Objectives: Mecillinam is recommended in France as a first-line treatment for lower urinary tract infections, due to the large increase in resistance of Escherichia coli to other oral treatments, such as co-trimoxazole or fluoroquinolones, its limited impact on faecal microbiota and its stability in the presence of numerous β-lactamases. However, we recently identified several mecillinam-resistant E. coli isolates with a high-level expression penicillinase (HEP) phenotype that merit further study.
Patients And Methods: We studied two isogenic clinical isolates from one patient (one susceptible to mecillinam and one resistant to mecillinam) by WGS to determine the mechanism of mecillinam resistance and compared it with other mecillinam-resistant E. coli . We evaluated the synergistic combination of amoxicillin/clavulanate and mecillinam using a simple test, suitable for daily laboratory practice, to determine the MIC of this combination.
Results: We showed that the presence of an SNP in the promoter of the plasmidic TEM-1 β-lactamase gene is sufficient to confer resistance to mecillinam. This mechanism was present in 67% of HEP-phenotype E. coli tested. Combining mecillinam with amoxicillin/clavulanate abolished resistance, with an MIC compatible with clinical use. This association was not sensitive to the inoculum effect, in contrast to mecillinam alone.
Conclusions: An HEP phenotype can confer mecillinam resistance in vitro . This resistance is abolished, regardless of the inoculum, by combining mecillinam with amoxicillin/clavulanate, and can be easily tested in the laboratory. This combination may be used as an oral relay treatment of non-complicated pyelonephritis due to multiresistant E. coli strains.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dkx087 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pivmecillinam with Amoxicillin/Clavulanic acid as step down oral therapy in febrile Urinary Tract Infections caused by ESBL-producing Enterobacterales (PACUTI).
Trials
September 2023
Department of Clinical Sciences Helsingborg (AKVH), Faculty of Medicine, Lund University, Lund, Sweden.
Background: Oral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of pivmecillinam and amoxicillin/clavulanic acid is non-inferior to current alternatives for step-down therapy in adult patients with febrile urinary tract infection.
Methods: We plan to perform an investigator-initiated non-inferiority trial.
Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.
J Antimicrob Chemother
October 2021
Université de Paris, IAME, INSERM, F-75018 Paris, France.
Article Synopsis
- The study investigates how multi-drug resistant Enterobacterales affect the effectiveness of oral antibiotics for treating febrile urinary tract infections (FUTIs) in children, focusing on β-lactamase profiles and genotypes.
- A total of 251 ESBL-producing Enterobacterales isolates were analyzed for their susceptibility to various antibiotics, revealing that all were resistant to cefixime and cefpodoxime but that the combination of cefixime with amoxicillin/clavulanate restored susceptibility in most cases.
- The findings suggest that cefixime combined with amoxicillin/clavulanate is an effective treatment option, with no failures reported, and mecillinam combined with amoxicillin/clavulanate is recommended as an
Children with acute pyelonephritis need medical re-evaluation when home-treated with oral antibiotics.
Acta Paediatr
September 2021
Department of Paediatrics and Adolescence Medicine, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
Aim: To investigate the efficacy and safety of home-treatment with oral piv-mecillinam or amoxicillin-clavulanate in children with acute pyelonephritis.
Methods: Children aged over 6 months diagnosed with culture confirmed pyelonephritis at Danish Paediatric Departments were home-treated with piv-mecillinam (tablets) or amoxicillin-clavulanate (liquid or tablets). Follow-up was performed by phone (second treatment day) and clinical review of the patients in the hospital (day three).
Synergistic and bactericidal activities of mecillinam, amoxicillin and clavulanic acid combinations against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in 24-h time-kill experiments.
Int J Antimicrob Agents
January 2019
Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, SE 751 85 Uppsala, Sweden. Electronic address:
This study aimed to evaluate the potential synergistic and bactericidal effects of mecillinam in combination with amoxicillin and clavulanic acid against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Eight clinical E. coli isolates with varying susceptibility to mecillinam [minimum inhibitory concentrations (MICs) of 0.
View Article and Find Full Text PDFA combination of mecillinam and amoxicillin/clavulanate can restore susceptibility of high-level TEM-1-producing Escherichia coli to mecillinam.
J Antimicrob Chemother
July 2017
IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Objectives: Mecillinam is recommended in France as a first-line treatment for lower urinary tract infections, due to the large increase in resistance of Escherichia coli to other oral treatments, such as co-trimoxazole or fluoroquinolones, its limited impact on faecal microbiota and its stability in the presence of numerous β-lactamases. However, we recently identified several mecillinam-resistant E. coli isolates with a high-level expression penicillinase (HEP) phenotype that merit further study.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!