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Bahri F, Boussena A, Szumny A, Bahri Y, Bahri EM, Figiel A, Juszczyk P. Use of Haloxylon scoparium Against Multidrug-Resistant Bacteria from Urinary Tract Infections. Antibiotics (Basel) 2025; 14:471. [PMID: 40426538 PMCID: PMC12108462 DOI: 10.3390/antibiotics14050471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/25/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND The emergence of multidrug-resistant bacteria in the urinary tract and the decrease in the efficacy of antibiotics prompted us to evaluate the antibacterial activity of the methanolic extract of the aerial parts of Haloxylon scoparium against six isolated (MDR) bacteria. METHODS Phenolic compound profiling of the extract of interest was performed by HPLC-DAD. Acute oral toxicity was tested in vivo. The antibiotic susceptibility of the isolates was assessed against 23 antibiotics using the disk diffusion method. The identification of the isolates was performed by 16S rRNA gene sequencing. The antibacterial activity of the extract was assessed using agar well diffusion, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs) methods. RESULTS Phenolic compound profiling of the extract revealed that epicatechin (85%) was the major compound. The extract also showed no symptoms of toxicity, adverse effects, or mortality in mice at the recommended dose. Overall, the extract at 200 µg/mL was effective against all isolates. The zones of inhibition ranged from 9.25 to 19.5 mm. Gram-positive S. aureus bacteria recorded the highest inhibitory effect with 19.5 mm against the five Gram-negative bacteria (9.25-17.25 mm). The MIC of the extracts against clinical isolates ranged from 50 to 100 µg/mL. The extract was bactericidal against S. aureus, E. coli, E. ludwigii, and K. pneumoniae with an MBC of 100, 100, 200, and 200 µg/mL, respectively. CONCLUSIONS The results conclude that the extract could be an effective source of antimicrobial agents for the treatment of urinary tract infections caused by MDR bacteria.
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Affiliation(s)
- Fouad Bahri
- Laboratory of Microbiology and Plant Biology, Faculty of Nature and Life Sciences, Abdelhamid Ibn Badis University, BP 188/227, Mostaganem 27000, Algeria; (F.B.); (A.B.); (Y.B.); (E.-M.B.)
| | - Abdelhadi Boussena
- Laboratory of Microbiology and Plant Biology, Faculty of Nature and Life Sciences, Abdelhamid Ibn Badis University, BP 188/227, Mostaganem 27000, Algeria; (F.B.); (A.B.); (Y.B.); (E.-M.B.)
| | - Antoni Szumny
- Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Sciences, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375 Wroclaw, Poland
| | - Youcef Bahri
- Laboratory of Microbiology and Plant Biology, Faculty of Nature and Life Sciences, Abdelhamid Ibn Badis University, BP 188/227, Mostaganem 27000, Algeria; (F.B.); (A.B.); (Y.B.); (E.-M.B.)
| | - El-Mokhtar Bahri
- Laboratory of Microbiology and Plant Biology, Faculty of Nature and Life Sciences, Abdelhamid Ibn Badis University, BP 188/227, Mostaganem 27000, Algeria; (F.B.); (A.B.); (Y.B.); (E.-M.B.)
| | - Adam Figiel
- Institute of Agricultural Engineering, Faculty of Life Sciences and Technology, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland;
| | - Piotr Juszczyk
- Department of Biotechnology and Food Microbiology, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, 51-630 Wrocław, Poland;
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Gray HA, Biggs PJ, Midwinter AC, Rogers LE, Fayaz A, Akhter RN, Burgess SA. Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli from humans and a river in Aotearoa New Zealand. Microb Genom 2025; 11:001341. [PMID: 39791259 PMCID: PMC11718517 DOI: 10.1099/mgen.0.001341] [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: 05/08/2024] [Accepted: 12/03/2024] [Indexed: 01/12/2025] Open
Abstract
In Aotearoa New Zealand, urinary tract infections in humans are commonly caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. This group of antimicrobial-resistant bacteria are often multidrug resistant. However, there is limited information on ESBL-producing E. coli found in the environment and their link with human clinical isolates. In this study, we examined the genetic relationship between environmental and human clinical ESBL-producing E. coli and isolates collected in parallel within the same area over 14 months. Environmental samples were collected from treated effluent, stormwater and multiple locations along an Aotearoa New Zealand river. Treated effluent, stormwater and river water sourced downstream of the treated effluent outlet were the main samples that were positive for ESBL-producing E. coli (7/14 samples, 50.0%; 3/6 samples, 50%; and 15/28 samples, 54%, respectively). Whole-genome sequence comparison was carried out on 307 human clinical and 45 environmental ESBL-producing E. coli isolates. Sequence type 131 was dominant for both clinical (147/307, 47.9%) and environmental isolates (11/45, 24.4%). Only one ESBL gene was detected in each isolate. Among the clinical isolates, the most prevalent ESBL genes were bla CTX-M-27 (134/307, 43.6%) and bla CTX-M-15 (134/307, 43.6%). Among the environmental isolates, bla CTX-M-15 (28/45, 62.2%) was the most prevalent gene. A core SNP analysis of these isolates suggested that some strains were shared between humans and the local river. These results highlight the importance of understanding different transmission pathways for the spread of ESBL-producing E. coli.
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Affiliation(s)
- Holly A. Gray
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Patrick J. Biggs
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
- School of Food Technology and Natural Sciences, Massey University, Palmerston North, New Zealand
- New Zealand Food Safety Science and Research Centre, Massey University, Palmerston North, New Zealand
| | - Anne C. Midwinter
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Lynn E. Rogers
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Ahmed Fayaz
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Rukhshana N. Akhter
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Sara A. Burgess
- EpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand
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Artero A, López-Cruz I, Aguilera JA, Piles L, Artero S, Eiros JM, Alberola J, Madrazo M. Recurrent Urinary Tract Infections in Older Adults Requiring Hospitalization in an Internal Medicine Ward. Microorganisms 2024; 12:2114. [PMID: 39597504 PMCID: PMC11596791 DOI: 10.3390/microorganisms12112114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/16/2024] [Accepted: 10/16/2024] [Indexed: 11/29/2024] Open
Abstract
Urinary tract infection (UTI) is a common cause of recurrent infections, especially among young women, but also in patients with infections related to the insertion of urological devices. The aim of this study was to determine the recurrent UTI readmission rate among older patients and the risk factors for recurrent UTI in a prospective cohort of patients admitted to the hospital with community-acquired UTI. We assessed the frequency of recurrent UTIs over a one-year follow-up period after discharge and compared the clinical and epidemiological characteristics between cases with and without recurrences. Out of a total of 462 patients included in this study, 35 (7.6%) had a readmission due to UTI. The patients in the overall series had a median age of 78 (69-86) years, and 50% were women. Recurrent UTIs were associated with healthcare-associated UTIs (OR 2.8, 95% CI 1.1-6.9) and Pseudomonas aeruginosa infections (OR 2.7, 95% CI 1.1-7.2) according to multivariate analysis. Patients with recurrent UTIs experienced longer hospital stays, with no significant difference in mortality rates. Half of the recurrent UTIs were caused by the same microorganisms as those in primary UTIs, but the prolonged period up to recurrence, with a median of 4 months, suggests that they were mostly reinfections. In conclusion, elderly patients admitted to the hospital with complicated UTIs had a low long-term risk of recurrent UTIs. However, this risk was higher in patients with healthcare-associated infection criteria and in those with P. aeruginosa UTIs. Identifying these risk groups may aid in the early detection of recurrent UTIs.
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Affiliation(s)
- Arturo Artero
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
| | - Ian López-Cruz
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
| | - Juan Alberto Aguilera
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
| | - Laura Piles
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
| | - Silvia Artero
- Gregorio Marañón University Hospital, 28007 Madrid, Spain;
| | - José María Eiros
- Rio Hortega University Hospital, Universidad de Valladolid, 47012 Valladolid, Spain;
| | - Juan Alberola
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
| | - Manuel Madrazo
- Doctor Peset University Hospital, Universitat de València, 46017 Valencia, Spain; (A.A.); (I.L.-C.); (J.A.A.); (L.P.); (M.M.)
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Hanson BS, Hailemariam A, Yang Y, Mohamed F, Donati GL, Baker D, Sacchettini J, Cai JJ, Subashchandrabose S. Identification of a copper-responsive small molecule inhibitor of uropathogenic Escherichia coli. J Bacteriol 2024; 206:e0011224. [PMID: 38856220 PMCID: PMC11270900 DOI: 10.1128/jb.00112-24] [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: 03/14/2024] [Accepted: 05/10/2024] [Indexed: 06/11/2024] Open
Abstract
Urinary tract infections (UTIs) are a major global health problem and are caused predominantly by uropathogenic Escherichia coli (UPEC). UTIs are a leading cause of prescription antimicrobial use. Incessant increase in antimicrobial resistance in UPEC and other uropathogens poses a serious threat to the current treatment practices. Copper is an effector of nutritional immunity that impedes the growth of pathogens during infection. We hypothesized that copper would augment the toxicity of select small molecules against bacterial pathogens. We conducted a small molecule screening campaign with a library of 51,098 molecules to detect hits that inhibit a UPEC ΔtolC mutant in a copper-dependent manner. A molecule, denoted as E. coli inhibitor or ECIN, was identified as a copper-responsive inhibitor of wild-type UPEC strains. Our gene expression and metal content analysis results demonstrate that ECIN works in concert with copper to exacerbate Cu toxicity in UPEC. ECIN has a broad spectrum of activity against pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Subinhibitory levels of ECIN eliminate UPEC biofilm formation. Transcriptome analysis of UPEC treated with ECIN reveals induction of multiple stress response systems. Furthermore, we demonstrate that L-cysteine rescues the growth of UPEC exposed to ECIN. In summary, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC.IMPORTANCEUrinary tract infection (UTI) is a ubiquitous infectious condition affecting millions of people annually. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI. However, UTIs are becoming increasingly difficult to resolve with antimicrobials due to increased antimicrobial resistance in UPEC and other uropathogens. Here, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC. In addition to E. coli, this small molecule also inhibits pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus.
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Affiliation(s)
- Braden S Hanson
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - Amanuel Hailemariam
- Department of Biochemistry and Biophysics, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, USA
| | - Yongjian Yang
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - Faras Mohamed
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - George L Donati
- Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Dwight Baker
- Department of Biochemistry and Biophysics, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, USA
| | - James Sacchettini
- Department of Biochemistry and Biophysics, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, USA
| | - James J Cai
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - Sargurunathan Subashchandrabose
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
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Henkel R. Leukocytospermia and/or Bacteriospermia: Impact on Male Infertility. J Clin Med 2024; 13:2841. [PMID: 38792382 PMCID: PMC11122306 DOI: 10.3390/jcm13102841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/07/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Infertility is a globally underestimated public health concern affecting almost 190 million people, i.e., about 17.5% of people during their lifetime, while the prevalence of male factor infertility is about 7%. Among numerous other causes, the prevalence of male genital tract infections reportedly ranges between 10% and 35%. Leukocytospermia is found in 30% of infertile men and up to 20% in fertile men. Bacterial infections cause an inflammatory response attracting leukocytes, which produce reactive oxygen species (ROS) and release cytokines, both of which can cause damage to sperm, rendering them dysfunctional. Although leukocytospermia and bacteriospermia are both clinical conditions that can negatively affect male fertility, there is still debate about their impact on assisted reproduction outcomes and management. According to World Health Organization (WHO) guidelines, leukocytes should be determined by means of the Endtz test or with monoclonal antibodies against CD15, CD68 or CD22. The cut-off value proposed by the WHO is 1 × 106 peroxidase-positive cells/mL. For bacteria, Gram staining and semen culture are regarded as the "gold standard", while modern techniques such as PCR and next-generation sequencing (NGS) are allowing clinicians to detect a wider range of pathogens. Whereas the WHO manual does not specify a specific value as a cut-off for bacterial contamination, several studies consider semen samples with more than 103 colony-forming units (cfu)/mL as bacteriospermic. The pathogenic mechanisms leading to sperm dysfunction include direct interaction of bacteria with the male germ cells, bacterial release of spermatotoxic substances, induction of pro-inflammatory cytokines and ROS, all of which lead to oxidative stress. Clinically, bacterial infections, including "silent" infections, are treatable, with antibiotics being the treatment of choice. Yet, non-steroidal antiphlogistics or antioxidants should also be considered to alleviate inflammatory lesions and improve semen quality. In an assisted reproduction set up, sperm separation techniques significantly reduce the bacterial load in the semen. Nonetheless, contamination of the semen sample with skin commensals should be prevented by applying relevant hygiene techniques. In patients where leukocytospermia is detected, the causes (e.g. infection, inflammation, varicocele, smoking, etc.) of the leukocyte infiltration have to be identified and addressed with antibiotics, anti-inflammatories or antioxidants in cases where high oxidative stress levels are detected. However, no specific strategy is available for the management of leukocytospermia. Therefore, the relationship between bacteriospermia and leukocytospermia as well as their specific impact on functional sperm parameters and reproductive outcome variables such as fertilization or clinical pregnancy must be further investigated. The aim of this narrative review is to provide an update on the current knowledge on leukocytospermia and bacteriospermia and their impact on male fertility.
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Affiliation(s)
- Ralf Henkel
- LogixX Pharma Ltd., Merlin House, Brunel Road, Theale, Reading RG7 4AB, UK;
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0HS, UK
- Department of Medical Bioscience, University of the Western Cape, Bellville 7535, South Africa
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Getie M, Gebre-Selassie S, Getu Y, Birara S, Tiruneh C, Abebaw A, Akelew Y, Abeje G, Enkobahry A. Bacterial profile and extended spectrum beta lactamase screening of urinary tract infection among asymptomatic and symptomatic pregnant women attending antenatal care in ALERT Hospital, Addis Ababa, Ethiopia. SAGE Open Med 2023; 11:20503121231197587. [PMID: 37933290 PMCID: PMC10625732 DOI: 10.1177/20503121231197587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 08/10/2023] [Indexed: 11/08/2023] Open
Abstract
Introduction The occurrence of extended spectrum beta lactamase-producing uropathogens, especially in pregnant women can result in life-threatening condition and morbidity for both the mother and the newborn due to very limited drug options for treatment of these pathogens. The aim of this study was to determine the bacterial profile, associated factors, and their antimicrobial susceptibility patterns and to identify extended spectrum beta lactamase-producing bacterial uropathogens. Methods A hospital-based cross-sectional study was conducted from July to September 2018 on a total of 177 pregnant women with and without symptoms of urinary tract infection at ALERT Hospital, Addis Ababa, Ethiopia. From these study participants, 72 have symptoms, whereas 105 have no symptoms. All urine samples were inoculated onto cysteine lactose electrolyte deficient medium and MacConkey agar. Colonies were counted to check the presence of significant bacteriuria. Pure isolates of bacterial pathogen were characterized and identified at species level by colony morphology, gram stain, and standard biochemical procedures. All Gram-negative isolates were put into Muller-Hinton agar plates for antibiotic susceptibility test by Kirby-Bauer disc diffusion technique. Extended spectrum beta lactamase was detected using double-disk synergy methods on Muller-Hinton agar. The data were double entered into epidemiological Information system and analyzed using Statistical Package for Social Science version 26. Results The overall proportion of urinary tract infection among pregnant women was 14.7% (n = 26/177). Klebsiella pneumoniae was the predominant bacterial etiologic agent of urinary tract infection 26.9% (n = 7/26). The proportion of extended spectrum beta lactamase among Gram-negative isolates was 50% (n = 6/12). Among extended spectrum beta lactamase-producing isolates (100%), all are resistance to amikacin and gentamicin while intermediate level resistance rate of 66.7% was observed among trimethoprim-sulphamethoxazole. They were susceptible for some limited drugs, and these were Nitrofurantoin (83.3%) and Chloramphenicol (83.3%). Conclusions Majority of extended spectrum beta lactamase-producing isolates exhibited co-resistance to other commonly prescribed antibiotics. This indicates that the option of treatment for these pathogens rapidly decreased from time to time which results serious life-threatening conditions, especially in mother and newborn unless the appropriate measure is taken.
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Affiliation(s)
- Molla Getie
- Departments of Medical Laboratory Science, Injibara University, Injibara, Ethiopia
| | - Solomon Gebre-Selassie
- Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yemeserach Getu
- Department of Medical Laboratory/Microbiology Unit, ALERT Hospital, Addis Ababa, Ethiopia
| | - Setognal Birara
- Department of Epidemiology and Biostatics’, University of Gonder, Gonder, Ethiopia
| | - Chalachew Tiruneh
- Departments of Biomedical Science, Injibara University, Injibara, Ethiopia
| | - Abtie Abebaw
- Department of Medical Laboratory Science, Debere Markose University, Debere Markose, Ethiopia
| | - Yibeltal Akelew
- Department of Medical Laboratory Science, Debere Markose University, Debere Markose, Ethiopia
| | - Getu Abeje
- Departments of Biomedical Science, Samara University, Samara, Ethiopia
| | - Aklesya Enkobahry
- Departments of Biomedical Science, Injibara University, Injibara, Ethiopia
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Madrazo M, López-Cruz I, Piles L, Artero S, Alberola J, Aguilera JA, Eiros JM, Artero A. Risk Factors for Bacteremia and Its Clinical Impact on Complicated Community-Acquired Urinary Tract Infection. Microorganisms 2023; 11:1995. [PMID: 37630555 PMCID: PMC10459913 DOI: 10.3390/microorganisms11081995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/31/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Bacteremia has been associated with severity in some infections; however, its impact on the prognosis of urinary tract infections (UTIs) is still disputed. Our goal is to determine the risk factors for bacteremia and its clinical impact on hospitalized patients with complicated community-acquired urinary tract infections. We conducted a prospective observational study of patients admitted to the hospital with complicated community-acquired UTIs. Clinical variables and outcomes of patients with and without bacteremia were compared, and multivariate analysis was performed to identify risk factors for bacteremia and mortality. Of 279 patients with complicated community-acquired UTIs, 37.6% had positive blood cultures. Risk factors for bacteremia by multivariate analysis were temperature ≥ 38 °C (p = 0.006, OR 1.3 (95% CI 1.1-1.7)) and procalcitonin ≥ 0.5 ng/mL (p = 0.005, OR 8.5 (95% CI 2.2-39.4)). In-hospital and 30-day mortality were 9% and 13.6%, respectively. Quick SOFA (p = 0.030, OR 5.4 (95% CI 1.2-24.9)) and Barthel Index <40% (p = 0.020, OR 4.8 (95% CI 1.3-18.2)) were associated with 30-day mortality by multivariate analysis. However, bacteremia was not associated with 30-day mortality (p = 0.154, OR 2.7 (95% CI 0.7-10.3)). Our study found that febrile community-acquired UTIs and elevated procalcitonin were risk factors for bacteremia. The outcomes in patients with bacteremia were slightly worse, but without significant differences in mortality.
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Affiliation(s)
- Manuel Madrazo
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
| | - Ian López-Cruz
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
| | - Laura Piles
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
| | - Silvia Artero
- Gregorio Marañón University Hospital, 28007 Madrid, Spain;
| | - Juan Alberola
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
| | - Juan Alberto Aguilera
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
| | - José María Eiros
- Rio Hortega University Hospital, Universidad de Valladolid, 47012 Valladolid, Spain;
| | - Arturo Artero
- Doctor Peset University Hospital, University of Valencia, 46017 Valencia, Spain; (M.M.); (I.L.-C.); (L.P.); (J.A.A.); (A.A.)
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Haque Sumon AHMS, Al-Mahmood MR, Islam KA, Karim ANME, Aker P, Ullah A, Rashid MA, Hasan MN. Multidrug Resistance Urinary Tract Infection in Chronic Kidney Disease Patients: An Observational Study. Cureus 2023; 15:e38571. [PMID: 37284390 PMCID: PMC10239557 DOI: 10.7759/cureus.38571] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2023] [Indexed: 06/08/2023] Open
Abstract
OBJECTIVE To determine the presence of multidrug-resistant (MDR) urinary tract infections (UTI) and the MDR pattern of the bacterial isolates causing MDR UTI in chronic kidney disease (CKD) patients. METHODS This cross-sectional study was conducted among 326 diagnosed CKD patients in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University (BSMMU). Purposive sampling technique was used, and data were collected from the respondents using a semi-structured questionnaire. From duly collected urine samples, identification of organisms and antibiotic susceptibility tests were done, maintaining proper procedure in the microbiology laboratory. RESULTS The study population was predominantly female (60.1%). The outpatient department provided the majority of the respondents (75.2%). A history of UTI within the last six months was present among 74.2% of the respondents, and 59.2% had a history of taking antibiotics. Bacterial isolates were predominantly gram-negative (79.4%). Escherichia coli was the most prevalent bacterial isolate, present in 55.5% of the study population. Among the respondents, 64.7% were found to have MDR UTI, and among them, 81.5% were gram-negative, and 18.5% were gram-positive isolates. Among all the antibiotics tested, Colistin Sulphate, Polymyxin B, Cefoxitin, Vancomycin, and Linezolid had the highest (100%) sensitivity, followed by Meropenem, with 94.9% sensitivity. Among the gram-negative isolates, Acinetobacter and Enterobacter were most resistant to aminoglycoside, at 70% and 91.7%, respectively. E. coli, Klebsiella, Proteus, and Pseudomonas were most resistant to quinolone at 76.8%, 76.9%, 83.3%, and 66.7%, respectively. Among the gram-positive isolates, Enterococci and Staphylococcus aureus were most resistant to aminoglycoside, 81.5% and 88.9%, respectively. Streptococcus was found to be most resistant to cephalosporin (75.0%). There was a statistically significant (p < 0.05) relationship between MDR UTI, history of UTI, and previous antibiotic intake, and diabetic CKD. CONCLUSIONS The prevalence of MDR UTI among CKD patients is considerably high. When treating UTI, choosing an appropriate antibiotic by urine culture and implementing a guideline on the rational use of antibiotics are essential to managing and preventing the development of MDR UTI.
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Affiliation(s)
| | - Md Rashid Al-Mahmood
- Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
- Physical Medicine and Rehabilitation, Northern International Medical College, Dhaka, BGD
| | | | | | - Parvin Aker
- Biochemistry, Shaheed Ziaur Rahman Medical College Hospital, Bogura, BGD
| | - Ahsan Ullah
- Internal Medicine, Titas Upazila Health Complex, Cumilla, BGD
| | | | - Md Nazmul Hasan
- Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
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Development of a Method for the Fast Detection of Extended-Spectrum β-Lactamase- and Plasmid-Mediated AmpC β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae from Dogs and Cats in the USA. Animals (Basel) 2023; 13:ani13040649. [PMID: 36830436 PMCID: PMC9951654 DOI: 10.3390/ani13040649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/09/2023] [Accepted: 02/11/2023] [Indexed: 02/16/2023] Open
Abstract
Antibiotic resistance, such as resistance to beta-lactams and the development of resistance mechanisms, is associated with multifactorial phenomena and not only with the use of third-generation cephalosporins. Many methods have been recommended for the detection of ESBL and pAmpC β-lactamase production but they are very subjective and the appropriate facilities are not available in most laboratories, especially not in clinics. Therefore, for fast clinical antimicrobial selection, we need to rapidly detect ESBL- and pAmpC β-lactamase-producing bacteria using a simple method with samples containing large amounts of bacteria. For the detection of ESBL- and pAmpC phenotypes and genes, the disk diffusion test, DDST and multiplex PCR were conducted. Of the 109 samples, 99 (90.8%) samples were grown in MacConkey broth containing cephalothin, and 71 samples were grown on MacConkey agar containing ceftiofur. Of the 71 samples grown on MacConkey agar containing ceftiofur, 58 Escherichia coli and 19 Klebsiella pneumoniae isolates, in particular, harbored β-lactamase genes. Of the 38 samples that did not grow in MacConkey broth containing cephalothin or on MacConkey agar containing ceftiofur, 32 isolates were identified as E. coli, and 10 isolates were identified as K. pneumoniae; β-lactamase genes were not detected in these E. coli and K. pneumoniae isolates. Of the 78 ESBL- and pAmpC β-lactamase-producing E. coli and K. pneumoniae, 55 (70.5%) isolates carried one or more ESBL genes and 56 (71.8%) isolates carried one or more pAmpC β-lactamase genes. Our method is a fast, and low-cost tool for the screening of frequently encountered ESBL- and pAmpC β-lactamase-producing bacteria and it would assist in diagnosis and improve therapeutic treatment in animal hospitals.
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Fluoroquinolones Are Useful as Directed Treatment for Complicated UTI in a Setting with a High Prevalence of Quinolone-Resistant Microorganisms. Antibiotics (Basel) 2023; 12:antibiotics12010183. [PMID: 36671384 PMCID: PMC9854898 DOI: 10.3390/antibiotics12010183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 01/19/2023] Open
Abstract
Fluoroquinolones (FQs) have been widely used for treating urinary tract infections (UTIs); however, the increasing emergence of resistant strains has compromised their use. We aimed to know the usefulness of FQs for the treatment of community-acquired UTI in a setting with a high prevalence of fluoroquinolone-resistant microorganisms. A prospective observational study of patients diagnosed with community-acquired UTI was conducted, in which their outcomes according to whether they had FQs or not in their empirical and directed treatments were compared. A multivariate analysis was performed to identify risk factors for UTIs due to ciprofloxacin-resistant microorganisms. A total of 419 patients were included; 162 (38.7%) patients were treated with FQs, as empirical treatment in 27 (6.4%), and as directed treatment in 135 (32.2%). In-hospital mortality (2.2% vs. 6.6%, p 0.044) and 30-day mortality (4.4 vs. 11%, p 0.028) were both lower in the group of patients directly treated with FQ, while there were no differences when FQs were used as empirical treatment. A total of 37.2% of the cases were resistant to ciprofloxacin, which was associated with healthcare-associated UTI (OR 2.7, 95% CI 2-3.7) and prior exposure to FQs (OR 2.7, 95 % CI 1.9-3.7). In conclusion, our findings show that in a setting with a high prevalence of community-acquired UTI caused by quinolone-resistant microorganisms, FQs as directed treatment for community-acquired UTI were associated with better outcomes than other antibiotics, but their use as empirical treatment is not indicated, even in those cases without risk factors for quinolones resistance.
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11
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Kafi H, Emaneini M, Halimi S, Rahdar HA, Jabalameli F, Beigverdi R. Multiplex high-resolution melting assay for simultaneous detection of five key bacterial pathogens in urinary tract infections: A pilot study. Front Microbiol 2022; 13:1049178. [PMID: 36590389 PMCID: PMC9797728 DOI: 10.3389/fmicb.2022.1049178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022] Open
Abstract
The diagnosis of urinary tract infections (UTIs) is usually based on the results of urine culture, but it is time-consuming, labor-intensive and has a low sensitivity. The aim of this study was to develop multiplex high-resolution melting assay (MHRM) for the simultaneous detection of five common bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus, Enterococcus faecalis, and group B streptococci (GBS)) directly from urine samples. A total of 287 urine specimens were evaluated by HRM assay and the results were compared with the conventional culture method. Five different melt curves generated and differentiated five bacterial pathogens. The detection limit of the MHRM assay was 1.5 × 103 CFU/ml for E. coli and K. pneumoniae and 1.5 × 102 CFU/ml for S. saprophyticus, E. faecalis and GBS. Compared to culture, the specificity of the MHRM assay ranged from 99.3 to 100%, and sensitivity 100% for all test pathogens. The MHRM assay developed in the current study might be functional tool for the diagnosis of UTIs and has the potential for direct detection of the organism in the clinical samples. Additionally, it creates results in less than 5 h, helping clinicians to start treatment with appropriate antimicrobial agents. This method could be a useful supplement to urine culture.
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Affiliation(s)
- Hossein Kafi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Emaneini
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Ali Rahdar
- Department of Microbiology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Fereshteh Jabalameli
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Beigverdi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, Iran,*Correspondence: Reza Beigverdi,
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12
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A Meta-Analysis on Clinical Outcomes of Ceftolozane versus Piperacillin in Combination with Tazobactam in Patients with Complicated Urinary Tract Infections. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1639114. [PMID: 35978637 PMCID: PMC9377909 DOI: 10.1155/2022/1639114] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 02/18/2022] [Accepted: 05/12/2022] [Indexed: 11/22/2022]
Abstract
Objective To evaluate efficacy and adverse events of ceftolozane/tazobactam in complicated UTI including acute pyelonephritis. Method Databases that include PubMed, Embase, Scopus, and TRIP were searched. All randomized controlled trials and cohort studies were considered for the study. Statistical analysis was done using a fixed effects model, and results were expressed in proportion for dichotomous data and risk ratio for continuous data with 95% confidence intervals (CI). Results A clinical cure of ceftolozane/tazobactam was found to be 92% with 95% CI of 90-94 while that of piperacillin/tazobactam was only 78% (95% CI, 74-82) in patients with complicated UTI. Microbiological eradication was still higher in the ceftolozane/tazobactam group (83%, 95% CI 81-88) when compared with piperacillin/tazobactam (63% 95% CI, 58.77-65.2). Ceftolozane/tazobactam was more effective in the treatment of complicated urinary tract infections other than acute pyelonephritis as compared to piperacillin/tazobactam (RR = 1.21, 95% CI, 1.07-1.23). Serious adverse events were found comparable in both groups (RR = 1.15, 95% CI, 0.64-2.09). Conclusion The analysis showed that ceftolozane/tazobactam has better clinical outcomes including cure rates and low resistance for the treatment of complicated urinary tract infection.
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Chakrabarty S, Mishra MP, Bhattacharyay D. Targeting Microbial Bio-film: an Update on MDR Gram-Negative Bio-film Producers Causing Catheter-Associated Urinary Tract Infections. Appl Biochem Biotechnol 2022; 194:2796-2830. [PMID: 35247153 DOI: 10.1007/s12010-021-03711-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/08/2021] [Indexed: 11/26/2022]
Abstract
In every age group, urinary tract infection (UTI) is found as a major recurrence infectious disorder. Bio-films produced by bacteria perform a vital role in causing infection in the tract of the urinary system, leading to recurrences and relapses. The purpose of this review is to present the role and mechanism of bio-film producing MDR Gram-negative bacteria causing UTI, their significance, additionally the challenges for remedy and prevention of catheter-associated UTI. This work appreciates a new understanding of bio-film producers which are having multi-drug resistance capability and focuses on the effect and control of bio-film producing uropathogenic bacteria related to catheterization. We have tried to analyze approaches to target bio-film and reported phytochemicals with anti-bio-film activity also updated on anti-bio-film therapy.
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Affiliation(s)
- Susmita Chakrabarty
- School of Paramedics and Allied Health Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India
| | - Monali P Mishra
- School of Paramedics and Allied Health Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India.
| | - Dipankar Bhattacharyay
- School of Applied Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India
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Walusansa A, Asiimwe S, Nakavuma JL, Ssenku JE, Katuura E, Kafeero HM, Aruhomukama D, Nabatanzi A, Anywar G, Tugume AK, Kakudidi EK. Antibiotic-resistance in medically important bacteria isolated from commercial herbal medicines in Africa from 2000 to 2021: a systematic review and meta-analysis. Antimicrob Resist Infect Control 2022; 11:11. [PMID: 35063036 PMCID: PMC8781441 DOI: 10.1186/s13756-022-01054-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 01/05/2022] [Indexed: 01/10/2023] Open
Abstract
Background Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this continent, bacterial contamination of commonly used herbal medicine (HM) is on the increase, but information about antimicrobial resistance in these contaminants is limited due to fragmented studies. Here, we analyzed research that characterized ABR in pathogenic bacteria isolated from HM in Africa since 2000; to generate a comprehensive understanding of the drug-resistant bacterial contamination burden in this region. Methods The study was conducted according to standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We searched for articles from 12 databases. These were: PubMed, Science Direct, Scifinder scholar, Google scholar, HerbMed, Medline, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Commonwealth Agricultural Bureau Abstracts, African Journal Online, and Biological Abstracts. Prevalence and ABR traits of bacterial isolates, Cochran’s Q test, and the I2 statistic for heterogeneity were evaluated using MedCalcs software. A random-effects model was used to determine the pooled prevalence of ABR traits. The potential sources of heterogeneity were examined through sensitivity analysis, subgroup analysis, and meta-regression at a 95% level of significance. Findings Eighteen studies met our inclusion criteria. The pooled prevalence of bacterial resistance to at least one conventional drug was 86.51% (95% CI = 61.247–99.357%). The studies were highly heterogeneous (I2 = 99.17%; p < 0.0001), with no evidence of publication bias. The most prevalent multidrug-resistant species was Escherichia coli (24.0%). The most highly resisted drug was Ceftazidime with a pooled prevalence of 95.10% (95% CI = 78.51–99.87%), while the drug-class was 3rd generation cephalosporins; 91.64% (95% CI = 78.64–96.73%). None of the eligible studies tested isolates for Carbapenem resistance. Extended Spectrum β-lactamase genes were detected in 89 (37.2%) isolates, mostly Salmonella spp., Proteus vulgaris, and K. pneumonia. Resistance plasmids were found in 6 (5.8%) isolates; the heaviest plasmid weighed 23,130 Kilobases, and Proteus vulgaris harbored the majority (n = 5; 83.3%). Conclusions Herbal medicines in Africa harbor bacterial contaminants which are highly resistant to conventional medicines. This points to a potential treatment failure when these contaminants are involved in diseases causation. More research on this subject is recommended, to fill the evidence gaps and support the formation of collaborative quality control mechanisms for the herbal medicine industry in Africa.
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Affiliation(s)
- Abdul Walusansa
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda. .,Department of Medical Microbiology, Faculty of Health Sciences, Islamic University in Uganda, P. O. Box 2555, Kampala, Uganda. .,Department of Medical Microbiology and Immunology, Faculty of Health Sciences, Busitema University, Mbale, Uganda.
| | - Savina Asiimwe
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Jesca L Nakavuma
- College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O. Box 7062, Kampala, Uganda
| | - Jamilu E Ssenku
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Esther Katuura
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Hussein M Kafeero
- Department of Medical Microbiology, Faculty of Health Sciences, Islamic University in Uganda, P. O. Box 2555, Kampala, Uganda
| | - Dickson Aruhomukama
- Department of Immunology and Molecular Biology, Faculty of Health Sciences, Makerere University, Kampala, Uganda
| | - Alice Nabatanzi
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Godwin Anywar
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Arthur K Tugume
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
| | - Esezah K Kakudidi
- Department of Plant Sciences, Microbiology and Biotechnology, School of Biosciences, Makerere University, Kampala, Uganda
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Brem J, Panduwawala T, Hansen JU, Hewitt J, Liepins E, Donets P, Espina L, Farley AJM, Shubin K, Campillos GG, Kiuru P, Shishodia S, Krahn D, Leśniak RK, Schmidt Adrian J, Calvopiña K, Turrientes MC, Kavanagh ME, Lubriks D, Hinchliffe P, Langley GW, Aboklaish AF, Eneroth A, Backlund M, Baran AG, Nielsen EI, Speake M, Kuka J, Robinson J, Grinberga S, Robinson L, McDonough MA, Rydzik AM, Leissing TM, Jimenez-Castellanos JC, Avison MB, Da Silva Pinto S, Pannifer AD, Martjuga M, Widlake E, Priede M, Hopkins Navratilova I, Gniadkowski M, Belfrage AK, Brandt P, Yli-Kauhaluoma J, Bacque E, Page MGP, Björkling F, Tyrrell JM, Spencer J, Lang PA, Baranczewski P, Cantón R, McElroy SP, Jones PS, Baquero F, Suna E, Morrison A, Walsh TR, Schofield CJ. Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors. Nat Chem 2022; 14:15-24. [PMID: 34903857 DOI: 10.1038/s41557-021-00831-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 09/30/2021] [Indexed: 11/08/2022]
Abstract
Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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Affiliation(s)
- Jürgen Brem
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
| | - Tharindi Panduwawala
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | | | - Joanne Hewitt
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
| | | | - Pawel Donets
- Latvian Institute of Organic Synthesis, Riga, Latvia
| | - Laura Espina
- Department of Medical Microbiology, Institute of infection & Immunity, Cardiff University, Cardiff, UK
| | - Alistair J M Farley
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Kirill Shubin
- Latvian Institute of Organic Synthesis, Riga, Latvia
| | - Gonzalo Gomez Campillos
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Paula Kiuru
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
| | - Shifali Shishodia
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Daniel Krahn
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Robert K Leśniak
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Juliane Schmidt Adrian
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Karina Calvopiña
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - María-Carmen Turrientes
- Department of Microbiology, Ramón y Cajal University Hospital and Ramón y Cajal Institute for Health Research (IRYCIS), Madrid, Spain
| | - Madeline E Kavanagh
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
- Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA
| | | | - Philip Hinchliffe
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Gareth W Langley
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
- Charles River Laboratories, Saffron Walden, UK
| | - Ali F Aboklaish
- Department of Medical Microbiology, Institute of infection & Immunity, Cardiff University, Cardiff, UK
| | - Anders Eneroth
- Department of Pharmacy, Uppsala Drug Optimization and Pharmaceutical Profiling Platform (UDOPP), Uppsala University, Uppsala, Sweden
| | - Maria Backlund
- Department of Pharmacy, Uppsala Drug Optimization and Pharmaceutical Profiling Platform (UDOPP), Uppsala University, Uppsala, Sweden
| | | | | | - Michael Speake
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | - Janis Kuka
- Latvian Institute of Organic Synthesis, Riga, Latvia
| | - John Robinson
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | | | - Lindsay Robinson
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | - Michael A McDonough
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Anna M Rydzik
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
- Research and Early Development, Respiratory & Immunology, AstraZeneca, Mölndal, Sweden
| | - Thomas M Leissing
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Juan Carlos Jimenez-Castellanos
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
- Chemical Biology of Antibiotics, Centre for Infection & Immunity (CIIL), Pasteur Institute, INSERM U1019 - CNRS UMR 9017, Lille, France
| | - Matthew B Avison
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Solange Da Silva Pinto
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Andrew D Pannifer
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
| | | | - Emma Widlake
- Department of Medical Microbiology, Institute of infection & Immunity, Cardiff University, Cardiff, UK
| | | | | | - Marek Gniadkowski
- Department of Molecular Microbiology, National Medicines Institute, Warsaw, Poland
| | - Anna Karin Belfrage
- Department of Medicinal Chemistry, Drug Design and Discovery, Uppsala University, Uppsala, Sweden
| | - Peter Brandt
- Department of Medicinal Chemistry, Drug Design and Discovery, Uppsala University, Uppsala, Sweden
- Beactica Therapeutics AB, Uppsala, Sweden
| | - Jari Yli-Kauhaluoma
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
| | - Eric Bacque
- Evotec Infectious Diseases Lyon, Marcy l'Etoile, France
| | | | - Fredrik Björkling
- Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Jonathan M Tyrrell
- Department of Medical Microbiology, Institute of infection & Immunity, Cardiff University, Cardiff, UK
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - James Spencer
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Pauline A Lang
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK
| | - Pawel Baranczewski
- Department of Pharmacy, SciLifeLab Drug Discovery and Development Platform, ADME of Therapeutics Facility, Uppsala University, Uppsala, Sweden
| | - Rafael Cantón
- Department of Microbiology, Ramón y Cajal University Hospital and Ramón y Cajal Institute for Health Research (IRYCIS), Madrid, Spain
| | - Stuart P McElroy
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | - Philip S Jones
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | - Fernando Baquero
- Department of Microbiology, Ramón y Cajal University Hospital and Ramón y Cajal Institute for Health Research (IRYCIS), Madrid, Spain
| | - Edgars Suna
- Latvian Institute of Organic Synthesis, Riga, Latvia
| | - Angus Morrison
- University of Dundee, European Screening Centre, BioCity Scotland, Newhouse, UK
- BioAscent Discovery Ltd, Newhouse, UK
| | - Timothy R Walsh
- Department of Medical Microbiology, Institute of infection & Immunity, Cardiff University, Cardiff, UK
| | - Christopher J Schofield
- Department of Chemistry, Chemistry Research Laboratory and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
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Bassetti M, Garau J. Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections. J Antimicrob Chemother 2021; 76:iv23-iv37. [PMID: 34849997 PMCID: PMC8632738 DOI: 10.1093/jac/dkab352] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Microbial resistance is a serious threat to human health worldwide. Among the World Health Organisation's list of priority resistant bacteria, three are listed as critical-the highest level of concern-and all three are Gram-negative. Gram-negative resistance has spread worldwide via a variety of mechanisms, the most problematic being via AmpC enzymes, extended-spectrum β-lactamases, and carbapenemases. A combination of older drugs, many with high levels of toxicity, and newer agents are being used to combat multidrug resistance, with varying degrees of success. This review discusses the current treatments for multidrug-resistant Gram-negative bacteria, including new agents, older compounds, and new combinations of both, and some new treatment targets that are currently under investigation.
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Affiliation(s)
- Matteo Bassetti
- Clinica Malattie Infettive, Ospedale Policlinico San Martino—IRCCS, Genoa, Italy
- Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Javier Garau
- Hospital Universitari Mutua de Terrassa, Barcelona, Spain
- Clínica Rotger Quironsalud, Palma de Mallorca, Spain
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OXA-48 Carbapenemase-Encoding Transferable Plasmids of Klebsiella pneumoniae Recovered from Egyptian Patients Suffering from Complicated Urinary Tract Infections. BIOLOGY 2021; 10:biology10090889. [PMID: 34571766 PMCID: PMC8469419 DOI: 10.3390/biology10090889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/04/2021] [Accepted: 09/07/2021] [Indexed: 01/01/2023]
Abstract
Gram-negative bacteria are common causes of urinary tract infections (UTIs). Such pathogens can acquire genes encoding multiple mechanisms of antimicrobial resistance, including carbapenem resistance. The aim of this study was to detect the carbapenemase-producing ability of some Gram-negative bacterial isolates from urine specimens of patients suffering from complicated UTIs at two vital tertiary care hospitals in Cairo, Egypt; to determine the prevalence of carbapenemase genes among plasmid-bearing isolates; and explore the possibility of horizontal gene transfer to other bacterial species. The collected isolates were subjected to antimicrobial susceptibility testing, phenotypic analysis of carbapenemase production, and molecular detection of plasmid-borne carbapenemase genes, then the extracted plasmids were transformed into competent E. coli DH5α. A total of 256 Gram-negative bacterial clinical isolates were collected, 65 (25.4%) isolates showed carbapenem resistance of which 36 (55.4%) were carbapenemase-producers, and of these 31 (47.7%) harbored plasmids. The extracted plasmids were used as templates for PCR amplification of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP carbapenemase genes. The blaOXA-48 gene was detected in 24 (77.4%) of the tested isolates while blaVIM gene was detected in 8 (25.8%), both blaKPC and blaNDM genes were co-present in 1 (3.2%) isolate. Plasmids carrying the blaOXA-48 gene from 4 K. pneumoniae clinical isolates were successfully transformed into competent E. coli DH5α. The transformants were carbapenemase-producers and acquired resistance to some of the tested antimicrobial agents as compared to untransformed E. coli DH5α. The study concluded that the rate of carbapenem resistance among Gram-negative bacterial uropathogens in Cairo, Egypt is relatively high and can be transferred horizontally to other bacterial host(s).
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Mothibi LM, Bosman NN, Nana T. Fosfomycin susceptibility of uropathogens at Charlotte Maxeke Johannesburg Academic Hospital. S Afr J Infect Dis 2021; 35:173. [PMID: 34485478 PMCID: PMC8377994 DOI: 10.4102/sajid.v35i1.173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 08/13/2020] [Indexed: 01/09/2023] Open
Abstract
Background Multidrug-resistant uropathogens are becoming widespread both in community and hospital setting. Safe yet effective treatments are a priority. Fosfomycin is an antibacterial that displays good activity against most bacteria causing urinary tract infections (UTIs), including multidrug-resistant bacteria. The aim of this study was to evaluate fosfomycin susceptibility for uropathogens isolated from a microbiology laboratory at a tertiary academic hospital. In addition, this was compared to the susceptibility of other oral antimicrobials. Methods We conducted a retrospective analysis of laboratory reports for uropathogens isolated at Charlotte Maxeke Johannesburg Academic Hospital from September 2015 to August 2017. Antimicrobial susceptibility testing of the isolates was performed using the Kirby–Bauer disk diffusion method or the Vitek® 2 system according to the Clinical and Laboratory Standards Institute. Results Overall susceptibility of fosfomycin for the 4700 Enterobacteriaceae isolates was 95.7%; 95% confidence interval (CI) 95.1–96.2. The overall susceptibility for fosfomycin against the gram-positives was 98.6%. There were 37.9% multidrug-resistant Enterobacteriaceae (MDRE) isolated during the study period. Fosfomycin displayed activity against 94.4% of extended-spectrum β-lactamase (ESBL) producers and 90.7% for carbapenem-resistant Enterobacteriaceae (CRE). None of the methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus isolates tested was fosfomycin resistant. The overall in vitro susceptibility was significantly higher for fosfomycin (p = 0.0001) compared to amoxicillin/clavulanic acid, cephalexin, cefuroxime, ciprofloxacin, trimethoprim/sulfamethoxazole and nitrofurantoin. Conclusion This study confirmed the high susceptibility of fosfomycin against UTI pathogens isolated at our institution. In an era of increasing antimicrobial resistance, fosfomycin represents a potential option for the treatment of UTIs at Charlotte Maxeke Johannesburg Academic Hospital.
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Affiliation(s)
- Lesego M Mothibi
- Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Witwatersrand, Parktown, South Africa.,National Health Laboratory Services, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Norma N Bosman
- Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Witwatersrand, Parktown, South Africa.,National Health Laboratory Services, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
| | - Trusha Nana
- Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Witwatersrand, Parktown, South Africa.,National Health Laboratory Services, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
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Dobrindt U, Wami HT, Schmidt-Wieland T, Bertsch D, Oberdorfer K, Hof H. Compared with Cotrimoxazole Nitroxoline Seems to Be a Better Option for the Treatment and Prophylaxis of Urinary Tract Infections Caused by Multidrug-Resistant Uropathogens: An In Vitro Study. Antibiotics (Basel) 2021; 10:645. [PMID: 34071539 PMCID: PMC8230139 DOI: 10.3390/antibiotics10060645] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/17/2023] Open
Abstract
The resistance of uropathogens to various antibiotics is increasing, but nitroxoline remains active in vitro against some relevant multidrug resistant uropathogenic bacteria. E. coli strains, which are among the most common uropathogens, are unanimously susceptible. Thus, nitroxoline is an option for the therapy of urinary tract infections caused by multiresistant bacteria. Since nitroxoline is active against bacteria in biofilms, it will also be effective in patients with indwelling catheters or foreign bodies in the urinary tract. Cotrimoxazole, on the other hand, which, in principle, can also act on bacteria in biofilms, is frequently inactive against multiresistant uropathogens. Based on phenotypic resistance data from a large number of urine isolates, structural characterisation of an MDR plasmid of a recent ST131 uropathogenic E. coli isolate, and publicly available genomic data of resistant enterobacteria, we show that nitroxoline could be used instead of cotrimoxazole for intervention against MDR uropathogens. Particularly in uropathogenic E. coli, but also in other enterobacterial uropathogens, the frequent parallel resistance to different antibiotics due to the accumulation of multiple antibiotic resistance determinants on mobile genetic elements argues for greater consideration of nitroxoline in the treatment of uncomplicated urinary tract infections.
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Affiliation(s)
- Ulrich Dobrindt
- Institut für Hygiene, Universitätsklinikum Münster, 48149 Münster, Germany;
| | - Haleluya T. Wami
- Institut für Hygiene, Universitätsklinikum Münster, 48149 Münster, Germany;
| | - Torsten Schmidt-Wieland
- MVZ Labor Limbach und Kollegen, Im Breitspiel 16, 69126 Heidelberg, Germany; (T.S.-W.); (D.B.); (K.O.); (H.H.)
| | - Daniela Bertsch
- MVZ Labor Limbach und Kollegen, Im Breitspiel 16, 69126 Heidelberg, Germany; (T.S.-W.); (D.B.); (K.O.); (H.H.)
| | - Klaus Oberdorfer
- MVZ Labor Limbach und Kollegen, Im Breitspiel 16, 69126 Heidelberg, Germany; (T.S.-W.); (D.B.); (K.O.); (H.H.)
| | - Herbert Hof
- MVZ Labor Limbach und Kollegen, Im Breitspiel 16, 69126 Heidelberg, Germany; (T.S.-W.); (D.B.); (K.O.); (H.H.)
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Behzadi P, Urbán E, Matuz M, Benkő R, Gajdács M. The Role of Gram-Negative Bacteria in Urinary Tract Infections: Current Concepts and Therapeutic Options. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:35-69. [PMID: 32596751 DOI: 10.1007/5584_2020_566] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Urinary tract infections (UTIs) are some of the most common infections in human medicine worldwide, recognized as an important public health concern to healthcare systems around the globe. In addition, urine specimens are one of the most frequently submitted samples for culture to the clinical microbiology laboratory, exceeding the number of most of the other sample types. The epidemiology, species-distribution and susceptibility-patterns of uropathogens vary greatly in a geographical and time-dependent manner and it also strongly correlated with the reported patient population studied. Nevertheless, many studies highlight the fact that the etiological agents in UTIs have changed considerably, both in nosocomial and community settings, with a shift towards "less common" microorganisms having more pronounced roles. There is increasing demand for further research to advance diagnostics and treatment options, and to improve care of the patients. The aim of this review paper was to summarize current developments in the global burden of UTI, the diagnostic aspects of these infectious pathologies, the possible etiological agents and their virulence determinants (with a special focus on the members of the Enterobacterales order), current guidelines and quality indicators in the therapy of UTIs and the emergence of multidrug resistance in urinary pathogens.
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Affiliation(s)
- Payam Behzadi
- Department of Microbiology, College of Basic Sciences Islamic Azad University, Tehran, Iran
| | - Edit Urbán
- Department of Public Health, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Institute of Translational Medicine, University of Pécs, Medical School, Pécs, Hungary
| | - Mária Matuz
- Department of Clinical Pharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
| | - Ria Benkő
- Department of Clinical Pharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
- Central Pharmacy Service, Emergency Department, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Márió Gajdács
- Institute of Medical Microbiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
- Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
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Veeraraghavan B, Bakthavatchalam YD, Sahni RD. Orally Administered Amoxicillin/Clavulanate: Current Role in Outpatient Therapy. Infect Dis Ther 2020; 10:15-25. [PMID: 33306184 PMCID: PMC7954971 DOI: 10.1007/s40121-020-00374-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 11/19/2020] [Indexed: 02/04/2023] Open
Abstract
Oral amoxicillin/clavulanate is a community workhorse antibiotic, routinely prescribed for respiratory tract infections, skin infections as well as urinary tract infections (UTIs). Multiple adult and paediatric dose formulations of amoxicillin/clavulanate are available in different parts of the world. In adult formulations, clavulanic acid dose is restricted to 125 mg because of tolerability issues. Despite its popular use for 40 years, few pharmacokinetic/pharmacodynamic (PK/PD) studies were undertaken to justify the doses and breakpoints currently in use for various infections. Clavulanate has a minimal role in the combination’s use for respiratory infections. In the context of rising extended spectrum beta-lactamase (ESBL) prevalence globally, empirical and overuse of orally administered amoxicillin/clavulanate may select resistance in Gram-negative pathogens. The susceptibility test methods and interpretive criteria differ between the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Third-generation oral cephalosporins such as ceftibuten or cefpodoxime can be combined with amoxicillin/clavulanate to tackle UTIs involving ESBL producing Escherichia coli and Klebsiella spp. Clinicians who routinely prescribe amoxicillin/clavulanate in outpatient settings should be aware of potential benefits and limitations of this combination.
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Affiliation(s)
| | | | - Rani Diana Sahni
- Department of Clinical Microbiology, Christian Medical College, Vellore, India
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Clinico-Microbiological Investigation on Fosfomycin and Tigecycline Resistant Gram-Negative Bacilli Isolated from Urinary Tract Infections: A Potential Resurgence. Jundishapur J Microbiol 2020. [DOI: 10.5812/jjm.99990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Traditional antibiotics are no longer as effective as before for controlling pathogens associated with urinary tract infections (UTI), which shows the necessity of developing new and more effective antibiotics. Objectives: The current study aimed to evaluate in vitro susceptibility of fosfomycin and tigecycline towards common antibiotic-resistant Gram-negative bacilli isolated from the urinary tract. Besides, clinico-microbiological on fosfomycin and tigecycline resistant Gram-negative bacilli was investigated. Methods: In this descriptive cross-sectional study, 150 resistant Gram-negative bacilli were isolated from urine specimens send for culture, and antibiotic susceptibility assessment to the Division of Microbiology of Sina Hospital affiliated to Tabriz University of Medical Sciences which were collected from April-September 2017 are included. Antibiotic susceptibilities were evaluated according to the Clinical and Laboratory Standards published by the Institute and the criteria of the Food and Drug Administration. Results: Of 150 isolates, 138 (92%) were susceptible, and 2 (1.3%) were resistant to both fosfomycin and tigecycline, as confirmed by disk diffusion and Epsilonmeter tests. The difference was statistically significant (P = 0.001). Conclusions: Based on the results, resistance to the conventional antibiotics prescribed for the treatment of UTI was significantly high. Fosfomycin and tigecycline have an appropriate antimicrobial activity towards Gram-negative-resistant isolates involved in UTIs.
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Tehrani S, Elyasi F, Abolghasemi S. Levofloxacin versus ceftriaxone for treatment of acute pyelonephritis in Iranian adults. Infect Disord Drug Targets 2020; 21:603-607. [PMID: 32720608 DOI: 10.2174/1871526520999200727154214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/01/2020] [Accepted: 07/06/2020] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Acute pyelonephritis is among the most common bacterial infections. Options for initial treatment of pyelonephritis include an extended-spectrum cephalosporin or a fluoroquinolone. In this study, we aimed to compare the clinical outcomes of patients receiving ceftriaxone to those who received levofloxacin for the treatment of acute pyelone-phritis. METHODS In this randomized, open-label trial, hospitalized adults with acute pyelonephritis were treated with ceftriaxone (1g IV every 12 hours) or levofloxacin (750 mg IV daily) for at least 7 days. Clinical and microbiological characteristics were compared among patients treated with ceftriaxone and levofloxacin. RESULTS A total of 59 patients were randomized, 30 to the ceftriaxone group and 29 to the levofloxacin group. The clinical response for 68.0% of patients in the ceftriaxone group and 56.0% of patients in the levofloxacin group were cured. The mi-crobiological response (pathogen eradication rates) was 68.7% in the ceftriaxone group and 21.4% in the levofloxacin group.(P value=0.00028) Escherichia coliwas the most common pathogen (n = 31), followed by Klebsiella pneumoniae(n = 21). High resistance rates were detected for cotrimoxazole (55%), ciprofloxacin (48%), and ceftriaxone (34.4%) in isolat-ed E.coli. Likewise, all K. pneumoniaeisolates were resistant to ciprofloxacin. CONCLUSIONS Our study indicates that ceftriaxone was more effective than levofloxacin in the treatment of acute pyelone-phritis, on the basis of microbiological response, but there were no statistically significant differences between the treatment groups in the rates of clinical cure.The resistance of uropathogens to the most used antibiotics was relatively high. Choosing the treatment regimen based on susceptibility testing results and shortening the duration of the therapy are now recommend-ed to be the most important approaches to decrease the spread of antibiotic resistance worldwide.
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Affiliation(s)
- Shabnam Tehrani
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Fereshteh Elyasi
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
| | - Sara Abolghasemi
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran. Iran
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24
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Reza A, Sutton JM, Rahman KM. Effectiveness of Efflux Pump Inhibitors as Biofilm Disruptors and Resistance Breakers in Gram-Negative (ESKAPEE) Bacteria. Antibiotics (Basel) 2019; 8:antibiotics8040229. [PMID: 31752382 PMCID: PMC6963839 DOI: 10.3390/antibiotics8040229] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/07/2019] [Accepted: 11/12/2019] [Indexed: 12/21/2022] Open
Abstract
Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli), in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.
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Affiliation(s)
- Akif Reza
- Institute of Pharmaceutical Science, King’s College London, London, SE1 9NH, UK;
| | - J. Mark Sutton
- National Infections Service, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK;
| | - Khondaker Miraz Rahman
- Institute of Pharmaceutical Science, King’s College London, London, SE1 9NH, UK;
- Correspondence: ; Tel.: +44-(0)207-848-1891
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25
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Morris BJ, Moreton S, Krieger JN. Critical evaluation of arguments opposing male circumcision: A systematic review. J Evid Based Med 2019; 12:263-290. [PMID: 31496128 PMCID: PMC6899915 DOI: 10.1111/jebm.12361] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/03/2019] [Accepted: 05/12/2019] [Indexed: 12/22/2022]
Abstract
OBJECTIVE To systematically evaluate evidence against male circumcision (MC). METHODS We searched PubMed, Google Scholar, EMBASE and Cochrane databases. RESULTS Database searches retrieved 297 publications for inclusion. Bibliographies of these yielded 101 more. After evaluation we found: Claims that MC carries high risk were contradicted by low frequency of adverse events that were virtually all minor and easily treated with complete resolution. Claims that MC causes psychological harm were contradicted by studies finding no such harm. Claims that MC impairs sexual function and pleasure were contradicted by high-quality studies finding no adverse effect. Claims disputing the medical benefits of MC were contradicted by a large body of high-quality evidence indicating protection against a wide range of infections, dermatological conditions, and genital cancers in males and the female sexual partners of men. Risk-benefit analyses reported that benefits exceed risks by 100-200 to 1. To maximize benefits and minimize risks, the evidence supported early infant MC rather than arguments that the procedure should be delayed until males are old enough to decide for themselves. Claims that MC of minors is unethical were contradicted by balanced evaluations of ethical issues supporting the rights of children to be provided with low-risk, high-benefit interventions such as MC for better health. Expert evaluations of case-law supported the legality of MC of minors. Other data demonstrated that early infant MC is cost-saving to health systems. CONCLUSIONS Arguments opposing MC are supported mostly by low-quality evidence and opinion, and are contradicted by strong scientific evidence.
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Affiliation(s)
- Brian J Morris
- School of Medical SciencesUniversity of SydneySydneyNew South WalesAustralia
| | | | - John N Krieger
- Department of UrologyUniversity of Washington School of MedicineSeattleWashington
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Shruti SR, Rajasekaran R. Identification of therapeutic peptide scaffold from tritrpticin family for urinary tract infections using in silico techniques. J Biomol Struct Dyn 2019; 38:4407-4417. [DOI: 10.1080/07391102.2019.1680437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- S. R. Shruti
- Department of Biotechnology, School of Biosciences and Technology, VIT (Deemed to Be University), Vellore, India
| | - R. Rajasekaran
- Department of Biotechnology, School of Biosciences and Technology, VIT (Deemed to Be University), Vellore, India
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Smith JS, Borts DJ, Slagel CC, Rajewski SM, Bousquet-Melou A, Ferran AA, Plummer PJ, Mochel JP. Pharmacokinetics of Ertapenem in Sheep ( Ovis aries) with Experimentally Induced Urinary Tract Infection. Comp Med 2019; 69:413-418. [PMID: 31581974 DOI: 10.30802/aalas-cm-18-000144] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Sheep are commonly used as animal models for human biomedical research, but descriptions of their use for studying the pharmacokinetics of carbapenem antimicrobials, such as ertapenem, are unavailable. Ertapenem is a critical antimicrobial for human infections, and the description of the pharmacokinetics of this drug is of value for research using ovine as models for human diseases, such as urinary tract infections (UTI). There are currently no ovine models for comparative biomedical research of UTI. The objective of this study was to report the pharmacokinetics of ertapenem in sheep after single and multiple dosing. In addition, we explored the effects of an immunomodulatory drug (Zelnate) on the pharmacokinetics of ertapenem in sheep. Eight healthy ewes (weight, 64.4 ± 7.7 kg) were used in an ovine bacterial cystitis model of human cystitis with Pseudomonas aeruginosa. After disease confirmation, each ewe received 1 g of ertapenem intravenously once every 24 h for 5 administrations. Blood was collected intensively (14 samples) during 24 h after the first and last administration. After multiple-dose administration, the volume of distribution was 84.5 mL/kg, clearance was 116.3 mL/h/kg, T1/2(λz) was 1.1 h, and the extraction ratio was 0.02. No significant differences in pharmacokinetic parameters or time points were found between groups treated with the immunostimulant and controls or after the 1st or 5th administration of ertapenem. No accumulation was noted from previous administration. Our ovine pharmacokinetic findings can be used to evaluate therapeutic strategies for ertapenem use (varying drug dosing schedules and combinations with other antimicrobials or immune modulators) in the context of UTI.
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Affiliation(s)
- Joe S Smith
- Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa: Systems Modelling and Reverse Translational (SMART) Pharmacology, Iowa State University, Ames, Iowa;,
| | - David J Borts
- Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa
| | - Clare C Slagel
- Analytical Chemistry Services, Iowa State University, Ames, Iowa
| | | | | | - Aude A Ferran
- INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France
| | - Paul J Plummer
- Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa; Veterinary Microbiology and Preventative Medicine, Iowa State University, Ames, Iowa; National Institute of Antimicrobial Resistance Research and Education, Ames, Iowa
| | - Jon P Mochel
- Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa; Systems Modelling and Reverse Translational (SMART) Pharmacology, Iowa State University, Ames, Iowa
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Gajdács M, Ábrók M, Lázár A, Burián K. Comparative Epidemiology and Resistance Trends of Common Urinary Pathogens in a Tertiary-Care Hospital: A 10-Year Surveillance Study. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:356. [PMID: 31324035 PMCID: PMC6681214 DOI: 10.3390/medicina55070356] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/08/2019] [Accepted: 07/08/2019] [Indexed: 12/17/2022]
Abstract
Background and Objective: Urinary tract infections (UTIs) are common in human medicine, affecting large patient populations worldwide. The principal cause of UTIs is uropathogenic Escherichia coli (UPEC) and Klebsiella, both in community and nosocomial settings. The assessment of local data on prevalence and resistance is essential to evaluate trends over time and to reflect on the national situation, compared to international data, using the methods of analytical epidemiology. Materials and Methods: The aim of this study was to assess resistance trends and epidemiology of UTIs caused by E. coli and Klebsiella species in inpatients and outpatients at a tertiary-care hospital in Hungary, using microbiological data. To evaluate resistance trends, several antibiotics were chosen as indicator drugs, based on local utilization data. Results: E. coli was the most prevalent isolate, representing 56.75 ± 4.86% for outpatients and 42.29 ± 2.94% for inpatients. For E. coli, the ratio of resistant strains for several antibiotics was significantly higher in the inpatient group, while in Klebsiella, similar trends were only observed for gentamicin. Extended-spectrum β-lactamase (ESBL)-producing isolates were detected in 4.33-9.15% and 23.22-34.22% from outpatient, 8.85-38.97% and 10.89-36.06% from inpatient samples for E. coli and Klebsiella, respectively. Conclusions: Resistance developments in common UTI pathogens (especially to fosfomycin, sulfamethoxazole-trimethoprim, fluoroquinolones, and 3rd generation cephalosporins), seriously curb therapeutic options, especially in outpatient settings.
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Affiliation(s)
- Márió Gajdács
- Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös utca 6., 6720 Szeged, Hungary.
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary.
| | - Marianna Ábrók
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary
| | - Andrea Lázár
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary
| | - Katalin Burián
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary
- Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10., 6720 Szeged, Hungary
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Bielen L, Likic R. Experience with fosfomycin in the treatment of complicated urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Ther Adv Infect Dis 2019; 6:2049936119858883. [PMID: 31258896 PMCID: PMC6591653 DOI: 10.1177/2049936119858883] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 05/30/2019] [Indexed: 11/16/2022] Open
Abstract
Background The aim of this study was to evaluate the efficacy of fosfomycin in the treatment of complicated urinary tract infections (cUTIs) caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. Methods We retrospectively evaluated 42 ambulatory patients with cUTIs caused by ESBL-producing Enterobacteriaceae at the Outpatient Internal Medicine Clinic of the University Clinical Hospital Centre Zagreb in the period from June 2012 to June 2014. ESBL production was confirmed by double disk synergy test according to Jarlier. In vitro susceptibility to fosfomycin of ESBL-producing Escherichia coli, Klebsiella pneumoniae and Citrobacter freundii isolates was tested according to the European Committee on Antimicrobial Susceptibility Testing methodology. Results In 42 patients with cUTIs, 43 urinary pathogens susceptible to fosfomycin were isolated in the urine cultures, including 34 E. coli ESBL, seven K. pneumoniae ESBL and two C. freundii ESBL isolates. On average, patients had 2.2 complicating factors (CFs) and received 3.6 fosfomycin doses per treatment course. The overall microbiological cure was 50%, clinical cure was 71% and ESBL eradication rate was 74%. Patients with between zero and one CFs received significantly fewer fosfomycin doses than patients with two or more CFs (p = 0.022). Three kidney transplant patients achieved microbiological cure following prolonged fosfomycin administration. No statistically significant correlation was found between the presence of individual CFs and treatment outcome. Conclusions Fosfomycin may be a valid option for oral treatment of cUTIs caused by ESBL-producing pathogens. The optimal duration of fosfomycin treatment for cUTIs remains to be determined.
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Affiliation(s)
- Luka Bielen
- University Clinical Hospital Centre Zagreb, Croatia University of Zagreb School of Medicine, Croatia
| | - Robert Likic
- Department of Internal Medicine, Unit of Clinical Pharmacology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia
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In Vivo Pharmacodynamic Profile of Ceftibuten-Clavulanate Combination against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in the Murine Thigh Infection Model. Antimicrob Agents Chemother 2019; 63:AAC.00145-19. [PMID: 31061165 DOI: 10.1128/aac.00145-19] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/26/2019] [Indexed: 01/12/2023] Open
Abstract
Ceftibuten-clavulanate (CTB-CLA) is a novel β-lactam-β-lactamase combination with potential utility for the management of urinary tract infections caused by extended-spectrum-β-lactamase (ESBL)-producing organisms. We examined the pharmacodynamics of the combination against 25 Enterobacteriaceae expressing β-lactamases (CTX-M, TEM, and SHV wild types and SHV-ESBL) in the murine thigh infection model. MIC values of CTB and CTB-CLA ranged from 1 to >32 mg/liter and 0.125 to 8 mg/liter, respectively. Human-simulated regimens of CTB and CLA equivalent to clinical doses of 400 mg orally (p.o.) every 8 h (q8h) and 187 mg q8h, respectively, were developed. CLA dose fractionation studies were undertaken to characterize the driver of efficacy. CLA dose-ranging studies were undertaken to assess the activity of the CTB human-simulated regimen in combination with escalating CLA exposures. The relationships between the percentage of the dosing interval during which the free CLA plasma concentrations remained above a threshold concentration (%fT>CT ) and the change in log10 CFU per thigh at 24 h were examined across different threshold concentrations. Additionally, the efficacy of a human-simulated regimen of CTB-CLA was assessed against isolates with various susceptibilities to the combination. The pharmacokinetic/pharmacodynamic index that best correlated with the efficacy of the combination was %fT > threshold CLA plasma concentration of 0.5 mg/liter. The plasma %fT>0.5 mg/liter associated with the static endpoint was 20.59%. For isolates with CTB-CLA MICs of ≤4 mg/liter, stasis was achieved with a human-simulated regimen of CTB-CLA against 20/22 isolates (90.9%), while for isolates with MICs of 8 mg/liter, only 1/3 tested isolates (33.3%) displayed stasis. Results suggest a susceptibility breakpoint of 4 mg/liter for CTB-CLA. These data support the consideration of the CTB-CLA combination for the treatment of urinary tract infections due to ESBL-producing Enterobacteriaceae.
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Gajdács M, Urbán E. Resistance Trends and Epidemiology of Citrobacter- Enterobacter- Serratia in Urinary Tract Infections of Inpatients and Outpatients (RECESUTI): A 10-Year Survey. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E285. [PMID: 31216725 PMCID: PMC6630883 DOI: 10.3390/medicina55060285] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 06/12/2019] [Accepted: 06/13/2019] [Indexed: 12/17/2022]
Abstract
Background and objectives: Urinary tract infections (UTIs) are the third most common infections in humans, representing a significant factor of morbidity, both among outpatients and inpatients. The pathogenic role of Citrobacter, Enterobacter, and Serratia species (CES bacteria) has been described in UTIs. CES bacteria present a therapeutic challenge due to the various intrinsic and acquired resistance mechanisms they possess. Materials and Methods: The aim of this study was to assess and compare the resistance trends and epidemiology of CES pathogens in UTIs (RECESUTI) in inpatients and outpatients during a 10-year study period. To evaluate the resistance trends of isolated strains, several antibiotics were chosen as indicator drugs based on local utilization data. 578 CES isolates were obtained from inpatients and 554 from outpatients, representing 2.57 ± 0.41% of all positive urine samples for outpatients and 3.02 ± 0.40% for inpatients. E. cloacae was the most prevalent species. Results: The ratio of resistant strains to most of the indicator drugs was higher in the inpatient group and lower in the second half of the study period. ESBL-producing isolates were detected in 0-9.75% from outpatient and 0-29.09% from inpatient samples. Conclusions: Resistance developments of CES bacteria, coupled with their intrinsic non-susceptibility to several antibiotics, severely limits the number of therapeutic alternatives, especially for outpatients.
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Affiliation(s)
- Márió Gajdács
- Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös utca 6., 6720 Szeged, Hungary.
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary.
| | - Edit Urbán
- Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary.
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Zhao C, Wang X, Zhang Y, Wang R, Wang Q, Li H, Wang H. In vitro activities of Eravacycline against 336 isolates collected from 2012 to 2016 from 11 teaching hospitals in China. BMC Infect Dis 2019; 19:508. [PMID: 31182038 PMCID: PMC6558774 DOI: 10.1186/s12879-019-4093-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 05/15/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In China multidrug-resistant bacteria pose a considerable threat to public health. Antimicrobial resistance has weakened the effectiveness of many medicines widely used today. Thus, discovering new antibacterial drugs is paramount in the effort to treat emerging drug-resistant bacteria. METHODS Eravacycline, tigecycline and other clinical routine antibiotics were tested by reference broth micro-dilution method against 336 different strains collected from 11 teaching hospitals in China between 2012 and 2016. These isolates included Enterobacteriaceae, non-fermentative, Staphylococcus spp., Enterococcus, and a number of fastidious organisms. The strains involved in this study possess the most important drug resistance characteristics currently known in China. Drug resistant bacteria such as those producing extended spectrum β-lactamases (ESBL) and carbapenemases (KPC-2 and NDM-1), and those exhibiting colistin resistance (mcr-1) and tigecycline were included in this study. Additionally, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), β-lactamase positive Haemophilus influenzae, and penicillin resistant Streptococcus pneumoniae (PRSP) were also included. RESULTS Eravacycline exhibited good efficacy against all the strains tested, especially for organisms with ESBLs, carbapenemases, and mcr-1 gene compared with tigecycline and other antibiotics tested. The MIC values of eravacycline against carbapenemase producing Enterobacteriaceae and OXA-23-producing A. baumannii were much lower than the MIC values of other antibiotics. MRSA, VRE, β-lactamase positive Haemophilus influenza, and PRSP were sensitive to eravacycline in every strain tested. Furthermore, in most strains tested, the MICs of eravacycline were two to four-fold lower than the MICs of tigecycline. CONCLUSIONS Eravacycline has shown potent antibacterial activity against common and clinically important antibiotic-resistant pathogens. The MIC distribution of eravacycline was generally lower than that of tigecycline which demonstrates that this new drug is potentially more effective than the existing medications.
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Affiliation(s)
- Chunjiang Zhao
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Xiaojuan Wang
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Yawei Zhang
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Ruobing Wang
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Qi Wang
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Henan Li
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China
| | - Hui Wang
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China.
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Davis C. Catheter-associated urinary tract infection: signs, diagnosis, prevention. ACTA ACUST UNITED AC 2019; 28:96-100. [DOI: 10.12968/bjon.2019.28.2.96] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Cathy Davis
- Clinical Nurse Specialist in Urogynaecology, King's College Hospital, London
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Smieško G. Infection of urinary tract in menopausal women. SANAMED 2019. [DOI: 10.24125/sanamed.v14i2.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Urinary infections are, by frequency, in the second place, immediately behind respiratory infections. The prevalence of urinary tract infections is generally increasing. UTI (urinary tract infections) is more common in women and very young people. The rates of occurrence generally reflect predisposing factors such as congenital anomalies in childhood, the onset of sexual activity, especially in women, and, of course, postmenopausal changes in older women. It is assumed that 50-60% of women can expect an episode of urinary infection during their lifetime. In postmenopausal women, there is a deficit in estrogen. It is one of the important factors that indirectly protects the vaginal mucous membranes as well as the uroepitel from infection. Bacteria from the digestive tract colonize the skin of the perineum, then the vulva, the vagina and the outer opening of the urethra. Normal vaginal flora (lactobacilli) protects the vagina from colonization by fecal bacteria because it lowers pH and creates unfavorable conditions for survival of bacteria.
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Gomila A, Carratalà J, Eliakim-Raz N, Shaw E, Wiegand I, Vallejo-Torres L, Gorostiza A, Vigo JM, Morris S, Stoddart M, Grier S, Vank C, Cuperus N, Van den Heuvel L, Vuong C, MacGowan A, Leibovici L, Addy I, Pujol M. Risk factors and prognosis of complicated urinary tract infections caused by Pseudomonas aeruginosa in hospitalized patients: a retrospective multicenter cohort study. Infect Drug Resist 2018; 11:2571-2581. [PMID: 30588040 PMCID: PMC6302800 DOI: 10.2147/idr.s185753] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Purpose Complicated urinary tract infections (cUTIs) are among the most frequent health-care-associated infections. In patients with cUTI, Pseudomonas aeruginosa deserves special attention, since it can affect patients with serious underlying conditions. Our aim was to gain insight into the risk factors and prognosis of P. aeruginosa cUTIs in a scenario of increasing multidrug resistance (MDR). Methods This was a multinational, retrospective, observational study at 20 hospitals in south and southeastern Europe, Turkey, and Israel including consecutive patients with cUTI hospitalized between January 2013 and December 2014. A mixed-effect logistic regression model was performed to assess risk factors for P. aeruginosa and MDR P. aeruginosa cUTI. Results Of 1,007 episodes of cUTI, 97 (9.6%) were due to P. aeruginosa. Resistance rates of P. aeruginosa were: antipseudomonal cephalosporins 35 of 97 (36.1%), aminoglycosides 30 of 97 (30.9%), piperacillin-tazobactam 21 of 97 (21.6%), fluoroquinolones 43 of 97 (44.3%), and carbapenems 28 of 97 (28.8%). The MDR rate was 28 of 97 (28.8%). Independent risk factors for P. aeruginosa cUTI were male sex (OR 2.61, 95% CI 1.60-4.27), steroid therapy (OR 2.40, 95% CI 1.10-5.27), bedridden functional status (OR 1.79, 95% CI 0.99-3.25), antibiotic treatment within the previous 30 days (OR 2.34, 95% CI 1.38-3.94), indwelling urinary catheter (OR 2.41, 95% CI 1.43-4.08), and procedures that anatomically modified the urinary tract (OR 2.01, 95% CI 1.04-3.87). Independent risk factors for MDR P. aeruginosa cUTI were age (OR 0.96, 95% CI 0.93-0.99) and anatomical urinary tract modification (OR 4.75, 95% CI 1.06-21.26). Readmission was higher in P. aeruginosa cUTI patients than in other etiologies (23 of 97 [23.7%] vs 144 of 910 [15.8%], P=0.04), while 30-day mortality was not significantly different (seven of 97 [7.2%] vs 77 of 910 [8.5%], P=0.6). Conclusion Patients with P. aeruginosa cUTI had characteristically a serious baseline condition and manipulation of the urinary tract, although their mortality was not higher than that of patients with cUTI caused by other etiologies.
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Affiliation(s)
- Aina Gomila
- Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, .,Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain,
| | - J Carratalà
- Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, .,Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain, .,Infectious Diseases Department, University of Barcelona, Barcelona, Spain
| | - N Eliakim-Raz
- Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - E Shaw
- Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, .,Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain,
| | - I Wiegand
- AiCuris Anti-infective Cures, Wuppertal, Germany
| | - L Vallejo-Torres
- UCL Department of Applied Health Research, University College London, London, UK
| | - A Gorostiza
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain,
| | - J M Vigo
- Informatics Unit, Fundació Institut Català de Farmacologia, Barcelona, Spain
| | - S Morris
- UCL Department of Applied Health Research, University College London, London, UK
| | - M Stoddart
- Department of Medical Microbiology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - S Grier
- Department of Medical Microbiology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - C Vank
- AiCuris Anti-infective Cures, Wuppertal, Germany
| | - N Cuperus
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - L Van den Heuvel
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - C Vuong
- AiCuris Anti-infective Cures, Wuppertal, Germany
| | - A MacGowan
- Department of Medical Microbiology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - L Leibovici
- Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - I Addy
- AiCuris Anti-infective Cures, Wuppertal, Germany
| | - M Pujol
- Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, .,Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain,
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Nitroxoline: an option for the treatment of urinary tract infection with multi-resistant uropathogenic bacteria. Infection 2018; 47:493-495. [DOI: 10.1007/s15010-018-1253-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 11/13/2018] [Indexed: 10/27/2022]
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Hollenbeck EC, Antonoplis A, Chai C, Thongsomboon W, Fuller GG, Cegelski L. Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenic Escherichia coli to bladder epithelial cells. Proc Natl Acad Sci U S A 2018; 115:10106-10111. [PMID: 30232265 PMCID: PMC6176564 DOI: 10.1073/pnas.1801564115] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infections, employing numerous molecular strategies to contribute to adhesion, colonization, and persistence in the bladder niche. Identifying strategies to prevent adhesion and colonization is a promising approach to inhibit bacterial pathogenesis and to help preserve the efficacy of available antibiotics. This approach requires an improved understanding of the molecular determinants of adhesion to the bladder urothelium. We designed experiments using a custom-built live cell monolayer rheometer (LCMR) to quantitatively measure individual and combined contributions of bacterial cell surface structures [type 1 pili, curli, and phosphoethanolamine (pEtN) cellulose] to bladder cell adhesion. Using the UPEC strain UTI89, isogenic mutants, and controlled conditions for the differential production of cell surface structures, we discovered that curli can promote stronger adhesive interactions with bladder cells than type 1 pili. Moreover, the coproduction of curli and pEtN cellulose enhanced adhesion. The LCMR enables the evaluation of adhesion under high-shear conditions to reveal this role for pEtN cellulose which escaped detection using conventional tissue culture adhesion assays. Together with complementary biochemical experiments, the results support a model wherein cellulose serves a mortar-like function to promote curli association with and around the bacterial cell surface, resulting in increased bacterial adhesion strength at the bladder cell surface.
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Affiliation(s)
- Emily C Hollenbeck
- Department of Chemical Engineering, Stanford University, Stanford, CA 94305
| | | | - Chew Chai
- Department of Bioengineering, Stanford University, Stanford, CA 94305
| | | | - Gerald G Fuller
- Department of Chemical Engineering, Stanford University, Stanford, CA 94305;
| | - Lynette Cegelski
- Department of Chemistry, Stanford University, Stanford, CA 94305;
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Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections. Antimicrob Resist Infect Control 2018; 7:111. [PMID: 30220999 PMCID: PMC6137881 DOI: 10.1186/s13756-018-0401-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 08/29/2018] [Indexed: 12/03/2022] Open
Abstract
Background Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI. Methods This is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI. Results From 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20–2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80–3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99–2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28–2.79) and antibiotic treatment within the previous 30 days (OR, 1.68; 95%CI, 1.13–2.50). Conclusions The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance. Electronic supplementary material The online version of this article (10.1186/s13756-018-0401-6) contains supplementary material, which is available to authorized users.
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Faine BA, Mohr N, Vakkalanka P, Gao AS, Liang SY. Validation of a Clinical Decision Rule to Identify Risk Factors Associated With Multidrug-Resistant Urinary Pathogens in the Emergency Department. Ann Pharmacother 2018; 53:56-60. [PMID: 30066573 DOI: 10.1177/1060028018792680] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Antimicrobial resistance remains a significant obstacle for clinicians when treating patients presenting to the emergency department (ED) with urinary tract infections. OBJECTIVE The goal of the proposed study was to validate a previously developed clinical decision rule identifying risk factors for multidrug-resistant (MDR) urinary pathogens. METHODS We conducted a validation study of a previously published clinical decision rule to identify patients with MDR urinary pathogens using a cohort from an urban academic center ED with annual census over 80 000. Using our previously identified clinical risk factors, we determined the sensitivity, specificity, positive likelihood ratio (+LR), and negative LR (-LR) to estimate measures of precision of our clinical decision rule in the validation cohort. RESULTS Factors associated with MDR urinary pathogen included sex, recent hospitalization, nursing home residency, and catheter placement. Using our previously defined threshold of greater than 1 risk factor, the adjusted model in the validation cohort identified that only nursing home residency was associated with positive MDR pathogen (adjusted odds ratio = 4.13; 95% CI = 1.95-8.77). The clinical decision rule in the validation cohort yielded a sensitivity of 56.4%, specificity of 66.3%, +LR of 1.7, and -LR of 0.7. Conclusion and Relevance: Our clinical decision rule to identify patients at risk for MDR urinary pathogens was unable to be validated in the setting of different antimicrobial resistance patterns. Future studies should evaluate an improved clinical decision rule identifying risk factors associated with MDR pathogens that performs well in varying patient populations.
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Affiliation(s)
- Brett A Faine
- 1 University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Nicholas Mohr
- 1 University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | | | - Ari S Gao
- 3 Washington University in St Louis School of Medicine, MO, USA
| | - Stephen Y Liang
- 3 Washington University in St Louis School of Medicine, MO, USA
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Rajivgandhi G, Maruthupandy M, Manoharan N. Detection of TEM and CTX-M genes from ciprofloxacin resistant Proteus mirabilis and Escherichia coli isolated on urinary tract infections (UTIs). Microb Pathog 2018; 121:123-130. [DOI: 10.1016/j.micpath.2018.05.024] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 05/13/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022]
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A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis. Antimicrob Agents Chemother 2018; 62:AAC.01989-17. [PMID: 29378708 PMCID: PMC5913993 DOI: 10.1128/aac.01989-17] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 01/22/2018] [Indexed: 01/15/2023] Open
Abstract
Increasing antimicrobial resistance among uropathogens limits treatment options for patients with complicated urinary tract infection (cUTI). Plazomicin, a new aminoglycoside, has in vitro activity against multidrug-resistant Enterobacteriaceae, including isolates resistant to currently available aminoglycosides, as well as extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae. We evaluated the efficacy and safety of plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to receive intravenous plazomicin (10 or 15 mg/kg of body weight) or intravenous levofloxacin (750 mg) once daily for 5 days. Coprimary efficacy endpoints were microbiological eradication at the test of cure (TOC; 5 to 12 days after the last dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME) populations. Overall, 145 patients were randomized to treatment. In the groups receiving plazomicin at 10 mg/kg, plazomicin at 15 mg/kg, and levofloxacin, microbiological eradication rates were, respectively, 50.0% (6 patients with microbiological eradication at TOC/12 patients treated [95% confidence interval {CI}, 21.1 to 78.9%]), 60.8% (31/51 [95% CI, 46.1 to 74.2%]), and 58.6% (17/29 [95% CI, 38.9 to 76.5%]) in the MITT population and 85.7% (6/7 [95% CI, 42.1 to 99.6%]), 88.6% (31/35 [95% CI, 73.3 to 96.8%]), and 81.0% (17/21 [95% CI, 58.1 to 94.6%]) in the ME population. In the MITT population, 66.7% (95% CI, 34.9 to 90.1%), 70.6% (95% CI, 56.2 to 82.5%), and 65.5% (95% CI, 45.7 to 82.1%) of the patients in the three groups, respectively, were assessed by the investigator to be clinically cured at TOC. Adverse events were reported in 31.8%, 35.1%, and 47.7% of the patients in the three groups, respectively. Serum creatinine values were generally stable over the course of the study. No plazomicin-treated patients with evaluable audiometry data had postbaseline sensorineural, conductive, or mixed hearing loss. In summary, plazomicin demonstrated microbiological and clinical success and an overall safety profile supportive of further clinical development. (This study has been registered at ClinicalTrials.gov under identifier NCT01096849.)
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Community-acquired urinary tract infections due to extended-spectrum β -lactamase-producing organisms in United Arab Emirates. Travel Med Infect Dis 2018; 22:46-50. [DOI: 10.1016/j.tmaid.2018.01.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 12/16/2017] [Accepted: 01/25/2018] [Indexed: 12/18/2022]
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Chaudhary M, Ayub SG, Mir MA. CSE-1034 versus Ceftriaxone: Efficacy and Safety Analysis from a Randomized, Open-labeled Phase III Study in Complicated Urinary Tract Infections. J Glob Infect Dis 2018; 10:188-195. [PMID: 30581259 PMCID: PMC6276312 DOI: 10.4103/jgid.jgid_98_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective: The aim of this study was to determine the clinical outcome, microbiological outcome and safety profile of CSE-1034, a novel combination of Ceftriaxone, Sulbactam and EDTA in patients with complicated urinary tract infections (cUTI). Materials and Methods: This was a randomized, controlled, open-labeled Phase-3 trial with the primary objective of assessing the efficacy and safety of CSE-1034 versus Ceftriaxone for the empirical treatment of cUTI. Adult cUTI patients were randomized to receive either intravenous dose of CSE-1034 or Ceftriaxone. The primary end point was composite cure rate (clinical response and bacterial eradication) in mMITT population at test of cure (TOC) visit. Secondary measures included verification of primary endpoint across other visits in different population sets, safety of patients and treatment duration. Results: Overall, 204 patients were enrolled in the study and received one of the two treatments. At primary endpoint (TOC visit), the composite cure rate was much higher in CSE-1034 treatment arm compared to Ceftriaxone arm i.e. 97% (68/70) vs 83% (58/71) (treatment difference 12.6%; 95% CI: 5.9% to 26.4%). The adverse events (AEs) rates reported in two treatment arms were 21% in CSE-1034 and 36% in Ceftriaxone groups. Additionally, the treatment duration in CSE-1034 arm was significantly less (P < 0.05). Conclusions: CSE-1034 3 g every 24 h showed a high favorable clinical and bacteriological response, and 95% CI around the treatment difference prove the superiority of CSE-1034 vs. Ceftriaxone for the treatment of cUTI. Therefore, CSE-1034 provides an effective alternative in the treatment of patients with cUTI.
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Affiliation(s)
- Manu Chaudhary
- Department of Clinical Research, Venus Remedies, Panchkula, Haryana, India
| | | | - Mohd Amin Mir
- Department of Clinical Research, Venus Remedies, Panchkula, Haryana, India
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Erdem I, Kara Ali R, Ardic E, Elbasan Omar S, Mutlu R, Topkaya AE. Community-acquired Lower Urinary Tract Infections: Etiology, Antimicrobial Resistance, and Treatment Results in Female Patients. J Glob Infect Dis 2018; 10:129-132. [PMID: 30166811 PMCID: PMC6100335 DOI: 10.4103/jgid.jgid_86_17] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background/Purpose: Most community-acquired urinary tract infections (UTIs) are usually treated empirically. The knowledge of antibiotic resistance patterns of the microorganisms causing UTI is essential for defining the empirical treatment. Objective: The aim of the present study is to determine the distribution of bacterial strains isolated from lower UTIs and their resistance patterns against commonly used antimicrobial agents and treatment results in female patients. Subjects and Methods: This is a retrospective analysis of medical case records of 90 female patients with lower UTI for a period of 4 years from January 2013 to December 2016 in a tertiary care hospital in the Trakya region of Turkey. Results: The most common causative agent was Escherichia coli (66.6% of cases) followed by Klebsiella pneumoniae (16.6%). Fosfomycin was the most active agent against E. coli (resistant isolates: 5.5%), followed by nitrofurantoin (resistant isolates: 7.4%). Extended-spectrum beta-lactamases (ESBLs) production was observed in 29 (32.2%) isolates (22 in E. coli, 6 in K. pneumoniae, and 1 in Enterobacter spp.). The antimicrobial resistance rates among ESBL-producing E. coli isolates for trimethoprim-sulfamethoxazole, ciprofloxacin, fosfomycin, and nitrofurantoin were 77.7%, 72.7%, 13.6%, and 18.2%, respectively (P < 0.05). The estimated microbiological eradication rates for nitrofurantoin and fosfomycin were 89.7% and 83.8%, respectively. Conclusions: The results of the present study indicate that nitrofurantoin and fosfomycin may be considered for empirical therapy of lower UTIs in Trakya region of Turkey.
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Affiliation(s)
- Ilknur Erdem
- Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Ridvan Kara Ali
- Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Enes Ardic
- Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Senay Elbasan Omar
- Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Reyhan Mutlu
- Department of Medical Microbiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
| | - Aynur Eren Topkaya
- Department of Medical Microbiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
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Genovese C, Davinelli S, Mangano K, Tempera G, Nicolosi D, Corsello S, Vergalito F, Tartaglia E, Scapagnini G, Di Marco R. Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections. J Chemother 2017; 30:107-114. [PMID: 29078739 DOI: 10.1080/1120009x.2017.1393587] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Urinary tract infections (UTIs) are an economic burden for public health. The increasing prevalence of resistant bacteria which cause UTIs may be related to the inappropriate prescription of antibiotics. The aim of this preliminary study was to evaluate whether three different combinations of plant extracts plus d-mannose are effective in preventing the recurrence of UTIs. Three groups of patients received three combinations of plant extracts in conjunction with d-mannose. These were: berberine, arbutin and birch (group A); berberine, arbutin, birch and forskolin (group B); and proanthocyanidins (group C). The clinical recurrence of cystitis at the end of treatment and during follow-up was determined by comparison with baseline measurements using the microbiological assessment of urine samples, vaginal swabs and vaginal smear slides. Patients in groups A and B had a lower incidence of episodes of recurrent cystitis during treatment and follow-up, samples with a significantly lower median bacterial load and a reduction of the grade of lactobacillary flora compared to patients in group C.
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Affiliation(s)
- Carlo Genovese
- a Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy
| | - Sergio Davinelli
- b Department of Medicine and Health Sciences , University of Molise , Campobasso , Italy
| | - Katia Mangano
- a Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy
| | - Gianna Tempera
- a Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy
| | - Daria Nicolosi
- a Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy
| | - Salvatore Corsello
- c Obstetrics & Gynecology Division , "Castiglione Prestianni" Hospital , Bronte , Italy
| | - Franca Vergalito
- b Department of Medicine and Health Sciences , University of Molise , Campobasso , Italy
| | - Edoardo Tartaglia
- b Department of Medicine and Health Sciences , University of Molise , Campobasso , Italy
| | - Giovanni Scapagnini
- b Department of Medicine and Health Sciences , University of Molise , Campobasso , Italy
| | - Roberto Di Marco
- b Department of Medicine and Health Sciences , University of Molise , Campobasso , Italy
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Delbet JD, Lorrot M, Ulinski T. An update on new antibiotic prophylaxis and treatment for urinary tract infections in children. Expert Opin Pharmacother 2017; 18:1619-1625. [PMID: 28954556 DOI: 10.1080/14656566.2017.1383383] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION This review focuses on the treatment of urinary tract infections (UTI) in children and in particular its recent changes. Areas covered: Acute pyelonephritis, acute cystitis and asymptomatic bacteriuria or asymptomatic infections have to be clearly distinguished. Prompt treatment is required in pyelonephritis and cystitis, but not in asymptomatic bacteriuria or infection, in order to avoid selection of more virulent strains. This concept should be considered even in immunocompromised or bedridden children. In case of pyelonephritis, there should be no delay in beginning the antibiotic treatment in order to decrease the risk of long term complication, such as renal scars. Predisposing conditions for UTI, such as voiding anomalies and urinary tract malformation should be carefully evaluated. Expert opinion: One major concern is the increasing resistance to 3rd generation cephalosporins. Therefore overconsumption in low-risk settings should be absolutely avoided. The prevalence of infections with E. coli producing extended spectrum ß-lactamase (ESBL) is increasing and pediatricians should be aware about the specific treatment options. Any recommendation about (initial) antibiotic treatment should be regularly updated and adapted to local resistance profiles and to economic factors in different health systems.
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Affiliation(s)
- Jean Daniel Delbet
- a Pediatric Nephrology Unit , Trousseau Hospital and DHU i2B Inflammation-Immunopathology-Biotherapy , Paris , France.,b University Pierre and Marie Curie , Paris , France
| | - Mathie Lorrot
- c General Pediatrics and Infectious Diseases , Armand Trousseau Hospital , Paris , France
| | - Tim Ulinski
- a Pediatric Nephrology Unit , Trousseau Hospital and DHU i2B Inflammation-Immunopathology-Biotherapy , Paris , France.,b University Pierre and Marie Curie , Paris , France
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Delcaru C, Podgoreanu P, Alexandru I, Popescu N, Măruţescu L, Bleotu C, Mogoşanu GD, Chifiriuc MC, Gluck M, Lazăr V. Antibiotic Resistance and Virulence Phenotypes of Recent Bacterial Strains Isolated from Urinary Tract Infections in Elderly Patients with Prostatic Disease. Pathogens 2017; 6:E22. [PMID: 28561794 PMCID: PMC5488656 DOI: 10.3390/pathogens6020022] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 05/18/2017] [Accepted: 05/25/2017] [Indexed: 11/17/2022] Open
Abstract
Acute bacterial prostatitis is one of the frequent complications of urinary tract infection (UTI). From the approximately 10% of men having prostatitis, 7% experience a bacterial prostatitis. The purpose of this study was to investigate the prevalence of uropathogens associated with UTIs in older patients with benign prostatic hyperplasia and to assess their susceptibility to commonly prescribed antibiotics as well as the relationships between microbial virulence and resistance features. Uropathogenic Escherichia coli was found to be the most frequent bacterial strain isolated from patients with benign prostatic hyperplasia, followed by Enterococcus spp., Enterobacter spp., Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens. Increased resistance rates to tetracyclines, quinolones, and sulfonamides were registered. Besides their resistance profiles, the uropathogenic isolates produced various virulence factors with possible implications in the pathogenesis process. The great majority of the uropathogenic isolates revealed a high capacity to adhere to HEp-2 cell monolayer in vitro, mostly exhibiting a localized adherence pattern. Differences in the repertoire of soluble virulence factors that can affect bacterial growth and persistence within the urinary tract were detected. The Gram-negative strains produced pore-forming toxins-such as hemolysins, lecithinases, and lipases-proteases, siderophore-like molecules resulted from the esculin hydrolysis and amylases, while Enterococcus sp. strains were positive only for caseinase and esculin hydrolase. Our study demonstrates that necessity of investigating the etiology and local resistance patterns of uropathogenic organisms, which is crucial for determining appropriate empirical antibiotic treatment in elderly patients with UTI, while establishing correlations between resistance and virulence profiles could provide valuable input about the clinical evolution and recurrence rates of UTI.
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Affiliation(s)
- Cristina Delcaru
- Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest (ICUB), 91-95 Independenţei Avenue, 0500088 Bucharest, Romania.
| | - Paulina Podgoreanu
- Iancului Private Laboratory, 060101 Bucharest, Romania.
- Department of Microbiology & Immunology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Lane, Sector 6, 060101 Bucharest, Romania.
| | - Ionela Alexandru
- Iancului Private Laboratory, 060101 Bucharest, Romania.
- Department of Microbiology & Immunology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Lane, Sector 6, 060101 Bucharest, Romania.
| | - Nela Popescu
- Iancului Private Laboratory, 060101 Bucharest, Romania.
| | - Luminiţa Măruţescu
- Department of Microbiology & Immunology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Lane, Sector 6, 060101 Bucharest, Romania.
| | - Coralia Bleotu
- Ştefan S. Nicolau Institute of Virology, 285 Mihai Bravu Avenue, 030304 Bucharest, Romania.
| | - George Dan Mogoşanu
- Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Romania.
| | - Mariana Carmen Chifiriuc
- Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest (ICUB), 91-95 Independenţei Avenue, 0500088 Bucharest, Romania.
- Department of Microbiology & Immunology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Lane, Sector 6, 060101 Bucharest, Romania.
| | | | - Veronica Lazăr
- Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest (ICUB), 91-95 Independenţei Avenue, 0500088 Bucharest, Romania.
- Department of Microbiology & Immunology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Lane, Sector 6, 060101 Bucharest, Romania.
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Cammarata M, Thyer R, Lombardo M, Anderson A, Wright D, Ellington A, Brodbelt JS. Characterization of trimethoprim resistant E. coli dihydrofolate reductase mutants by mass spectrometry and inhibition by propargyl-linked antifolates. Chem Sci 2017; 8:4062-4072. [PMID: 29967675 PMCID: PMC6020862 DOI: 10.1039/c6sc05235e] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 03/24/2017] [Indexed: 12/12/2022] Open
Abstract
Native mass spectrometry, size exclusion chromatography, and kinetic assays were employed to study trimethoprim resistance in E. coli caused by mutations P21L and W30R of dihydrofolate reductase.
Pathogenic Escherichia coli, one of the primary causes of urinary tract infections, has shown significant resistance to the most popular antibiotic, trimethoprim (TMP), which inhibits dihydrofolate reductase (DHFR). The resistance is modulated by single point mutations of DHFR. The impact of two clinically relevant mutations, P21L and W30R, on the activity of DHFR was evaluated via measurement of Michaelis–Menten and inhibitory kinetics, and structural characterization was undertaken by native mass spectrometry with ultraviolet photodissociation (UVPD). Compared to WT-DHFR, both P21L and W30R mutants produced less stable complexes with TMP in the presence of co-factor NADPH as evidenced by the relative abundances of complexes observed in ESI mass spectra. Moreover, based on variations in the fragmentation patterns obtained by UVPD mass spectrometry of binary and ternary DHFR complexes, notable structural changes were localized to the substrate binding pocket for W30R and to the M20 loop region as well as the C-terminal portion containing the essential G–H functional loop for the P21L mutant. The results suggest that the mutations confer resistance through distinctive mechanisms. A novel propargyl-linked antifolate compound 1038 was shown to be a reasonably effective inhibitor of the P21L mutant.
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Affiliation(s)
- Michael Cammarata
- Department of Chemistry , University of Texas , Austin , TX 78712 , USA .
| | - Ross Thyer
- Center for Systems and Synthetic Biology , University of Texas , Austin , TX 78712 , USA
| | - Michael Lombardo
- Department of Pharmaceutical Sciences , University of Connecticut , Storrs , CT 06269 , USA
| | - Amy Anderson
- Department of Pharmaceutical Sciences , University of Connecticut , Storrs , CT 06269 , USA
| | - Dennis Wright
- Department of Pharmaceutical Sciences , University of Connecticut , Storrs , CT 06269 , USA
| | - Andrew Ellington
- Center for Systems and Synthetic Biology , University of Texas , Austin , TX 78712 , USA
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Morris BJ, Krieger JN, Klausner JD. CDC's Male Circumcision Recommendations Represent a Key Public Health Measure. GLOBAL HEALTH, SCIENCE AND PRACTICE 2017; 5:15-27. [PMID: 28351877 PMCID: PMC5478224 DOI: 10.9745/ghsp-d-16-00390] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 01/31/2017] [Indexed: 12/20/2022]
Abstract
Frisch and Earp, opponents of male circumcision, have criticized draft recommendations from the CDC that advocate counseling men and parents of newborn boys in the United States about the benefits and risks of male circumcision. We provide a rebuttal to Frisch and Earp's criticisms and contend that the recommendations are entirely appropriate and merit consideration for policy development.
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Affiliation(s)
- Brian J Morris
- School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia.
| | - John N Krieger
- University of Washington School of Medicine and VA Puget Sound Health Care System, Section of Urology, Seattle, WA, USA
| | - Jeffrey D Klausner
- Department of Epidemiology, Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, CA, USA
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