|
1
|
Puttawong J, Yingkajorn M, Khongkow P, Thamphiwatana SD, Phairatana T. Anti-Methicillin-Resistant Staphylococcus aureus Efficacy of Layer-by-Layer Silver Nanoparticle/Polyacrylic Acid-Coated Titanium Using an In-House Dip Coater. Polymers (Basel) 2025; 17:333. [PMID: 39940535 PMCID: PMC11820344 DOI: 10.3390/polym17030333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/17/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) is still posing a global challenge in healthcare settings. This bacterial strain is a cause of severe periprosthetic infection, thereby impairing the success of implant insertion. To address this issue, implant surface modification is required. Herein, we developed a novel multilayered silver nanoparticle/polyacrylic acid-coated Ti plate (AgNPs/PAA/Ti) using an in-house dip coater. AgNPs were synthesized and characterized. The dip-coating process was optimized based on the dipping rate, evaporation time, and coating cycle number. Uniform and reproducible coatings were achieved on Ti surfaces, with consistency verified through SEM analysis. The average size of the AgNPs was approximately 36.50 ± 0.80 nm with a PDI of 0.443 ± 0.025, and the zeta potential was measured at around -23.3 ± 2.0 mV. The maximum coating thickness of 83.5 ± 1.3 µm was observed at 15 cycles of dip coating. Moreover, our developed AgNPs/PAA/Ti plate showed both antimicrobial and biofilm-resistant performance, while also exhibiting enhanced biocompatibility with cultured MG63 osteosarcoma cells, maintaining cell viability greater than 70%. We envisage that this material holds significant promise as a candidate for medical implant devices, offering protection against MRSA-associated infection at insertion sites with low vascularity in the future.
Collapse
Affiliation(s)
- Julinthip Puttawong
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (J.P.); (P.K.)
| | - Mingkwan Yingkajorn
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand;
| | - Pasarat Khongkow
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (J.P.); (P.K.)
- Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
| | - Soracha D. Thamphiwatana
- Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakornpathom 73170, Thailand
- International School of Engineering (ISE), Faculty of Engineering, Chulalongkorn University, Bangkok 10330, Thailand
| | - Tonghathai Phairatana
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (J.P.); (P.K.)
- Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
| |
Collapse
|
|
2
|
Yamazaki Y, Ito T, Tamai M, Nakagawa S, Nakamura Y. The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections. Inflamm Regen 2024; 44:9. [PMID: 38429810 PMCID: PMC10905890 DOI: 10.1186/s41232-024-00323-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/15/2024] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND Staphylococcus aureus is a leading cause of human bacterial infections worldwide. It is the most common causative agent of skin and soft tissue infections, and can also cause various other infections, including pneumonia, osteomyelitis, as well as life-threatening infections, such as sepsis and infective endocarditis. The pathogen can also asymptomatically colonize human skin, nasal cavity, and the intestine. S. aureus colonizes approximately 20-30% of human nostrils, being an opportunistic pathogen for subsequent infection. Its strong ability to silently spread via human contact makes it difficult to eradicate S. aureus. A major concern with S. aureus is its capacity to develop antibiotic resistance and adapt to diverse environmental conditions. The variability in the accessory gene regulator (Agr) region of the genome contributes to a spectrum of phenotypes within the bacterial population, enhancing the likelihood of survival in different environments. Agr functions as a central quorum sensing (QS) system in S. aureus, allowing bacteria to adjust gene expression in response to population density. Depending on Agr expression, S. aureus secretes various toxins, contributing to virulence in infectious diseases. Paradoxically, expressing Agr may be disadvantageous in certain situations, such as in hospitals, causing S. aureus to generate Agr mutants responsible for infections in healthcare settings. MAIN BODY This review aims to demonstrate the molecular mechanisms governing the diverse phenotypes of S. aureus, ranging from a harmless colonizer to an organism capable of infecting various human organs. Emphasis will be placed on QS and its role in orchestrating S. aureus behavior across different contexts. SHORT CONCLUSION The pathophysiology of S. aureus infection is substantially influenced by phenotypic changes resulting from factors beyond Agr. Future studies are expected to give the comprehensive understanding of S. aureus overall profile in various settings.
Collapse
Affiliation(s)
- Yuriko Yamazaki
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka, University, Osaka, 565-0871, Japan
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Tomoka Ito
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Masakazu Tamai
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Seitaro Nakagawa
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Yuumi Nakamura
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka, University, Osaka, 565-0871, Japan.
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
| |
Collapse
|
|
3
|
Gulone L, Di Gregorio S, Morales M, Haim MS, García S, Perazzi B, Famiglietti A, Mollerach M. The Changing Epidemiology and Antimicrobial Susceptibility of Staphylococcus aureus Isolated from Blood Cultures in a University Hospital from Argentina. Microb Drug Resist 2024; 30:109-117. [PMID: 38133499 DOI: 10.1089/mdr.2023.0219] [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] [Indexed: 12/23/2023] Open
Abstract
Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections worldwide. In this study, we demonstrated changes in SAB epidemiology in an Argentinean University Hospital during an 8-year period (2009-2016). A total of 326 S. aureus clinical isolates were recovered in three periods: P1: 2009-2010, P2: 2012-2014, and P3: 2015-2016. Among these, 127 were methicillin-resistant S. aureus (MRSA) and were characterized by phenotypic and molecular methods. We hereby report a significant decline in multiple drug resistance among MRSA isolates associated with an increase in SCCmec IV between the three periods. A diversity of MRSA-IV clones (mainly ST30-MRSA-IV, ST5-MRSA-IV, and ST8-MRSA-IV) replaced between 2009 and 2016 the previous prevalent MRSA clone causing bloodstream infections at this hospital (ST5-MRSA-I). MRSA population structure continued to diversify between P2 and P3. Notably, ST8-MRSA-IV-t008 related to USA300 was first detected during P2, and ST8-MRSA-IV together with ST30-MRSA-IV related to the Southwest Pacific clone were the more prevalent MRSA genotypes circulating during P3.
Collapse
Affiliation(s)
- Lucía Gulone
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Ciudad Autónoma de Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| | - Sabrina Di Gregorio
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Ciudad Autónoma de Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| | - Maia Morales
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Laboratorio de Bacteriología Clínica, Ciudad Autónoma de Buenos Aires, Argentina
| | - María Sol Haim
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Ciudad Autónoma de Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| | - Susana García
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Laboratorio de Bacteriología Clínica, Ciudad Autónoma de Buenos Aires, Argentina
| | - Beatriz Perazzi
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Laboratorio de Bacteriología Clínica, Ciudad Autónoma de Buenos Aires, Argentina
| | - Angela Famiglietti
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Laboratorio de Bacteriología Clínica, Ciudad Autónoma de Buenos Aires, Argentina
| | - Marta Mollerach
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Ciudad Autónoma de Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| |
Collapse
|
|
4
|
Nolan J, McCarthy K, Farkas A, Avent ML. Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study. Int J Clin Pharm 2023; 45:1444-1451. [PMID: 37532840 DOI: 10.1007/s11096-023-01618-5] [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: 01/26/2023] [Accepted: 06/24/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25 mg/L. AIM To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. METHOD A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. RESULTS Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613 mg.h/L with CSS 25 mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250 mg/24 h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. CONCLUSION Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.
Collapse
Affiliation(s)
- J Nolan
- The Royal Brisbane and Women's Hospital, Herston, Australia.
- School of Medicine, University of Queensland, 4029, Herston, Australia.
| | - K McCarthy
- The Royal Brisbane and Women's Hospital, Herston, Australia
- School of Medicine, University of Queensland, 4029, Herston, Australia
| | - A Farkas
- Mount Sinai West Hospital, New York, USA
- Optimum Dosing Strategies, Bloomingdale, New York, USA
| | - M L Avent
- The Royal Brisbane and Women's Hospital, Herston, Australia
- Queensland Statewide Antimicrobial Stewardship Program, University of Queensland Centre for Clinical Research, Herston, Australia
| |
Collapse
|
|
5
|
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.
Collapse
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.
| |
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Kitaya S, Kanamori H, Katori Y, Tokuda K. Clinical Characteristics and Outcomes of Persistent Staphylococcal Bacteremia in a Tertiary Care Hospital. Antibiotics (Basel) 2023; 12:antibiotics12030454. [PMID: 36978326 PMCID: PMC10044455 DOI: 10.3390/antibiotics12030454] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/15/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
Clinical outcomes of persistent staphylococcal bacteremia vary depending on the causative organism. This secondary data analysis study compared the clinical characteristics of persistent Staphylococcus aureus (S. aureus)- and coagulase-negative staphylococci (CoNS)-caused bacteremia, focusing on the methicillin-resistant status. This study used data collected from patients who underwent blood cultures between January 2012 and December 2021 at Tohoku University Hospital, Japan. Patients with persistent staphylococcal bacteremia were divided into groups based on the pathogen and methicillin-resistant status, and their characteristics were analyzed. The primary outcomes were early (30-day), late (30–90 days), and 90-day mortality rates. The early, late, and 90-day mortality rates were similar between the persistent CoNS and S. aureus bacteremia groups. Patients with persistent methicillin-resistant S. aureus (MRSA) bacteremia tended to have higher early, late, and 90-day mortality rates than those with persistent methicillin-susceptible S. aureus bacteremia (not statistically significant). No differences were observed between the methicillin-resistant and-susceptible CoNS groups. In patients with persistent CoNS bacteremia, mortality tended to increase, especially in debilitated or immunocompromised patients with distant metastases, underscoring the importance of infection source control. Mortality tended to be high in patients with persistent MRSA bacteremia, especially when persistent bacteremia clearance was not confirmed, illustrating the need for careful therapeutic management.
Collapse
Affiliation(s)
- Shiori Kitaya
- Department of Infectious Diseases, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
- Department of Otolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
- Correspondence: (S.K.); (H.K.); Tel.: +81-22-717-7373 (S.K.)
| | - Hajime Kanamori
- Department of Infectious Diseases, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
- Correspondence: (S.K.); (H.K.); Tel.: +81-22-717-7373 (S.K.)
| | - Yukio Katori
- Department of Otolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
| | - Koichi Tokuda
- Department of Infectious Diseases, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
| |
Collapse
|
|
8
|
Parsons JB, Westgeest AC, Conlon BP, Fowler VG. Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Host, Pathogen, and Treatment. Antibiotics (Basel) 2023; 12:455. [PMID: 36978320 PMCID: PMC10044482 DOI: 10.3390/antibiotics12030455] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 03/02/2023] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating pathogen responsible for a variety of life-threatening infections. A distinctive characteristic of this pathogen is its ability to persist in the bloodstream for several days despite seemingly appropriate antibiotics. Persistent MRSA bacteremia is common and is associated with poor clinical outcomes. The etiology of persistent MRSA bacteremia is a result of the complex interplay between the host, the pathogen, and the antibiotic used to treat the infection. In this review, we explore the factors related to each component of the host-pathogen interaction and discuss the clinical relevance of each element. Next, we discuss the treatment options and diagnostic approaches for the management of persistent MRSA bacteremia.
Collapse
Affiliation(s)
- Joshua B. Parsons
- Department of Medicine, Division of Infectious Disease, Duke University Medical Center, Durham, NC 27710, USA
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Annette C. Westgeest
- Department of Medicine, Division of Infectious Disease, Duke University Medical Center, Durham, NC 27710, USA
- Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Brian P. Conlon
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Vance G. Fowler
- Department of Medicine, Division of Infectious Disease, Duke University Medical Center, Durham, NC 27710, USA
- Duke Clinical Research Institute, Durham, NC 27710, USA
| |
Collapse
|
|
9
|
Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. Pharmaceutics 2022; 14:pharmaceutics14030489. [PMID: 35335866 PMCID: PMC8955715 DOI: 10.3390/pharmaceutics14030489] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 01/08/2023] Open
Abstract
Background: To promote model-informed precision dosing (MIPD) for vancomycin (VCM), we developed statements for therapeutic drug monitoring (TDM). Methods: Ten clinical questions were selected. The committee conducted a systematic review and meta-analysis as well as clinical studies to establish recommendations for area under the concentration-time curve (AUC)-guided dosing. Results: AUC-guided dosing tended to more strongly decrease the risk of acute kidney injury (AKI) than trough-guided dosing, and a lower risk of treatment failure was demonstrated for higher AUC/minimum inhibitory concentration (MIC) ratios (cut-off of 400). Higher AUCs (cut-off of 600 μg·h/mL) significantly increased the risk of AKI. Although Bayesian estimation with two-point measurement was recommended, the trough concentration alone may be used in patients with mild infections in whom VCM was administered with q12h. To increase the concentration on days 1–2, the routine use of a loading dose is required. TDM on day 2 before steady state is reached should be considered to optimize the dose in patients with serious infections and a high risk of AKI. Conclusions: These VCM TDM guidelines provide recommendations based on MIPD to increase treatment response while preventing adverse effects.
Collapse
|
|
10
|
Point-Counterpoint: Should Clinical Microbiology Laboratories Report Vancomycin MICs? J Clin Microbiol 2021; 59:JCM.00239-21. [PMID: 33536296 DOI: 10.1128/jcm.00239-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTIONWith numerous reported challenges to reporting MICs for vancomycin, clinical laboratories are attempting to identify accurate methods for MIC testing. However, the issues of poor reproducibility, accuracy, and clinical utility remain a challenge. In this Point-Counterpoint, Dr. Sara Revolinski discusses the pros of reporting MICs for vancomycin, while Dr. Christopher Doern argues for the use of caution.
Collapse
|
|
11
|
Lee SO, Lee S, Lee JE, Song KH, Kang CK, Wi YM, San-Juan R, López-Cortés LE, Lacoma A, Prat C, Jang HC, Kim ES, Kim HB, Lee SH. Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis. Sci Rep 2020; 10:20697. [PMID: 33244173 PMCID: PMC7691521 DOI: 10.1038/s41598-020-77729-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022] Open
Abstract
The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.
Collapse
Affiliation(s)
- Soon Ok Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea
| | - Shinwon Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea.
| | - Jeong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea
| | - Kyoung-Ho Song
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Chang Kyung Kang
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea
| | - Yu Mi Wi
- Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Rafael San-Juan
- Unit of Infectious Diseases, University Hospital 12 de Octubre, Instituto de Investigación Hospital "12 de Octubre" (i+12), Universidad Complutense, Avenida de Córdoba, s/n, Madrid, Spain
| | - Luis E López-Cortés
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla, Sevilla, Spain
| | - Alicia Lacoma
- Microbiology Department, Hospital Universitari Germans Trias i Pujol, Institut d' Investigació Germans Trias i Pujol, CIBER Enfermedades Respiratorias (CIBERES), Universitat Autònoma de Barcelona, Badalona, Spain
| | - Cristina Prat
- Microbiology Department, Hospital Universitari Germans Trias i Pujol, Institut d' Investigació Germans Trias i Pujol, CIBER Enfermedades Respiratorias (CIBERES), Universitat Autònoma de Barcelona, Badalona, Spain.,Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hee-Chang Jang
- Department of Infectious Diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea
| | - Eu Suk Kim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hong Bin Kim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sun Hee Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea
| |
Collapse
|
|
12
|
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: 120] [Impact Index Per Article: 24.0] [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.
Collapse
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.
| |
Collapse
|
|
13
|
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.
Collapse
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
| |
Collapse
|
|
14
|
Luzum M, Sebolt J, Chopra V. Catheter-Associated Urinary Tract Infection, Clostridioides difficile Colitis, Central Line-Associated Bloodstream Infection, and Methicillin-Resistant Staphylococcus aureus. Med Clin North Am 2020; 104:663-679. [PMID: 32505259 DOI: 10.1016/j.mcna.2020.02.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hospital-acquired infections increase cost, morbidity, and mortality for patients across the United States and the world. Principal among these infections are central line-associated bloodstream infection, catheter-associated urinary tract infection, Clostridioides difficile, and methicillin-resistant Staphylococcus aureus colonization and infections. This article provides succinct summaries of the background, epidemiology, diagnosis, and treatment of these conditions. In addition, novel prevention strategies, including those related to recent national interventions, are reviewed.
Collapse
Affiliation(s)
- Matthew Luzum
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA
| | - Jonathan Sebolt
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA
| | - Vineet Chopra
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA.
| |
Collapse
|
|
15
|
Kuehl R, Morata L, Meylan S, Mensa J, Soriano A. When antibiotics fail: a clinical and microbiological perspective on antibiotic tolerance and persistence of Staphylococcus aureus. J Antimicrob Chemother 2020; 75:1071-1086. [PMID: 32016348 DOI: 10.1093/jac/dkz559] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Staphylococcus aureus is a major human pathogen causing a vast array of infections with significant mortality. Its versatile physiology enables it to adapt to various environments. Specific physiological changes are thought to underlie the frequent failure of antimicrobial therapy despite susceptibility in standard microbiological assays. Bacteria capable of surviving high antibiotic concentrations despite having a genetically susceptible background are described as 'antibiotic tolerant'. In this review, we put current knowledge on environmental triggers and molecular mechanisms of increased antibiotic survival of S. aureus into its clinical context. We discuss animal and clinical evidence of its significance and outline strategies to overcome infections with antibiotic-tolerant S. aureus.
Collapse
Affiliation(s)
- Richard Kuehl
- Service of Infectious Diseases, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Laura Morata
- Service of Infectious Diseases, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Sylvain Meylan
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
- Division de Maladies Infectieuses, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Josep Mensa
- Service of Infectious Diseases, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Alex Soriano
- Service of Infectious Diseases, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| |
Collapse
|
|
16
|
Jensen J, Packert D, Miller C, Packert G, Hanft J, Jensen S. Discovery and Development of Gaseous Nitric Oxide Under Increased Atmospheric Pressure as an Antimicrobial: In Vitro and In Vivo Testing of Nitric Oxide Against Multidrug-Resistant Organisms. Clin Podiatr Med Surg 2020; 37:231-246. [PMID: 32146980 DOI: 10.1016/j.cpm.2019.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Gaseous nitric oxide under increased atmospheric pressure (gNOp) has shown ability to kill multidrug-resistant bacteria in an in vitro model and in a live mammalian (porcine) model. Factors impacting the kill rate of the multidrug-resistant bacteria include atmospheric pressures, concentration of gaseous NO, flow rate, and duration of application. Using successful in vitro parameters, gNOp showed multilog reduction of bacteria in a live mammalian (porcine) model. The in vitro testing system, using the EpiDerm-FT skin model (stem cell grown skin), was used to develop an infected wound model for Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S aureus.
Collapse
Affiliation(s)
- Jeffrey Jensen
- Midwestern University, Arizona School of Podiatric Medicine, 19555 North 59th Avenue, Glendale, AZ 85308, USA; Hansen Pharmaceutical, LLC, 7000 SW 62nd Avenue, Suite 405, South Miami, FL 33143, USA.
| | - Daniel Packert
- College of Nursing and Health Sciences, Barry University, Sienna Building, Room 221, 11300 Northeast 2nd Avenue, Miami Shores, FL 33161, USA
| | - Chris Miller
- Hansen Pharmaceutical, LLC, 7000 SW 62nd Avenue, Suite 405, South Miami, FL 33143, USA; Faculty of Medicine, Respiratory Division, The University of British Columbia, Room 258, 2260 Oak Street, Vancouver, British Columbia v5Z 1M9, Canada
| | - Gerhild Packert
- Clinical Biology Department, Barry University, 11300 NE 2nd Avenue, Miami Shores, FL 33161, USA
| | - Jason Hanft
- Hansen Pharmaceutical, LLC, 7000 SW 62nd Avenue, Suite 405, South Miami, FL 33143, USA; Foot & Ankle Institute of South Florida, 7000 Southwest 62nd Avenue, Suite 405, South Miami, FL 33143, USA; Doctors Research Network, South Miami, FL, USA
| | - Steven Jensen
- Hansen Pharmaceutical, LLC, 7000 SW 62nd Avenue, Suite 405, South Miami, FL 33143, USA
| |
Collapse
|
|
17
|
Kresken M, Grabein B, Becker K, Straube E, Wichelhaus TA, Willinger B. Calculated parenteral initial treatment of bacterial infections: Microbiology. GMS INFECTIOUS DISEASES 2020; 8:Doc18. [PMID: 32373443 PMCID: PMC7186810 DOI: 10.3205/id000062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This is the second chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Preliminary microbiological findings regarding the patient and their immediate environment are crucial for the calculation of treatment with antibiotics in each case, as well as the resistance situation of the ward on which the patient is being cared for. If such data is not available, regional or supra-regional data can be used as a fallback. This chapter describes the methods of susceptibility testing, informs about the resistance situation in Germany and describes the main resistance mechanisms of bacterial pathogens against antibiotics. Further, the chapter informs about collateral damage of antibiotics as well as medical measures against increasing resistance.
Collapse
Affiliation(s)
- Michael Kresken
- Antiinfectives Intelligence GmbH, Campus Hochschule Bonn-Rhein-Sieg, Rheinbach, Germany
- Rheinische Fachhochschule Köln gGmbH, Cologne, Germany
| | - Béatrice Grabein
- Stabsstelle Klinische Mikrobiologie und Krankenhaushygiene, Klinikum der Universität München, Munich, Germany
| | - Karsten Becker
- Institut für Medizinische Mikrobiologie, Universitätsklinikum Münster, Germany
| | - Eberhard Straube
- Institut für Medizinische Mikrobiologie, Universitätsklinikum Jena, Germany
| | - Thomas A. Wichelhaus
- Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universitätsklinikum Frankfurt, Germany
| | - Birgit Willinger
- Klinisches Institut für Labormedizin, Medizinische Universität Wien, Vienna, Austria
| |
Collapse
|
|
18
|
Al-Sulaiti FK, Nader AM, Saad MO, Shaukat A, Parakadavathu R, Elzubair A, Al-Badriyeh D, Elewa H, Awaisu A. Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial. Eur J Drug Metab Pharmacokinet 2019; 44:639-652. [PMID: 30919233 PMCID: PMC6746691 DOI: 10.1007/s13318-019-00551-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration-time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. OBJECTIVES We aimed to compare clinical and pharmacokinetic outcomes between peak-trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. METHODS A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak-trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. RESULTS Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak-trough-based-TDM (n = 30)]. Peak-trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak-trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak-trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak-trough-based group. CONCLUSION Maintenance of target vancomycin exposures and implementation of peak-trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.
Collapse
Affiliation(s)
- Fatima Khalifa Al-Sulaiti
- Clinical Pharmacy and Practice Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar
- Qatar National Research Fund, Qatar Foundation, Doha, Qatar
| | | | - Mohamed Omar Saad
- Clinical Pharmacy Department, Al-Wakrah Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Adila Shaukat
- Infectious Diseases Department, Al-Wakrah Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Rakesh Parakadavathu
- Infectious Diseases Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Ahmed Elzubair
- Clinical Pharmacy Department, Al-Khor Hospital, Hamad Medical Corporation, Al-Khor, Qatar
| | - Daoud Al-Badriyeh
- Clinical Pharmacy and Practice Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Hazem Elewa
- Clinical Pharmacy and Practice Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Ahmed Awaisu
- Clinical Pharmacy and Practice Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
| |
Collapse
|
|
19
|
Sáez C, Sarriá C, Vilacosta I, Olmos C, López J, García-Granja PE, Fernández C, de las Cuevas C, Reyes G, Domínguez L, San Román JA. "A contemporary description of staphylococcus aureus prosthetic valve endocarditis. Differences according to the time elapsed from surgery". Medicine (Baltimore) 2019; 98:e16903. [PMID: 31464922 PMCID: PMC6736462 DOI: 10.1097/md.0000000000016903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 07/08/2019] [Accepted: 07/26/2019] [Indexed: 11/26/2022] Open
Abstract
Staphylococcus aureus prosthetic valve endocarditis (SAPVE) has a poor prognosis. There are no large series that accurately describe this entity.This is a retrospective observational study on a prospective cohort from 3 Spanish reference hospitals for cardiac surgery, including 78 definitive episodes of left SAPVE between 1996 and 2016.Fifty percent had a Charlson Index score >5; 53% were health care-related. Twenty percent did not present fever. Complications at diagnosis included: severe heart failure (HF, 29%), septic shock (SS, 17.9%), central nervous system abnormalities (19%), septic metastasis (4%). Hemorrhagic stroke was not higher in anticoagulated patients. Twenty-seven percent were methicilin-resistant SA (MRSA). Fifteen of 31 had positive valve culture; it was related to surgery within first 24 hours. At diagnosis, 69% had vegetation (>10 mm in 75%), 21.8% perianular extension, and 20% prosthetic dehiscence. Forty-eight percent had persistent bacteremia, related to nonsurgical treatment. Perianular extension progressed in 18%. Surgery was performed in 35 episodes (12 with stroke). Eleven uncomplicated episodes were managed with medical therapy, 8 survived. In-hospital mortality was 55%, higher in episodes with hemorrhagic stroke (77.8% vs 52.2%, odds ratio 3.2 [0.62-16.55]). Early SAPVE was nosocomial (92%), presented as severe HF (54%), patients were diagnosed and operated on early, 38% died. In intermediate SAPVE (9 weeks-1 year) diagnosis was delayed (24%), patients presented with constitutional syndrome (18%), renal failure (41%), and underwent surgery >72 hours after indication; 53% died. Late SAPVE (>1 year) was related with health care, diagnosis delay, and 60% of deceases.Left SAPVE frequently affected patients with comorbidity and health care contact. Complications at diagnosis and absence of fever were frequent. Presence of MRSA was high. Positive valve culture was related to early surgery. Paravalvular extension was frequent; vegetations were large, but its absence at diagnosis was common. Some uncomplicated SAPVE episodes were safety treated with medical therapy. Surgery was feasible in patients with stroke. Mortality was high. There were differences in some clinical characteristics and in evolution according to the time elapsed from valve replacement. Prognosis was better in early SAPVE.
Collapse
Affiliation(s)
- Carmen Sáez
- Department of Medicine-Infectious diseases, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain
| | - Cristina Sarriá
- Department of Medicine-Infectious diseases, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain
| | - Isidre Vilacosta
- Instituto Cardiovascular. Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Carmen Olmos
- Instituto Cardiovascular. Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Javier López
- Department of Cardiology, Instituto de Ciencias del Corazón (ICICOR), CIBERCV, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Pablo Elpidio García-Granja
- Department of Cardiology, Instituto de Ciencias del Corazón (ICICOR), CIBERCV, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Cristina Fernández
- Instituto Cardiovascular. Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Carmen de las Cuevas
- Department of Microbiology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria, Universidad Autónoma de Madrid, Spain
| | - Guillermo Reyes
- Department of Cardiac Surgery, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria, Universidad Autónoma de Madrid, Spain
| | - Lourdes Domínguez
- Department of Cardiology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria, Universidad Autónoma de Madrid, Spain
| | - Jose Alberto San Román
- Department of Cardiology, Instituto de Ciencias del Corazón (ICICOR), CIBERCV, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| |
Collapse
|
|
20
|
Dorajoo SR, Winata CL, Goh JHF, Ooi ST, Somani J, Yeoh LY, Lee SY, Yap CW, Chan A, Chae JW. Optimizing Vancomycin Dosing in Chronic Kidney Disease by Deriving and Implementing a Web-Based Tool Using a Population Pharmacokinetics Analysis. Front Pharmacol 2019; 10:641. [PMID: 31244657 PMCID: PMC6581063 DOI: 10.3389/fphar.2019.00641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/17/2019] [Indexed: 11/28/2022] Open
Abstract
Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes.
Collapse
Affiliation(s)
- Sreemanee Raaj Dorajoo
- Department of Pharmacy, National University of Singapore, Singapore, Singapore.,Department of Pharmacy, Khoo Teck Puat Hospital, Singapore, Singapore
| | | | - Jessica Hui Fen Goh
- Department of Pharmacy, National University of Singapore, Singapore, Singapore.,Department of Pharmacy, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Say Tat Ooi
- Department of Medicine (Infectious Diseases), Khoo Teck Puat Hospital, Singapore, Singapore
| | - Jyoti Somani
- Department of Medicine (Infectious Diseases), Khoo Teck Puat Hospital, Singapore, Singapore
| | - Lee Ying Yeoh
- Department of Medicine (Renal Medicine), Khoo Teck Puat Hospital, Singapore, Singapore
| | - Siok Ying Lee
- Department of Pharmacy, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Chun Wei Yap
- Health Services & Outcomes Research, National Healthcare Group, Singapore, Singapore
| | - Alexandre Chan
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Jung-Woo Chae
- Department of Pharmacy, National University of Singapore, Singapore, Singapore.,College of Pharmacy, Chungnam National University, Daejeon, South Korea
| |
Collapse
|
|
21
|
Diagnosis and treatment of catheter-related bloodstream infection: Clinical guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology and (SEIMC) and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC). Med Intensiva 2019; 42:5-36. [PMID: 29406956 DOI: 10.1016/j.medin.2017.09.012] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 09/29/2017] [Accepted: 09/29/2017] [Indexed: 12/14/2022]
Abstract
Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and [SEIMC] and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units [SEMICYUC]). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications.
Collapse
|
|
22
|
Sipahi OR, Kahraman H, Erdem HA, Yetkin F, Kaya S, Demirdal T, Tunccan OG, Karasahin O, Oruc E, Cag Y, Kurtaran B, Ulug M, Kutlu M, Avci M, Oztoprak N, Arda B, Pullukcu H, Tasbakan M, Yamazhan T, Kandemir O, Dizbay M, Sipahi H, Ulusoy S. Daptomycin vs. glycopeptides in the treatment of febrile neutropenia: results of the Izmir matched cohort study. Infection 2018; 47:259-266. [PMID: 30498901 DOI: 10.1007/s15010-018-1256-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 11/21/2018] [Indexed: 10/27/2022]
Abstract
PURPOSE In this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin). METHODS Data and outcomes of adult (aged > 18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status. RESULTS Overall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72 h antibiotic treatment (p = 0.25). There was no significant difference in cured, improved and (cured + improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p > 0.05). There was also no significant difference (p > 0.05), in terms of persistent response in the (D) versus (G) cohorts, CONCLUSIONS: These findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.
Collapse
Affiliation(s)
- Oguz Resat Sipahi
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Hasip Kahraman
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey.
| | - Huseyin Aytac Erdem
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Funda Yetkin
- Department of Infectious Diseases and Clinical Microbiology, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Selcuk Kaya
- Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Tuna Demirdal
- Department of Infectious Diseases and Clinical Microbiology, Katip Celebi University Faculty of Medicine, Izmir, Turkey
| | - Ozlem Guzel Tunccan
- Department of Infectious Diseases and Clinical Microbiology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Omer Karasahin
- Department of Infectious Diseases and Clinical Microbiology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Ebru Oruc
- Department of Infectious Diseases and Clinical Microbiology, Baskent University Faculty of Medicine, Adana, Turkey
| | - Yasemin Cag
- Department of Infectious Diseases and Clinical Microbiology, Dr. Lütfi Kirdar Training and Research Hospital, Istanbul, Turkey
| | - Behice Kurtaran
- Department of Infectious Diseases and Clinical Microbiology, Cukurova University Faculty of Medicine, Adana, Turkey
| | - Mehmet Ulug
- Infectious Diseases Clinic, Eskisehir Private Umit Hospital, Eskisehir, Turkey
| | - Murat Kutlu
- Department of Infectious Diseases and Clinical Microbiology, Pamukkale University Faculty of Medicine, Denizli, Turkey
| | - Meltem Avci
- Infectious Disease and Clinical Microbiology Clinic, İzmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | - Nefise Oztoprak
- Department of Infectious Diseases and Clinical Microbiology Clinic, Antalya Training and Research Hospital, Antalya, Turkey
| | - Bilgin Arda
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Husnu Pullukcu
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Meltem Tasbakan
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Tansu Yamazhan
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Ozlem Kandemir
- Department of Clinical Microbiology and Infectious Diseases, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Murat Dizbay
- Department of Infectious Diseases and Clinical Microbiology, Gazi University Faculty of Medicine, Ankara, Turkey
| | | | - Sercan Ulusoy
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey
| |
Collapse
|
|
23
|
Tsai CY, Lee CH, Chien CC, Chen IL. Impact of teicoplanin maintenance dose and MIC values on the clinical outcomes of patients treated for methicillin-resistant Staphylococcus aureus bacteremia. Infect Drug Resist 2018; 11:1205-1217. [PMID: 30147349 PMCID: PMC6101025 DOI: 10.2147/idr.s171236] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Objectives Teicoplanin, a glycopeptide, is regarded as among the drug choices for methicillin-resistant Staphylococcus aureus (MRSA) infections. Few studies have evaluated the relationship between teicoplanin minimal inhibitory concentrations (MICs) and outcomes among patients with serious MRSA infections. Subjects and methods We investigated the relationship between teicoplanin maintenance dose and clinical outcomes, on the completion of teicoplanin therapy, in bacteremia patients with MRSA infection, with different teicoplanin MICs. A total of 146 adult patients with MRSA bacteremia were enrolled at Kaohsiung Chang Gung Memorial Hospital between September 2012 and September 2015. Results A higher number of patients in the high-dose regimen group (6 mg/kg/12 h) had favorable outcomes than those in the standard-dose regimen group (6 mg/kg/24 h) (84.1% vs 41.2%; p<0.01), regardless of the teicoplanin MICs. In the multivariate analysis, a Pittsburgh bacteremia score ≥4 (OR, 0.07, 95% CI, 0.03–0.19) was a risk factor for an unfavorable final clinical response, whereas high-dose teicoplanin maintenance therapy for MRSA bacteremia was significantly associated with a favorable final response (OR, 25.3 [95% CI, 4.43–144.03] for isolates with a teicoplanin MIC ≥1.5 mg/L and OR, 5.6 [95% CI, 1.57–19.91] for isolates with a teicoplanin MIC <1.5 mg/L). Survival at 30 days was significantly better for patients receiving high-dose teicoplanin maintenance treatment, regardless of the teicoplanin MICs of the MRSA isolates. Patients were selected using propensity score matching, based on the independent predictors of a favorable final outcome. After appropriate propensity score matching, patients in the high-dose regimen group still had a statistically significant favorable outcome at the end of treatment (84.1% vs 40.9%; p<0.01). Conclusion The results suggested that high-dose teicoplanin maintenance treatment is associated with more favorable outcomes than standard-dose teicoplanin maintenance treatment, for patients with MRSA bacteremia, regardless of the teicoplanin MIC.
Collapse
Affiliation(s)
- Ching-Yen Tsai
- Division of Infectious Diseases, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan,
| | - Chen-Hsiang Lee
- Division of Infectious Diseases, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, .,Chang Gung University College of Medicine, Kaohsiung, Taiwan,
| | - Chun-Chih Chien
- Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - I-Ling Chen
- Department of Pharmacology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| |
Collapse
|
|
24
|
Abelenda Alonso G, Corbacho Loarte MD, Ramos RN, Jiménez MC, Ruiz-Capillas JJJ. Staphylococcus aureus bacteremia in a secondary level Spanish hospital: clinical implications of high vancomycin MIC. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2018; 31:353-362. [PMID: 30014681 PMCID: PMC6172687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVE One of the most controversial issues in recent years has been the clinical significance of high vancomycin MIC in Staphylococcus aureus bacteremia. The aim of this study was to elucidate the clinical implication that this parameter has in the staphylococcal bacteremia of a second level hospital. METHODS Retrospective descriptive study between January 2014 and September 2016 with 138 records from the blood culture Severo Ochoa University Hospital registry. A total of 98 cases were finally analized. Microbiological analysis of vancomycin MIC was performed using micro dilution technique. RESULTS The mean age was 71.4 ± 12.45 and 63.26% of the patients had a Charlson index ≥6. A 30.61% were carriers of a venous central catheter. The most frequent source was venous central catheter (26.53%). There were 14.24% metastatic events. Global mortality rate at 30 days was 25.51%. The 43.87% of strains had a vancomycin MIC ≥ 2 mg/L. High vancomycin MIC was significantly associated with persistent bacteremia (OR 3.12 [1.13-8.93]), maintaining this statistical significance in methicillin-resistant S. aureus (MRSA) group (p =0.001) but no in methicillin-susceptible S. aureus (MSSA) group (p = 0.13). Persistent bacteremia was also significantly related with permanent catheter carriers (OR 4.18 [1.38-12.61]), peripheric catheter source (OR 5.18 [1.13-8.93]) and metastatic complications (OR 3.82 [1.03- 12.81]). There was no significant association between high vancomycin MIC and mortality. CONCLUSIONS High vancomycin MIC may be useful in daily clinical practice as a marker of poor clearance of S. aureus bacteremia, specially when is due to MRSA strains.
Collapse
Affiliation(s)
| | | | - Ruth Núñez Ramos
- Microbiology Clinical Service, Severo Ochoa University Hospital, Leganés, Spain
| | | | | |
Collapse
|
|
25
|
Cavalcanti IMF, Menezes TGC, Campos LADA, Ferraz MS, Maciel MAV, Caetano MNP, Santos-Magalhães NS. Interaction study between vancomycin and liposomes containing natural compounds against methicillin-resistant Staphylococcus aureus clinical isolates. BRAZ J PHARM SCI 2018. [DOI: 10.1590/s2175-97902018000200203] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
|
|
26
|
Lewis PO, Heil EL, Covert KL, Cluck DB. Treatment strategies for persistent methicillin-resistant Staphylococcus aureus bacteraemia. J Clin Pharm Ther 2018; 43:614-625. [PMID: 30003555 DOI: 10.1111/jcpt.12743] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 06/17/2018] [Accepted: 06/22/2018] [Indexed: 01/08/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a long-standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia. METHODS A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin-resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English-language, peer-reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data. RESULTS AND DISCUSSION Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high-dose daptomycin in combination with an antistaphylococcal β-lactam, ceftaroline, trimethoprim-sulfamethoxazole (TMP-SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP-SMX; linezolid alone or in combination with a carbapenem, or telavancin. WHAT IS NEW AND CONCLUSION Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm.
Collapse
Affiliation(s)
- Paul O Lewis
- Department of Pharmacy, Johnson City Medical Center, Johnson City, Tennessee
| | - Emily L Heil
- Department of Pharmacy Practice and Science, School of Pharmacy, University of Maryland, Baltimore, Maryland
| | - Kelly L Covert
- Department of Pharmacy Practice, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee
| | - David B Cluck
- Department of Pharmacy Practice, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee
| |
Collapse
|
|
27
|
Kalimuddin S, Chan YFZ, Phillips R, Ong SP, Archuleta S, Lye DC, Tan TT, Low JGH. A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study. Trials 2018; 19:305. [PMID: 29859132 PMCID: PMC5984763 DOI: 10.1186/s13063-018-2702-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 05/21/2018] [Indexed: 01/18/2023] Open
Abstract
Background Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations. Methods Patients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60. Results A total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3–5 days in the vancomycin arm and 3–7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection. Conclusion Based on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success. Trial registration ClinicalTrials.gov, NCT01975662. Registered on 5 November 2013.
Collapse
Affiliation(s)
- Shirin Kalimuddin
- Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore.
| | - Yvonne F Z Chan
- Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore
| | - Rachel Phillips
- School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London, SE1 1UL, UK.,NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust and King's College London, Guy's Hospital, London, SE1 9RT, UK
| | - Siew Pei Ong
- Geriatric Education and Research Institute, 2 Yishun Central 2, Singapore, 768024, Singapore
| | - Sophia Archuleta
- Division of Infectious Diseases, National University Health System, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Rd, Singapore, 119077, Singapore
| | - David Chien Lye
- Department of Infectious Diseases, Communicable Disease Centre, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore
| | - Thuan Tong Tan
- Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore
| | - Jenny G H Low
- Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore
| |
Collapse
|
|
28
|
George J, Newman JM, Klika AK, Miller EM, Tan TL, Parvizi J, Higuera CA. Changes in Antibiotic Susceptibility of Staphylococcus aureus Between the Stages of 2-Stage Revision Arthroplasty. J Arthroplasty 2018; 33:1844-1849. [PMID: 29502963 DOI: 10.1016/j.arth.2018.01.056] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 01/02/2018] [Accepted: 01/22/2018] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Staphylococcus aureus is the predominant cause of periprosthetic joint infection (PJI) and can persist at the time of planned second stage of 2-stage revision arthroplasty, despite antibiotic cement spacer insertion and parenteral antibiotic therapy. Given the rapid emergence of antibiotic resistance, it is important to determine whether the antibiotic susceptibility of microorganisms changes between the stages of a 2-stage revision. METHODS A total of 1614 2-stage revision hip/knee arthroplasties performed for PJI at 2 academic institutions from 2000 to 2015 were identified. S aureus (methicillin susceptible and/or resistant) was isolated by culture in 402 (24.9%) cases during the first stage (resection arthroplasty). S aureus persisted and was cultured in 30 cases (knees = 18, hips = 12) during the second stage. Minimum inhibitory concentrations (MICs), demographics, antibiotic therapy, and surgical history were collected. The MICs at the time of the first-stage and second-stage surgeries were compared. RESULTS Nine (30%) revisions had an increase in vancomycin MIC. Six had an increase from ≤0.5 to 1 μg/mL, 2 had an increase from ≤0.5 to 2 μg/mL, and 1 had an increase from 1 to 2 μg/mL. All of the 9 revisions with an increase in vancomycin MIC had vancomycin in spacer. CONCLUSION Increases in the MICs were observed for vancomycin, the antibiotic widely used in cement spacers, in about one-third of the revisions. Despite the small sample size, the data from this preliminary study raise concern about the potential for emergence of resistant organisms between the stages of a 2-stage revision.
Collapse
Affiliation(s)
- Jaiben George
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Jared M Newman
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Alison K Klika
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Evan M Miller
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Timothy L Tan
- Department of Orthopaedic Surgery, Rothman Institute, Philadelphia, Pennsylvania
| | - Javad Parvizi
- Department of Orthopaedic Surgery, Rothman Institute, Philadelphia, Pennsylvania
| | - Carlos A Higuera
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
29
|
Abulfathi AA, Chirehwa M, Rosenkranz B, Decloedt EH. Evaluation of the Effectiveness of Dose Individualization to Achieve Therapeutic Vancomycin Concentrations. J Clin Pharmacol 2018; 58:1134-1139. [DOI: 10.1002/jcph.1254] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/08/2018] [Indexed: 11/08/2022]
Affiliation(s)
- Ahmed A. Abulfathi
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Maxwell Chirehwa
- Biostatistics Unit; Centre for Evidence Based Health Care (CEHBC); Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Bernd Rosenkranz
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Eric H. Decloedt
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| |
Collapse
|
|
30
|
Bouiller K, Laborde C, Aho SL, Hocquet D, Pechinot A, Le Moing V, Bertrand X, Piroth L, Chirouze C. No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia. Int J Antimicrob Agents 2018; 51:721-726. [DOI: 10.1016/j.ijantimicag.2017.12.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 12/19/2017] [Accepted: 12/28/2017] [Indexed: 10/18/2022]
|
|
31
|
San-Juan R, Viedma E, Chaves F, Lalueza A, Fortún J, Loza E, Pujol M, Ardanuy C, Morales I, de Cueto M, Resino-Foz E, Morales-Cartagena A, Rico A, Romero MP, Orellana MÁ, López-Medrano F, Fernández-Ruiz M, Aguado JM. High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus. Emerg Infect Dis 2018; 22:1057-66. [PMID: 27192097 PMCID: PMC4880091 DOI: 10.3201/eid2206.151709] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Patients infected with these bacteria were more likely to have local endovascular complications. We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications.
Collapse
|
|
32
|
Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus In Vitro. Antimicrob Agents Chemother 2017; 61:AAC.01090-17. [PMID: 28874375 DOI: 10.1128/aac.01090-17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 08/22/2017] [Indexed: 02/07/2023] Open
Abstract
This study investigated the effects of subinhibitory doses of the lipoglycopeptide antibiotic dalbavancin on Staphylococcus aureus toxin production in vitroS. aureus toxin production levels were compared to those seen with the natural glycopeptide antibiotic vancomycin and with representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely affected toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production at subinhibitory concentrations. These findings support the recent success of dalbavancin for treatment of staphylococcal infections.
Collapse
|
|
33
|
Nam EY, Yang SJ, Kim ES, Cho JE, Park KH, Jung SI, Yoon N, Kim DM, Lee CS, Jang HC, Park Y, Lee KS, Kwak YG, Lee JH, Park SY, Hwang JH, Kim M, Song KH, Kim HB. Emergence of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Clinical Isolates Among Daptomycin-Naive Patients in Korea. Microb Drug Resist 2017; 24:534-541. [PMID: 29863982 DOI: 10.1089/mdr.2017.0212] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
This study was conducted to assess emergence of daptomycin-nonsusceptible (DAP-NS) phenotype in DAP-naive patients with invasive Staphylococcus aureus (ISA) infections in Korea. A total of 208 S. aureus clinical isolates were selected from a previous prospective study on ISA infections and evaluated for DAP-NS. Although DAP has never been introduced in Korea, five DAP-NS S. aureus strains (2.4%) were identified among 208 S. aureus strains collected from ISA infections. The DAP-NS phenotype was observed only in methicillin-resistant S. aureus (MRSA) strains, but not in methicillin-susceptible S. aureus strains. One DAP-NS MRSA strain belonged to sequence type 72 (ST72) and four were ST5 MRSA strains, three of which were heteroresistant vancomycin (VAN)-intermediate S. aureus. All these five DAP-NS MRSA strains were from healthcare-associated infections without prior exposure to VAN within 30 days. While the ST72 MRSA strain exhibited DAP-NS phenotype via charge repulsion mechanism, four ST5 DAP-NS S. aureus strains had charge-independent DAP-NS mechanism. None of the five DAP-NS strains displayed significant increase in cell wall thickness, indicating that altered cell wall thickness was not associated with the observed DAP-NS phenotype.
Collapse
Affiliation(s)
- Eun Young Nam
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| | - Soo-Jin Yang
- 3 School of Bioresources and Bioscience, Chung-Ang University , Anseong, Republic of Korea
| | - Eu Suk Kim
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| | - Jeong Eun Cho
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea
| | - Kyung-Hwa Park
- 4 Department of Internal Medicine, Chonnam National University Hospital , Gwangju, Republic of Korea
| | - Sook-In Jung
- 4 Department of Internal Medicine, Chonnam National University Hospital , Gwangju, Republic of Korea
| | - Nara Yoon
- 5 Department of Internal Medicine, Chosun University Hospital , Gwangju, Republic of Korea
| | - Dong-Min Kim
- 5 Department of Internal Medicine, Chosun University Hospital , Gwangju, Republic of Korea
| | - Chang-Seop Lee
- 6 Department of Internal Medicine, Chonbuk National University , Jeonju, Republic of Korea
| | - Hee-Chang Jang
- 7 Department of Internal Medicine, Chonnam National University Hwasun Hospital , Hwasun, Republic of Korea
| | - Yoonseon Park
- 8 Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital , Goyang, Republic of Korea
| | - Kkot Sil Lee
- 9 Department of Internal Medicine, Myongji Hospital , Goyang, Republic of Korea
| | - Yee Gyung Kwak
- 10 Department of Internal Medicine, Inje University Ilsan Paik Hospital , Goyang, Republic of Korea
| | - Jae Hoon Lee
- 11 Department of Internal Medicine, Wonkwang University Hospital , Iksan, Republic of Korea
| | - Seong Yeon Park
- 12 Department of Internal Medicine, Dongguk University Ilsan Hospital , Goyang, Republic of Korea
| | - Joo-Hee Hwang
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| | - Moonsuk Kim
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| | - Kyoung-Ho Song
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| | - Hong Bin Kim
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.,2 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea
| |
Collapse
|
|
34
|
Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin. Clin Orthop Relat Res 2017; 475:1767-1774. [PMID: 28401341 PMCID: PMC5449331 DOI: 10.1007/s11999-017-5302-0] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA). Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered. QUESTIONS/PURPOSES (1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury? METHODS A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During the same period, 5810 patients underwent primary TJA and received cefazolin monotherapy. A chart review was performed to obtain patient characteristics, antibiotic dose and timing of administration, and microbiology data. Adequate vancomycin dosing was defined as 15 mg/kg and within the 125-mg range. Vancomycin levels were calculated at the beginning and end of surgery using pharmacokinetic equations. Levels of 15 mg/L were considered adequate. Logistic regression, chi square tests, and analysis of variance were performed. RESULTS Among primary TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 [2%]) compared with patients receiving cefazolin prophylaxis (62 of 5810 [1%]; adjusted odds ratio, 1.587 [1.004-2.508]; p = 0.048). Ten percent of PJIs in the vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was adequately dosed according to weight-based dosage recommendations. Furthermore, 94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom 64% (1105 of 1726) were underdosed. All patients had vancomycin infusion initiated within 2 hours before incision. A weight-based protocol would have resulted in fewer patients having unacceptably low vancomycin levels (< 15 mg/L) compared with those with actual fixed dosing, both for the beginning of surgery at the time of incision (zero of 1828 [0%] versus 471 of 1828 [26%]; odds ratio, 0.001 [0.000-0.013]; p < 0.001) and at the end of surgery (33 of 1828 [2%] versus 746 of 1828 [41%]; odds ratio, 0.027 [0.019-0.038]; p < 0.001). Between the vancomycin dosage groups, there were no differences in the rate of nephrotoxicity (underdosed: 12 of 1130 [1%], adequately dosed: five of 518 [1%], overdosed: four of 180 [2%], p = 0.363) and acute kidney injury (underdosed: 28 of 1130 [2%], adequately dosed: 10 of 518 [2%], overdosed: six of 180 [3%], p = 0.561). CONCLUSIONS The majority of patients given vancomycin prophylaxis are underdosed according to the weight-based dosage recommendations, and MRSA did not occur in patients who were adequately dosed with vancomycin. Surgeons should thus ensure that their patients are adequately dosed with vancomycin using the recommendation of 15 mg/kg and that the dose of vancomycin is administered in a timely fashion. Furthermore, and based on the findings of this study, we have moved toward limiting the utilization of vancomycin prophylaxis for patients undergoing elective arthroplasty at our institution. LEVEL OF EVIDENCE Level III, therapeutic study.
Collapse
|
|
35
|
Britt NS, Patel N, Shireman TI, El Atrouni WI, Horvat RT, Steed ME. Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia. J Antimicrob Chemother 2016; 72:535-542. [PMID: 27999028 DOI: 10.1093/jac/dkw453] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 09/18/2016] [Accepted: 09/23/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Previous data have demonstrated the clinical importance of vancomycin MIC values in Staphylococcus aureus bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown. OBJECTIVES To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB. METHODS This was a retrospective cohort study of patients with SAB, excluding treatment <48 h or polymicrobial bacteraemia. The primary outcome was clinical failure (composite of 30 day mortality, non-resolving signs and symptoms, and 60 day recurrence). Vancomycin MIC and MBC were determined by broth microdilution. The association between VT (MBC/MIC ≥32) and clinical failure was evaluated by multivariable Poisson regression. RESULTS Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (n = 41/60) versus 40.6% (n = 67/165); P < 0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; P < 0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (n = 125, risk ratio, 1.67; 95% CI, 1.20-2.32; P = 0.002); methicillin resistant (n = 100, risk ratio, 1.69; 95% CI, 1.14-2.51; P = 0.010)]. Among methicillin-susceptible SAB cases treated with β-lactam therapy, VT remained associated with clinical failure (risk ratio, 1.77; 95% CI, 1.19-2.61; P = 0.004). CONCLUSIONS VT was associated with clinical failure in SAB, irrespective of methicillin susceptibility or definitive treatment. VT may decrease the effectiveness of cell-wall-active therapy or be a surrogate marker of some other pathogen-specific factor associated with poor outcomes. Future research should evaluate if bactericidal non-cell-wall-active agents improve outcomes in VT SAB.
Collapse
Affiliation(s)
- Nicholas S Britt
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA.,Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Nimish Patel
- Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA
| | - Theresa I Shireman
- Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Wissam I El Atrouni
- Department of Medicine, Division of Infectious Diseases, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Rebecca T Horvat
- Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Molly E Steed
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA
| |
Collapse
|
|
36
|
Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother 2016; 60:3070-5. [PMID: 26953202 DOI: 10.1128/aac.02714-15] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 03/03/2016] [Indexed: 12/13/2022] Open
Abstract
While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) and mortality were determined by χ(2) and multivariable Poisson regression. Overall mortality in this cohort (n = 53) was 20.8% (n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B.
Collapse
|
|
37
|
Gjini E, Brito PH. Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment. PLoS Comput Biol 2016; 12:e1004857. [PMID: 27078624 PMCID: PMC4831758 DOI: 10.1371/journal.pcbi.1004857] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/09/2016] [Indexed: 12/18/2022] Open
Abstract
Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes.
Collapse
Affiliation(s)
- Erida Gjini
- Instituto Gulbenkian de Ciência, Oeiras, Portugal
- * E-mail:
| | - Patricia H. Brito
- Instituto Gulbenkian de Ciência, Oeiras, Portugal
- Nova Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
| |
Collapse
|
|
38
|
Screening for Intermediately Vancomycin-Susceptible and Vancomycin-Heteroresistant Staphylococcus aureus by Use of Vancomycin-Supplemented Brain Heart Infusion Agar Biplates: Defining Growth Interpretation Criteria Based on Gold Standard Confirmation. J Clin Microbiol 2015; 53:3543-6. [PMID: 26311860 DOI: 10.1128/jcm.01620-15] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 08/22/2015] [Indexed: 01/23/2023] Open
Abstract
BHI agars supplemented with vancomycin 4 (BHI-V4) and 3 (BHI-V3) mg/liter have been proposed for screening vancomycin intermediately susceptible Staphylococcus aureus (VISA) and heteroresistant (hVISA) phenotypes, respectively, but growth interpretation criteria have not been established. We reviewed the growth results (CFU) during population analysis profile-area under the curve (PAP-AUC) of consecutive methicillin-resistant Staphylococcus aureus (MRSA) blood isolates, which were saved intermittently between 1996 and 2012. CFU counts on BHI-V4 and BHI-V3 plates were stratified according to PAP-AUC interpretive criteria: <0.90 (susceptible [S-MRSA]), 0.90 to 1.3 (hVISA), and >1.3 (VISA). CFU cutoffs that best predict VISA and hVISA were determined with the use of receiver operating characteristic (ROC) curves. Mu3, Mu50, and methicillin-susceptible S. aureus (MSSA) controls were included. We also prospectively evaluated manufacturer-made BHI-V3/BHI-V4 biplates for screening of 2010-2012 isolates. The PAP-AUC of 616 clinical samples was consistent with S-MRSA, hVISA, and VISA in 550 (89.3%), 48 (7.8%), and 18 (2.9%) instances, respectively. For VISA screening on BHI-V4, a cutoff of 2 CFU/droplet provided 100% sensitivity and 97.7% specificity. To distinguish VISA from hVISA, a cutoff of 16 CFU provided 83.3% sensitivity and 94.7% specificity; the specificity was lowered to 89.5% with a 12-CFU cutoff. For detecting hVISA/VISA on BHI-V3, a 2-CFU/droplet cutoff provided 98.5% sensitivity and 93.8% specificity. These results suggest that 2-CFU/droplet cutoffs on BHI-V4 and BHI-V3 best approximate VISA and hVISA gold standard confirmation, respectively, with minimal overlap in samples with borderline PAP-AUC. Simultaneous screening for VISA/hVISA on manufacturer-made BHI-V4/BHI-V3 biplates is easy to standardize and may reduce the requirement for PAP-AUC confirmation.
Collapse
|
|
39
|
Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol 2015; 8:635-48. [PMID: 26289222 DOI: 10.1586/17512433.2015.1060124] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In neonates, vancomycin, a narrow-spectrum antibiotic, is the first choice of treatment of late-onset sepsis predominantly caused by Gram-positive bacteria (coagulase-negative staphylococci and enterococci). Although it has been used for >50 years, prescribing the right dose and dosing regimen remains a challenge in neonatal intensive care units for many reasons including high pharmacokinetic variability, increase in the minimal inhibition concentration against staphylococci, lack of consensus on dosing regimen and way of administration (continuous or intermittent), duration of treatment, use of therapeutic drug monitoring, limited data on short- and long-term toxicity, risk of mutant selection and errors of administration linked to concentrated formulations. This article highlights and discusses future research directions, with specific attention given to dosing optimization of vancomycin, including the advantages of modeling and simulation approaches.
Collapse
Affiliation(s)
- Evelyne Jacqz-Aigrain
- a 1 Department of Paediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, AP-HP, Paris, France
| | | | | | | | | |
Collapse
|
|
40
|
The times they are a-changin': new antibacterials for skin and skin structure infections. Am J Clin Dermatol 2015; 16:137-46. [PMID: 25906205 DOI: 10.1007/s40257-015-0125-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Twenty-one agents are approved by the US Food and Drug Administration (FDA) for the therapy of skin and soft tissue infections. Of these, the five newest agents, tedizolid, telavancin, oritavancin, dalbavancin, and ceftaroline, are active against and "non-inferior" to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Oritavancin is indicated as a single-dose intravenous regimen, while dalbavancin is a two-dose intravenous regimen given 1 week apart. Telavancin has multiple mechanisms of action. A 6-day regimen of once-daily intravenous or oral dose of tedizolid was compared with 10 days of linezolid and found to be "non-inferior" and have fewer side effects. Ceftaroline has not only MRSA activity but also activity against Escherichia coli and Klebsiella spp. We review the spectra of activity of these new agents, their clinical trials and their therapeutic efficacy, noting differences in their dosing schedules, in vitro activities and costs as potential determinants for appropriate utilization.
Collapse
|
|
41
|
Morales-Cartagena A, Lalueza A, López-Medrano F, Juan RS, Aguado JM. Treatment of methicillin-resistant Staphylococcus aureus infections: Importance of high vancomycin minumum inhibitory concentrations. World J Clin Infect Dis 2015; 5:14-29. [DOI: 10.5495/wjcid.v5.i2.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 10/30/2014] [Accepted: 03/09/2015] [Indexed: 02/06/2023] Open
Abstract
Staphylococcus aureus (SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threatening systemic infections. The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration (MIC) (dubbed the MIC “creep”). In this way, the emergence of vancomycin-intermediate SA (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant SA. These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach. Ultimately, various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range (i.e., MIC = 2 μg/mL). These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use, both in methicillin-resistant SA and in methicillin-sensitive SA. The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains, and the different optimal treatment options known.
Collapse
|
|
42
|
Park MJ, Kim HS, Kim HS, Kim JS, Song W, Kim MY, Lee YK, Kang HJ. Accessory Gene Regulator Polymorphism and Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus aureus. Ann Lab Med 2015; 35:399-403. [PMID: 26131410 PMCID: PMC4446577 DOI: 10.3343/alm.2015.35.4.399] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 02/09/2015] [Accepted: 04/25/2015] [Indexed: 11/19/2022] Open
Abstract
Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL presents a high rate of therapeutic failure in response to vancomycin. In addition, polymorphism in accessory gene regulator (agr) is associated with vancomycin therapeutic effects. The association between agr polymorphism and vancomycin MICs was investigated in MRSA isolates. Methods Agr group-specific PCR was conducted on 118 MRSA bloodstream isolates. Vancomycin susceptibility tests were conducted, while E-test GRD (bioMérieux SA, France) was used to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Results Of the 118 MRSA isolates, 59 (50.0%), 43 (36.4%), and 10 (8.5%) isolates belonged to agr group I, II, and III, respectively. Six isolates could not be classified. Twenty-six, 73, and 19 isolates presented a vancomycin MIC of 2, 1, and 0.5 µg/mL, respectively. Nine (34.6%), 14 (53.8%), and 2 (7.7%) isolates with MICs of 2 µg/mL belonged to agr group I, II, and III, respectively. Thirty-seven (50.6%), 26 (35.6%), and 6 (8.2%) isolates with MICs of 1 µg/mL belonged to agr group I, II, and III, respectively. Thirteen (68.4%), 3 (15.8%), and 2 (10.5%) isolates with MICs of 0.5 µg/mL belonged to agr group I, II, and III, respectively. The agr group II presented more isolates with MIC of 2 µg/mL (32.6%) than the agr non-group II (16%). Four isolates tested positive for hVISA. Three of them belonged to agr group II. Conclusions MRSA isolates with vancomycin MIC of 2 µg/mL were more common in agr group II than in agr non-group II.
Collapse
Affiliation(s)
- Min-Jeong Park
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Han-Sung Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Hyun Soo Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Jae-Seok Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Wonkeun Song
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Mi Young Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Young Kyung Lee
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Hee Jung Kang
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| |
Collapse
|
|
43
|
Cázares-Domínguez V, Ochoa SA, Cruz-Córdova A, Rodea GE, Escalona G, Olivares AL, Olivares-Trejo JDJ, Velázquez-Guadarrama N, Xicohtencatl-Cortes J. Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates. Front Microbiol 2015; 6:369. [PMID: 25999924 PMCID: PMC4419724 DOI: 10.3389/fmicb.2015.00369] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 04/11/2015] [Indexed: 01/08/2023] Open
Abstract
Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus. Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors.
Collapse
Affiliation(s)
- Vicenta Cázares-Domínguez
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| | - Sara A Ochoa
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| | - Ariadnna Cruz-Córdova
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| | - Gerardo E Rodea
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| | - Gerardo Escalona
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| | - Alma L Olivares
- Laboratorio de Infectología, Hospital Infantil de México Federico Gómez México DF, Mexico
| | | | | | - Juan Xicohtencatl-Cortes
- Laboratorio de Investigación en Bacteriología Intestinal, Hospital Infantil de México Federico Gómez México DF, Mexico
| |
Collapse
|
|
44
|
¿Impacto de la concentración mínima inhibitoria de vancomicina o incorrecto manejo terapéutico en el fracaso clínico por Staphylococcus aureus resistentes a meticilina? An Pediatr (Barc) 2015; 82:373-4. [DOI: 10.1016/j.anpedi.2014.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 05/26/2014] [Accepted: 07/15/2014] [Indexed: 11/19/2022] Open
|
|
45
|
Singh A, Prasad KN, Rai RP, Singh SK, Rahman M, Tripathi A, Srivastava JK. Glycopeptide and daptomycin susceptibility trends among clinical isolates of methicillin-resistant Staphylococcus aureus in a tertiary care center in North India. J Infect Public Health 2015; 8:341-5. [PMID: 25797814 DOI: 10.1016/j.jiph.2015.02.002] [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: 10/14/2014] [Revised: 12/31/2014] [Accepted: 02/13/2015] [Indexed: 11/17/2022] Open
Abstract
Increased vancomycin minimum inhibitory concentration (MIC) levels in Staphylococcus aureus and their association with vancomycin treatment failure are well-known problems. Few studies have recognized progressive increases in glycopeptide MIC levels for S. aureus strains in recent years. This study determined glycopeptide and daptomycin susceptibility among methicillin resistant S. aureus (MRSA) strains. A total of 776 clinical isolates of MRSA recovered from 2009 to 2012 were studied for glycopeptide and daptomycin susceptibility using the E-test method. The vancomycin MIC geometric mean (GM) of the MRSA isolates was 0.923, 0.944, 1.134 and 1.294 mg/L in the years 2009, 2010, 2011 and 2012, respectively, and the trend significantly increased over the years (P < 0.0001). Similarly, the teicoplanin MIC GM was 1.47, 1.49, 1.8 and 2.04 mg/L in the years from 2009 to 2012, respectively (P < 0.0001). MIC shifts were not found for daptomycin (P > 0.232). A significant increase in the MIC for glycopeptides was observed among the clinical MRSA isolates at our center over a 4-year period. However, the daptomycin MIC did not increase in the observed MRSA isolates.
Collapse
Affiliation(s)
- Avinash Singh
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow, Uttar Pradesh, India
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
| | - Ravi P Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Satyendra K Singh
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Mohibur Rahman
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Aparna Tripathi
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Janmejai K Srivastava
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow, Uttar Pradesh, India
| |
Collapse
|
|
46
|
In vitro bactericidal activity of 4- and 5-chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA. BIOMED RESEARCH INTERNATIONAL 2015; 2015:349534. [PMID: 25692135 PMCID: PMC4321674 DOI: 10.1155/2015/349534] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 09/25/2014] [Accepted: 10/08/2014] [Indexed: 11/18/2022]
Abstract
A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log10 CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log10 CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.
Collapse
|
|
47
|
MacVane SH, So W, Nicolau DP, Kuti JL. In vitro activity of human-simulated epithelial lining fluid exposures of ceftaroline, ceftriaxone, and vancomycin against methicillin-susceptible and -resistant Staphylococcus aureus. Antimicrob Agents Chemother 2014; 58:7520-6. [PMID: 25288076 PMCID: PMC4249498 DOI: 10.1128/aac.03742-14] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 09/30/2014] [Indexed: 12/29/2022] Open
Abstract
Staphylococcus aureus, including methicillin-susceptible (MSSA) and -resistant (MRSA) strains, is an important pathogen of bacterial pneumonia. As antibiotic concentrations at the site of infection are responsible for killing, we investigated the activity of human-simulated epithelial lining fluid (ELF) exposures of three antibiotics (ceftaroline, ceftriaxone, and vancomycin) commonly used for treatment of S. aureus pneumonia. An in vitro pharmacodynamic model was used to simulate ELF exposures of vancomycin (1 g every 12 h [q12h]), ceftaroline (600 mg q12h and q8h), and ceftriaxone (2 g q24h and q12h). Four S. aureus isolates (2 MSSA and 2 MRSA) were evaluated over 72 h with a starting inoculum of ∼ 10(6) CFU/ml. Time-kill curves were constructed, and microbiological response (change in log10 CFU/ml from 0 h and the area under the bacterial killing and regrowth curve [AUBC]) was assessed in duplicate. The change in 72-h log10 CFU/ml was largest for ceftaroline q8h (reductions of >3 log10 CFU/ml against all strains). This regimen also achieved the lowest AUBC against all organisms (P < 0.05). Vancomycin produced reliable bacterial reductions of 0.9 to 3.3 log10 CFU/ml, while the activity of ceftaroline q12h was more variable (reductions of 0.2 to 2.3 log10 CFU/ml against 3 of 4 strains). Both regimens of ceftriaxone were poorly active against MSSA tested (0.1 reduction to a 1.8-log10 CFU/ml increase). Against these S. aureus isolates, ELF exposures of ceftaroline 600 mg q8h exhibited improved antibacterial activity compared with ceftaroline 600 mg q12h and vancomycin, and therefore, this q8h regimen deserves further evaluation for the treatment of bacterial pneumonia. These data also suggest that ceftriaxone should be avoided for S. aureus pneumonia.
Collapse
Affiliation(s)
- Shawn H MacVane
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA
| | - Wonhee So
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA
| | - David P Nicolau
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA
| | - Joseph L Kuti
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA
| |
Collapse
|
|
48
|
Paladino JA, Jacobs DM, Shields RK, Taylor J, Bader J, Adelman MH, Wilton GJ, Crane JK, Schentag JJ. Use of ceftaroline after glycopeptide failure to eradicate meticillin-resistant Staphylococcus aureus bacteraemia with elevated vancomycin minimum inhibitory concentrations. Int J Antimicrob Agents 2014; 44:557-63. [PMID: 25282169 DOI: 10.1016/j.ijantimicag.2014.07.024] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 07/08/2014] [Accepted: 07/14/2014] [Indexed: 11/19/2022]
Abstract
Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2-4 μg/mL). This multicentre, retrospective, case-control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3-15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3-7.5 days) vs. 8 days (IQR, 5.8-19.5 days); P=0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P=0.06) and 6% vs. 38% (P=0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.
Collapse
Affiliation(s)
- Joseph A Paladino
- University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA; Erie County Medical Center, 462 Grider St., Buffalo, NY 14215, USA.
| | - David M Jacobs
- University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA
| | - Ryan K Shields
- University of Pittsburgh, Department of Medicine, 3601 Fifth Ave., Falk Medical Building, Suite 3A, Pittsburgh, PA 15213, USA
| | - Jerusha Taylor
- Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA
| | - Justin Bader
- University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA
| | | | - Greg J Wilton
- CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA
| | - John K Crane
- Erie County Medical Center, 462 Grider St., Buffalo, NY 14215, USA; University at Buffalo School of Medicine, 326 Biomedical Research Building, 3435 Main St., Buffalo, NY 14214, USA
| | - Jerome J Schentag
- University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA
| |
Collapse
|
|
49
|
Pinheiro L, Brito CI, Pereira VC, Oliveira AD, Camargo CH, Cunha MDLRDSD. Reduced susceptibility to vancomycin and biofilm formation in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures. Mem Inst Oswaldo Cruz 2014; 109:871-8. [PMID: 25410990 PMCID: PMC4296491 DOI: 10.1590/0074-0276140120] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Accepted: 09/10/2014] [Indexed: 11/21/2022] Open
Abstract
This study aimed to correlate the presence of ica genes, biofilm
formation and antimicrobial resistance in 107 strains of Staphylococcus
epidermidis isolated from blood cultures. The isolates were analysed to
determine their methicillin resistance, staphylococcal cassette chromosome
mec (SCCmec) type, ica genes
and biofilm formation and the vancomycin minimum inhibitory concentration (MIC) was
measured for isolates and subpopulations growing on vancomycin screen agar. The
mecA gene was detected in 81.3% of the S.
epidermidis isolated and 48.2% carried SCCmec type III.
The complete icaADBC operon was observed in 38.3% of the isolates;
of these, 58.5% produced a biofilm. Furthermore, 47.7% of the isolates grew on
vancomycin screen agar, with an increase in the MIC in 75.9% of the isolates.
Determination of the MIC of subpopulations revealed that 64.7% had an MIC ≥ 4 μg
mL-1, including 15.7% with an MIC of 8 μg mL-1 and 2% with
an MIC of 16 μg mL-1. The presence of the icaADBC operon,
biofilm production and reduced susceptibility to vancomycin were associated with
methicillin resistance. This study reveals a high level of methicillin resistance,
biofilm formation and reduced susceptibility to vancomycin in subpopulations of
S. epidermidis. These findings may explain the selection of
multidrug-resistant isolates in hospital settings and the consequent failure of
antimicrobial treatment.
Collapse
Affiliation(s)
- Luiza Pinheiro
- Laboratório de Microbiologia, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Carla Ivo Brito
- Laboratório de Microbiologia, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Valéria Cataneli Pereira
- Laboratório de Microbiologia, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Adilson de Oliveira
- Laboratório de Microbiologia, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - Carlos Henrique Camargo
- Laboratório de Microbiologia, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | | |
Collapse
|
|
50
|
Painter KL, Krishna A, Wigneshweraraj S, Edwards AM. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia? Trends Microbiol 2014; 22:676-85. [PMID: 25300477 DOI: 10.1016/j.tim.2014.09.002] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 09/10/2014] [Accepted: 09/12/2014] [Indexed: 11/18/2022]
Abstract
Staphylococcus aureus is a major cause of bacteremia, which frequently results in serious secondary infections such as infective endocarditis, osteomyelitis, and septic arthritis. The ability of S. aureus to cause such a wide range of infections has been ascribed to its huge armoury of different virulence factors, many of which are under the control of the quorum-sensing accessory gene regulator (Agr) system. However, a significant fraction of S. aureus bacteremia cases are caused by agr-defective isolates, calling into question the role of Agr in invasive staphylococcal infections. This review draws on recent work to define the role of Agr during bacteremia and explain why the loss of this major virulence regulator is sometimes a price worth paying for S. aureus.
Collapse
Affiliation(s)
- Kimberley L Painter
- Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College, Armstrong Road, London SW7 2AZ, UK
| | - Aishwarya Krishna
- Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College, Armstrong Road, London SW7 2AZ, UK
| | - Sivaramesh Wigneshweraraj
- Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College, Armstrong Road, London SW7 2AZ, UK
| | - Andrew M Edwards
- Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College, Armstrong Road, London SW7 2AZ, UK.
| |
Collapse
|