureus isolated from clinical specimens. Methods: This descriptive study was conducted in Microbiology department of University of Health Sciences, Lahore from January 2016- December 2019. In this study, vancomycin MICs were revealed by E test method for clinical MRSA strains. For the final evaluation, a single isolate from each patient was taken. The reported vancomycin MICs results were used and the values were not rounded up to the next upward value. For every study year, MIC50, MIC90, median and geometrical mean MIC, percentages of susceptible and resistant strains were calculated. Results: A total of 352 MRSA strains were isolated out of 2704 staphylococcal isolates. Our study showed elevated vancomycin MIC among MRSA isolates. The majority of isolates showed MIC values ≥1.5µg/ml. MIC50, MIC 90 was constant throughout four years period. However, geometric mean MIC increased gradually during the study period. The MIC greater than base year median was overall 17.3%. A complete shift can be observed between MIC “1.0” and “2.0” the percent of cases with MIC “1.0” decreased and with MIC “2.0” increased over time crossing each other in 2017. Conclusion: Vancomycin MIC creep was identified in clinical isolates of MRSA, during four years of study period. Even though there is an absence of VISA and VRSA strains; this significant increase in vancomycin MIC trend is indeed worrying for the clinicians about the threat of potential failure of treatment in MRSA infections.
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Affiliation(s)
- Faiqa Arshad
- Dr. Faiqa Arshad Ph.D. Scholar. Department of Microbiology, University of Health Sciences, Lahore, Pakistan
| | - Sidrah Saleem
- Dr. Sidrah Saleem, MBBS, M.Phil., PhD (Microbiology), Professor & Head, Department of Microbiology, University of Health Sciences, Lahore, Pakistan
| | - Shah Jahan
- Dr. Shah Jahan, PhD (Molecular Biology), Associate Professor, Department of Immunology, University of Health Sciences, Lahore, Pakistan
| | - Romeeza Tahir
- Dr. Romeeza Tahir, M.Sc., M.Phil., PhD (Immunology) Assistant Professor, Department of Immunology, University of Health Sciences, Lahore, Pakistan
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Ullah K, Khan SA, Mannan A, Khan R, Murtaza G, Yameen MA. Enhancing the Antibacterial Activity of Erythromycin with Titanium Dioxide Nanoparticles against MRSA. Curr Pharm Biotechnol 2020; 21:948-954. [PMID: 31994459 DOI: 10.2174/1389201021666200128124142] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 09/13/2019] [Accepted: 12/11/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND Staphylococcus aureus (S. aureus) is the most common infectious agent in the community and hospitals. Infections with S. aureus are now becoming difficult to be treated by using conventional antibiotics due to its emerging methicillin-resistant S. aureus (MRSA) strain. OBJECTIVE In the present study, MRSA was isolated from clinical samples and evaluated for resistance against different antibiotics, TiO2 nanoparticles, and their combinations. METHODS Clinical samples were collected from Ayub Medical Complex (AMC), Abbottabad, Pakistan, and identified by different biochemical tests and polymerase chain reactions (PCR). Kirby-Bauer disk diffusion method was performed to evaluate antimicrobial susceptibility. Minimum Inhibitory Concentration (MIC) of ampicillin, ciprofloxacin, erythromycin, and vancomycin was found out by agar dilution method while the broth dilution method was used for the MIC of TiO2 nanoparticles and their combinations with erythromycin. RESULTS All 13/100 (13%) MRSA were successfully identified. All isolates were susceptible to quinupristin/ dalfopristin, teicoplanin, and vancomycin, while the highest resistance was seen with erythromycin, penicillin, and tetracycline. MIC showed high resistance against ampicillin (0.25-512 mg/L) and erythromycin (0.25-1024 mg/L). CONCLUSION The MIC value of 2 mM TiO2 nanoparticles was found to be the most effective concentration after 12 h of incubation, while the combination of erythromycin with 3 mM TiO2 nanoparticles was found to be more potent which significantly lowered down the MIC of erythromycin to 2-16 mg/L.
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Affiliation(s)
- Kaleem Ullah
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
| | - Shujaat A Khan
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
| | - Abdul Mannan
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
| | - Romana Khan
- Department of Environmental Sciences, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
| | - Ghulam Murtaza
- Department of Pharmacy, COMSATS University Islamabad, Lahore Campus 54000, Pakistan
| | - Muhammad A Yameen
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
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43
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Yadegarynia D, Tehrani S, Nasiri M. Community- and Health Care-Associated Methicillin-Resistant Staphylococcus aureus Infection in Tehran, Iran: Comparison of drug resistance and virulence determinants. Infect Disord Drug Targets 2020; 21:553-557. [PMID: 32957895 DOI: 10.2174/1871526520999200918125432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 07/14/2020] [Accepted: 07/19/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) can cause serious infections not only in hospitals but also in the community. The present study was aimed to characterize drug resistance and virulence determinants of community-associated (CA) MRSA isolate compared with healthcare-associated (HA) MRSA. MATERIALS AND METHODS A total of 44 patients with HA-MRSA and 11 patients with CA-MRSA infection (median age, 72 years) were included. The clinical isolates of MRSA were subjected to molecular analysis of virulence genes and drug susceptibility testing. RESULTS Panton-Valentine leucocidin (PVL) exotoxin and toxic shock syndrome toxin (TSST) genes were disproportionately distributed between CA- and HA-isolates. PVL genes were more likely to be found among CA-isolates (36.4%) than HAisolates (18.2). TSST genes were identified in only 2 CA-MRSA isolates tested (18.2%) compared with 9 HA-isolate (20.5%). Exfoliative toxin-b gene was negative in all isolates, however, one HA-isolate was positive for exfoliative toxin-a. mec-A gene was present in all clinical isolates. CA-isolates were more likely to be susceptible to trimethoprimsulfamethoxazole and vancomycin compared with HA-isolates. Vancomycin-intermediate resistance was found in 2 HAisolates. All clinical isolates were also resistant to clindamycin. CONCLUSIONS CA- and HA- MRSA isolates are epidemiologically and microbiologically distinct. Thus, the strategies to prevent and treat these infections would be different. Patients with CA- and HA-MRSA infections should be treated effectively and receive follow-up evaluation to ensure resolution of their infection. Surveillance studies should be conducted to determine the extent of CA- and HA-MRSA dissemination in Iran.
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Affiliation(s)
- Davood Yadegarynia
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Shabnam Tehrani
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Maryam Nasiri
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
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Jacqz-Aigrain E, Leroux S, Thomson AH, Allegaert K, Capparelli EV, Biran V, Simon N, Meibohm B, Lo YL, Marques R, Peris JE, Lutsar I, Saito J, Nakamura H, van den Anker JN, Sharland M, Zhao W. Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. J Antimicrob Chemother 2020; 74:2128-2138. [PMID: 31049551 DOI: 10.1093/jac/dkz158] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/26/2019] [Accepted: 03/16/2019] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. METHODS A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates. RESULTS A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0-24 target earlier than a standard 'Blue Book' dosage regimen in >89% of the treated patients. CONCLUSIONS The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.
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Affiliation(s)
- Evelyne Jacqz-Aigrain
- Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France.,Clinical Investigation Center CIC1426, Hôpital Robert Debré, Paris, France.,University Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Stéphanie Leroux
- Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France.,Clinical Investigation Center CIC1426, Hôpital Robert Debré, Paris, France.,Division of Neonatology, Department of Child and Adolescent Medicine, CHU de Rennes, Rennes, France
| | - Alison H Thomson
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.,Pharmacy Department, Glasgow Royal Infirmary, Glasgow, UK
| | - Karel Allegaert
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Intensive Care, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Edmund V Capparelli
- Pediatric Pharmacology and Drug Discovery, University of California, San Diego, CA, USA
| | - Valérie Biran
- Neonatal Intensive Care Unit, Hôpital Robert Debré, Paris, France
| | - Nicolas Simon
- Department of Pharmacology, Hôpital de la Timone, APHM, Université de la Méditerranée, Marseille, France.,Service de Pharmacologie Clinique, Hôpital Sainte marguerite, CAP-TV, 13274 Marseille, France.,Aix Marseille University, INSERM, IRD, SESSTIM, Marseille, France
| | - Bernd Meibohm
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Yoke-Lin Lo
- Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.,School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Remedios Marques
- Department of Pharmacy Services, La Fe Hospital, Valencia, Spain
| | - José-Esteban Peris
- Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain
| | - Irja Lutsar
- Institute of Medical Microbiology, University of Tartu, Tartu, Estonia
| | - Jumpei Saito
- Department of Pharmacy, National Children's Hospital National Center for Child Health and Development, Tokyo, Japan
| | - Hidefumi Nakamura
- Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, Tokyo, Japan
| | - Johannes N van den Anker
- Pharmacy Department, Glasgow Royal Infirmary, Glasgow, UK.,Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.,Departments of Pediatrics, Pharmacology & Physiology, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA.,Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, Basel, Switzerland
| | - Mike Sharland
- Paediatric Infectious Disease Unit, St George's Hospital, London, UK
| | - Wei Zhao
- Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France.,Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.,Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China
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Timsit JF, Baleine J, Bernard L, Calvino-Gunther S, Darmon M, Dellamonica J, Desruennes E, Leone M, Lepape A, Leroy O, Lucet JC, Merchaoui Z, Mimoz O, Misset B, Parienti JJ, Quenot JP, Roch A, Schmidt M, Slama M, Souweine B, Zahar JR, Zingg W, Bodet-Contentin L, Maxime V. Expert consensus-based clinical practice guidelines management of intravascular catheters in the intensive care unit. Ann Intensive Care 2020; 10:118. [PMID: 32894389 PMCID: PMC7477021 DOI: 10.1186/s13613-020-00713-4] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 07/06/2020] [Indexed: 12/15/2022] Open
Abstract
The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emergency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Intensivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheter-related infections’ prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2− adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed definitions, and therapeutic strategies.
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Affiliation(s)
- Jean-François Timsit
- APHP/Hopital Bichat-Medical and Infectious Diseases ICU (MI2), 46 rue Henri Huchard, 75018, Paris, France.,UMR 1137-IAME Team 5-DeSCID: Decision SCiences in Infectious Diseases, Control and Care Inserm/Université de Paris, Sorbonne Paris Cité, 75018, Paris, France
| | - Julien Baleine
- Department of Neonatal Medicine and Pediatric Intensive Care, Arnaud de Villeneuve University Hospital, 371 Avenue Doyen G Giraud, 34295, Montpellier Cedex 5, France
| | - Louis Bernard
- Infectious Diseases Unit, University Hospital Tours, Nîmes 2 Boulevard, 37000, Tours, France
| | - Silvia Calvino-Gunther
- CHU Grenoble Alpes, Réanimation Médicale Pôle Urgences Médecine Aiguë, 38000, Grenoble, France
| | - Michael Darmon
- Medical ICU, Saint-Louis University Hospital, AP-HP, Paris, France
| | - Jean Dellamonica
- Centre Hospitalier Universitaire de Nice, Médecine Intensive Réanimation, Archet 1, UR2CA Unité de Recherche Clinique Côte d'Azur, Université Cote d'Azur, Nice, France
| | - Eric Desruennes
- Clinique d'anesthésie pédiatrique, Hôpital Jeanne-de-Flandre, avenue Eugène-Avinée, CHU Lille, 59000, Lille, France.,Unité accès vasculaire, Centre Oscar Lambret, 3 rue Frédéric Combemale, 59000, Lille, France
| | - Marc Leone
- Anesthésie Réanimation, Hôpital Nord, 13015, Marseille, France
| | - Alain Lepape
- Service d'Anesthésie et de Réanimation, Hospices Civils de Lyon, Groupement Hospitalier Sud, Lyon, France.,UMR CNRS 5308, Inserm U1111, Laboratoire des Pathogènes Émergents, Centre International de Recherche en Infectiologie, Lyon, France
| | - Olivier Leroy
- Medical ICU, Chatilliez Hospital, Tourcoing, France.,U934/UMR3215, Institut Curie, PSL Research University, 75005, Paris, France
| | - Jean-Christophe Lucet
- AP-HP, Infection Control Unit, Bichat-Claude Bernard University Hospital, 46 rue Henri Huchard, 75877, Paris Cedex, France.,INSERM IAME, U1137, Team DesCID, University of Paris, Paris, France
| | - Zied Merchaoui
- Pediatric Intensive Care, Paris South University Hospitals AP-HP, Le Kremlin Bicêtre, France
| | - Olivier Mimoz
- Services des Urgences Adultes and SAMU 86, Centre Hospitalier Universitaire de Poitiers, 86021, Poitiers, France.,Université de Poitiers, Poitiers, France.,Inserm U1070, Poitiers, France
| | - Benoit Misset
- Department of Intensive Care, Sart-Tilman University Hospital, and University of Liège, Liège, Belgium
| | - Jean-Jacques Parienti
- Department of Biostatistics and Clinical Research and Department of Infectious Diseases, Caen University Hospital, 14000, Caen, France.,EA2656 Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0) UNICAEN, CHU Caen Medical School Université Caen Normandie, Caen, France
| | - Jean-Pierre Quenot
- Department of Intensive Care, François Mitterrand University Hospital, Dijon, France.,Lipness Team, INSERM Research Center LNC-UMR1231 and LabExLipSTIC, University of Burgundy, Dijon, France.,INSERM CIC 1432, Clinical Epidemiology, University of Burgundy, Dijon, France
| | - Antoine Roch
- Assistance Publique - Hôpitaux de Marseille, Hôpital Nord, Service des Urgences, 13015, Marseille, France.,Centre d'Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279, Faculté de médecine, Aix-Marseille Université, 13005, Marseille, France
| | - Matthieu Schmidt
- Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpêtrière Hospital, Medical Intensive Care Unit, 75651, Paris, France.,INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Medical Intensive Care Unit, Sorbonne Universités, 75651, Paris Cedex 13, France
| | - Michel Slama
- Medical Intensive Care Unit, CHU Sud Amiens, Amiens, France
| | - Bertrand Souweine
- Medical ICU, Gabriel-Montpied University Hospital, Clermont-Ferrand, France
| | - Jean-Ralph Zahar
- IAME, UMR 1137, Université Paris 13, Sorbonne Paris Cité, Paris, France.,Service de Microbiologie Clinique et Unité de Contrôle et de Prévention Du Risque Infectieux, Groupe Hospitalier Paris Seine Saint-Denis, AP-HP, 125 Rue de Stalingrad, 93000, Bobigny, France
| | - Walter Zingg
- Infection Control Programme and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Laetitia Bodet-Contentin
- Medical Intensive Care Unit, INSERM CIC 1415, CRICS-TriGGERSep Network, CHRU de Tours and Université de Tours, Tours, France
| | - Virginie Maxime
- Surgical and Medical Intensive Care Unit Hôpital, Raymond Poincaré, 9230, Garches, France.
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Bacterial communities in the natural and supplemental nests of an endangered ecosystem engineer. Ecosphere 2020. [DOI: 10.1002/ecs2.3239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
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Adeoye-Isijola M, Olajuyigbe O, Adebola K, Coopoosamy R, Afolayan A. Vancomycin intermediate resistant Staphylococcus aureus in the nasal cavity of asymptomatic individuals: a potential public health challenge. Afr Health Sci 2020; 20:1109-1117. [PMID: 33402955 PMCID: PMC7751515 DOI: 10.4314/ahs.v20i3.12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background The potential of transmitting multidrug resistant Staphylococcus aureus from asymptomatic individuals to healthy individuals could constitute a great challenge to antimicrobial therapy. Methods The antibiograms of the S. aureus from asymptomatic individuals were determined by disk diffusion and agar dilution assay techniques with different antibiotics and vancomycin. Results Of the 152 S. aureus isolated, (59)38.8% isolates were multi-drug resistant strains. Streptomycin was the most effective and inhibited (135)88.82% of the isolates while ceftazidime inhibited (24)15.8% of the isolates. While (82)54.0% of the isolates inhibited by cefuroxime had resistant colonies within their inhibition zones (Rc) and ofloxacin inhibited (100)65.8% of the isolates without having resistant colonies within the inhibition zones, ceftazidime inhibited (7)4.6% of the isolates with resistant colonies within the inhibition zones. Subjecting the isolates to vancomycin showed that (27)17.8% were resistant to 2 µg/ml, (43)28.3% were resistant to 4 µg/ml and (27)17.8% of the isolates were simultaneously resistant to both concentrations of vancomycin. Although (100)65.8% of the isolates had MARindex ≥0.2, (52)34.2% of the isolates had MARindex ≤ 0.2 and (65)428% of the isolates were considered multidrug resistant strains. Conclusion The isolation of multi-drug and vancomycin intermediate resistant strains of S. aureus in high percentage, in this study, presents a great threat to clinicians and general populace. The vancomycin intermediate resistant S. aureus (VISA) in asymptomatic individuals could be a critical concern to the therapeutic dilemma to be added to the presence of multi-drug resistance. A more sustainable therapy must be in place to prevent its dissemination or the outbreak of its infection.
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Affiliation(s)
- Morenike Adeoye-Isijola
- Department of Microbiology, School of Science & Technology, Babcock University, PMB 4005, Ilisan-Remo, Ogun State, Nigeria
| | - Olufunmiso Olajuyigbe
- Department of Microbiology, School of Science & Technology, Babcock University, PMB 4005, Ilisan-Remo, Ogun State, Nigeria
- Department of Nature Conservation, Faculty of Natural Sciences, Mangosuthu University of Technology, P.O. Box 12363, Jacobs, 4026, Durban, Kwa-Zulu Natal, South Africa
| | - Kehinde Adebola
- Department of Public Health, Babcock University, Ilisan Remo, Ogun State, Nigeria
| | - Roger Coopoosamy
- Department of Nature Conservation, Faculty of Natural Sciences, Mangosuthu University of Technology, P.O. Box 12363, Jacobs, 4026, Durban, Kwa-Zulu Natal, South Africa
| | - Anthony Afolayan
- Medicinal Plants and Economic Development (MPED) Research Centre, Botany Department, University of Fort Hare, Alice Campus, South Africa
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Aljohani S, Layqah L, Masuadi E, Al Alwan B, Baharoon W, Gramish J, Baharoon S. Occurrence of vancomycin MIC creep in methicillin resistant isolates in Saudi Arabia. J Infect Public Health 2020; 13:1576-1579. [PMID: 32859551 DOI: 10.1016/j.jiph.2020.07.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/16/2020] [Accepted: 07/13/2020] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND "MIC creep" is a phenomenon that describes an increase of an organism MICs over time and have been reported from different parts of the world. High MIC in MRSA has been theoretically liked to treatment failure and may be a precursor to hVISA and VISA. This study was conducted to assess presence of vancomycin minimum inhibitory concentration (MIC) creeps among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in Saudi Arabia. METHODS Minimum inhibitory concentration (MIC) of vancomycin by E test of all MRSA isolates of from 2013 to 2018 were reviewed. RESULTS Of the 736 isolates evaluated, no isolates with MIC above 2 were found. Majority of MRSA isolates were susceptible to vancomycin with MIC less than 1. There was a significant increase in both Arithmetic and geometric mean MIC for vancomycin during the first three years which progressively declined in the next three years. CONCLUSIONS Although most of MRSA isolated remained very susceptible to vancomycin there was evidence of dynamic vancomycin MIC creep over time.
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Affiliation(s)
- Sameerah Aljohani
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Laila Layqah
- Department of Research Office, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
| | - Emad Masuadi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Bassam Al Alwan
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Waleed Baharoon
- College of Dentistry, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | | | - Salim Baharoon
- Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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Padrão T, Coelho CC, Costa P, Alegrete N, Monteiro FJ, Sousa SR. Combining local antibiotic delivery with heparinized nanohydroxyapatite/collagen bone substitute: A novel strategy for osteomyelitis treatment. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 119:111329. [PMID: 33321574 DOI: 10.1016/j.msec.2020.111329] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 06/06/2020] [Accepted: 07/21/2020] [Indexed: 01/09/2023]
Abstract
Osteomyelitis is a major challenge in bone surgery and conventional treatment is frequently ineffective to control the infection, with an alternative approach being required. In the present work, a heparinized nanohydroxyapatite/collagen biocomposite was produced in granular form, and loaded with vancomycin, to work as a local drug delivery system for osteomyelitis and as a bone substitute. This strategy involves the local delivery of high concentrations of vancomycin, to eradicate the infection. Additionally, these granules work as a scaffold with regenerative properties, to induce bone regeneration after antibiotic release. The heparinized nanohydroxyapatite/collagen granular bone substitute was produced using two different sintering temperatures to study their effect on granules properties and on vancomycin release profile. Morphological, topographic, chemical and mechanical characterization were carried out for granules sintered at both temperatures and some relevant differences were found. The mechanical strength was increased by several orders of magnitude with increasing sintering temperature, being able to maintain their porous macrostructure and withstand important processes for their commercialization such as packaging, shipping and surgical manipulation. The nanohydroxyapatite/collagen granules were able to release high concentrations of vancomycin, always above MIC, for 19 days. The released antibiotic was able to eradicate both planktonic and sessile methicillin-resistant Staphylococcus aureus. The cytotoxicity was assessed according to ISO 10993-5:2009 and the granules sintered at higher temperature showed no cytotoxic effect. Considering these results nanohydroxyapatite/collagen biocomposite loaded with vancomycin is a promising solution for osteomyelitis treatment.
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Affiliation(s)
- Tatiana Padrão
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; FEUP- Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-135 Porto, Portugal.
| | - Catarina C Coelho
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; FEUP- Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-135 Porto, Portugal; FLUIDINOVA, S.A., Maia, Portugal, Rua Engenheiro Frederico Ulrich, 2650, 4470-605 Moreira da Maia, Portugal
| | - Paulo Costa
- UCIBIO, REQUIMTE, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Nuno Alegrete
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; FMUP- Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Fernando J Monteiro
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; FEUP- Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-135 Porto, Portugal
| | - Susana R Sousa
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ISEP - Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 431, 4200-072 Porto, Portugal
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Dolan E, Hellinga R, London M, Ryan K, Dehority W. Effect of Vancomycin Loading Doses on the Attainment of Target Trough Concentrations in Hospitalized Children. J Pediatr Pharmacol Ther 2020; 25:423-430. [PMID: 32641912 DOI: 10.5863/1551-6776-25.5.423] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Subtherapeutic vancomycin trough concentrations are common in children and may be associated with suboptimal therapeutic response. Our objective was to determine if vancomycin loading doses safely increase the frequency of target trough attainment in hospitalized children. METHODS Patients (≥6 months and <18-years-old) who received a vancomycin loading dose between February 1, 2018, and January 30, 2019, were retrospectively enrolled. These patients were compared to a convenience cohort of patients hospitalized between January 1, 2015, and December 31, 2015, who received vancomycin without a loading dose. Target trough concentrations were defined as >15 mg/dL for invasive infections and >10 mg/dL for non-invasive infections. RESULTS A total of 151 patients were enrolled, with 77 in the control arm and 74 in the loading dose arm. There was no significant difference in the frequency of comorbidities or need for intensive care unit admission between the two arms. Those receiving a vancomycin loading dose were older (mean age 9.1 vs 5.2 years, p < 0.0001). Patients given a loading dose achieved higher mean initial trough values (13.0 mg/dL vs 9.2 mg/dL, p < 0.0001), were more likely to have an initial trough at or above target (37.0% vs 10.4%, p = 0.0001), were more likely to reach target trough values at any point during therapy (52.1% vs 32.9%, p = 0.0081), and attained a target trough concentration more quickly (mean 41.1 hours vs 58.8 hours, p = 0.0118). There were no significant differences in the frequency of serum creatinine elevation or oliguria at the end of therapy. CONCLUSIONS Vancomycin loading doses may improve the ability to safely obtain target trough values in hospitalized children.
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