Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections, "Beyond the Abstract," by Filip Jansåker and Niels Frimodt-Møller

BERKELEY, CA (UroToday.com) - This article is from a small prospective observational study that shows pivmecillinam (as one of few oral available drugs) to retain its clinical effect in lower UTIs caused by ESBL-producing Enterobacteriaceae.

Pivmecillinam is a prodrug to amidino penicillin, or mecillinam. It has good pharmacokinetic and pharmacodynamic properties for infections in the urinary tract, with excellent clinical effect.[1] Pivmecillinam is recommended as a first line drug for the treatment of lower UTI in the recent international guidelines, and is also, in Denmark, recommended for acute uncomplicated pyelonephritis.

The increasing prevalence of resistance to many antibiotics, e.g., as in ESBL-producing Enterobacteriaceae, is of rising concern since many of the orally available antimicrobial agents previously used against UTIs no longer can be given empirically in many countries. In contrast, pivmecillinam is one of few orally available drugs that keeps displaying low resistance rates, and interestingly low probability of clonal spread of resistance.[2] Pivmecillinam has good in vitro activity against ESBL-producing Enterobacteriaceae,[3] and our study shows that pivmecillinam, in a dose of 400 mg, 3 times a day, has good clinical and bacteriological effect. However, our study is a small observational study, and larger randomized studies are needed to confirm and enforce this evidence.

We believe pivmecillinam (i.e., 400 mg, 3 times a day) to be a valuable and effective orally available option against ESBL-producing Enterobacteriaceae causing lower UTI. Therefore, we continue to recommend and use pivmecillinam as first-line option in Denmark against UTIs, and would recommend other countries to do so.

We will soon be initiating a randomized double-blinded study on the duration of treatment of pivmecillinam for uncomplicated urinary tract infections in primary care, and hope to provide further valid evidence on the effect on pivmecillinam on ESBL-producing Enterobacteriaceae. We recommend future larger randomized studies on pivmecillinam’s effect on ESBL-producing Enterobacteriaceae causing UTI and its clinical effect on pyelonephritis.

References:

  1. Ferry SA et al. Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project. Scandinavian Journal of Primary Health Care. 2007 PubMed PMID: 17354160. Pubmed Central PMCID: 3389454.
  2. Poulsen HO, Johansson A, Granholm S, Kahlmeter G, Sundqvist M. High genetic diversity of nitrofurantoin- or mecillinam-resistant Escherichia coli indicates low propensity for clonal spread. Journal of Antimicrobial Chemotherapy. 2013 Sep;68(9):1974-7.
  3. Lampri N, Galani I, Poulakou G, Katsarolis I, Petrikkos G, Giamarellou H, et al. Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Journal of Antimicrobial Chemotherapy. 2012 Oct;67(10):2424-8.

Written by:
Filip Jansåker and Niels Frimodt-Møller as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark

Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections - Abstract

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