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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model

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  1. Molecular basis of antifungal drug resistance in yeasts

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  2. Genetic characterization confirms sporadic occurrence of vancomycin-resistant Enterococcus faecalis in Copenhagen, Denmark

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  3. Hyperbaric oxygen therapy augments tobramycin efficacy in experimental Staphylococcus aureus endocarditis

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  4. Antimicrobial resistance in the Bacteroides fragilis group in faecal microbiota from healthy Danish children

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  1. Effects of Antibiotics on the Intestinal Microbiota of Mice

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  2. Community-acquired meningitis caused by beta-haemolytic streptococci in adults: a nationwide population-based cohort study

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Pivmecillinam, a pro-drug of mecillinam, has been used extensively in Scandinavia for the treatment of acute lower urinary tract infections (UTIs) caused by Enterobacterales. It is still an attractive first-line drug for the empirical treatment of UTIs owing to the low prevalence of resistance as well as its favourable impact on the intestinal microbiota as a pro-drug and good in vitro efficacy against extended-spectrum β-lactamase (ESBL)- and plasmid-mediated AmpC β-lactamase-producing Escherichia coli. However, optimal dosing of pivmecillinam as well as its in vivo efficacy against UTIs caused by multidrug-resistant (MDR) broad-spectrum β-lactamase-producing E. coli has not been thoroughly studied. In this study, the efficacy of two mimicked human dosing regimens of pivmecillinam (200 mg and 400 mg three times daily) against clinical E. coli strains, including isolates producing ESBLs (CTX-M-14 and CTX-M-15), plasmid-mediated AmpCs (CMY-4 and CMY-6) and carbapenemases (NDM-1 and VIM-29), in a murine UTI model was compared. Both dosing regimens reduced the number of CFU/mL in urine for all strains, including mecillinam-resistant strains. Combining the effect for all six strains showed no significant differences in effect between doses for all three fluids/organs, but for each dose there was a highly significant effect in urine, kidney and bladder compared with vehicle-treated mice. Overall, this highlights the need for further studies to elucidate the role of mecillinam in the treatment of infections caused by MDR E. coli producing broad-spectrum β-lactamases, including specific carbapenemases.

Original languageEnglish
JournalInternational Journal of Antimicrobial Agents
Volume55
Issue number2
Pages (from-to)105851
Number of pages6
ISSN0924-8579
DOIs
Publication statusPublished - Feb 2020

    Research areas

  • Carbapenemase, ESBL, In vivo, Mecillinam, Multidrug-resistant, UTI model

ID: 58999798