Dataset Information

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli.

ABSTRACT: Cefmetazole is active against extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla _CTX-M was detected as the extended-spectrum β-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

SUBMITTER: Hayakawa K

PROVIDER: S-EPMC10583665 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing <i>Escherichia coli</i>.

Hayakawa Kayoko K Matsumura Yasufumi Y Uemura Kohei K Tsuzuki Shinya S Sakurai Aki A Tanizaki Ryutaro R Shinohara Koh K Hashimoto Takehiro T Hase Ryota R Matono Takashi T Kato Hideaki H Mawatari Momoko M Hara Hiroshi H Hamada Yukihiro Y Saito Sho S Ohmagari Norio N Doi Yohei Y

Antimicrobial agents and chemotherapy 20230913 10

Cefmetazole is active against extended-spectrum β-lactamase-producing <i>Escherichia coli</i> (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcome ...[more]

PMID: 37702483

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Project description:IntroductionFinding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future.Methods and analysisThe main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli.Ethics and disseminationEthical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals.DiscussionThis project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy.Trial registration numberNCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Project description:ImportanceExtended-spectrum β-lactamase (ESBL)-producing Escherichia coli is considered a leading pathogen contributing to the global burden of antimicrobial resistance.ObjectiveTo better understand factors associated with the heterogeneity of community-acquired ESBL-producing E coli urinary tract infections (UTIs) in France.Design, setting, and participantsThis cross-sectional study performed from January 1 to December 31, 2021, was based on data collected via PRIMO (Surveillance and Prevention of Antimicrobial Resistance in Primary Care and Nursing Homes), a nationwide clinical laboratory surveillance system in France. Strains of E coli isolated from community urine samples from January 1 to December 31, 2019, from 59 administrative departments of metropolitan France were included.Main outcomes and measuresQuasi-Poisson regression models were used to assess the associations between several ecological factors available on government and administration websites between 2010 and 2020 (demographic population structure, living conditions, baseline health care services, antibiotic consumptions, economic indicators, animal farming density, and environmental characteristics) and the number of ESBL-producing E coli strains isolated from urine samples of individuals with community-acquired UTI in 2019.ResultsAmong 444 281 E coli isolates from urine samples tested in 1013 laboratories, the mean prevalence of ESBL-producing E coli was 3.0% (range, 1.4%-8.8%). In an adjusted model, the number of community-acquired ESBL-producing E coli UTIs in each department was positively associated with the percentage of children younger than 5 years (adjusted β1 coefficient, 0.112 [95% CI, 0.040-0.185]; P = .004), overcrowded households (adjusted β1 coefficient, 0.049 [95% CI, 0.034 to 0.062]; P < .001), consumption of fluoroquinolones (adjusted β1 coefficient, 0.002 [95% CI, 0.001-0.002]; P < .001), and tetracyclines (adjusted β1 coefficient, 0.0002 [0.00004 to 0.00039]; P = .02), and poultry density (adjusted β1 coefficient, 0.0001 [95% CI, 0.0001-0.0002]; P < .001). The social deprivation index (adjusted β1 coefficient, -0.115 [95% CI, -0.165 to -0.064]; P < .001) and the proportion of water surface area (adjusted β1 coefficient, -0.052 [-0.081 to -0.024]; P = .001) were negatively associated with a higher number of community-acquired ESBL-producing E coli UTIs.Conclusions and relevanceThe findings of this cross-sectional study suggest that multiple human health, animal health, and environmental factors are associated with the occurence of community-acquired ESBL E coli UTI. Strategies to mitigate ESBL in the community should follow the One Health approach and address the role played by fluoroquinolones, tetracycline use, poultry density, overcrowded households, and preschool-aged children.

Dataset Information

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli.

Publications

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing <i>Escherichia coli</i>.

Similar Datasets

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