Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

Abstract

Background: Extended Spectrum βeta-lactamase (ESBL)-producing Enterobacteriaceae causing urinary tract infections (UTIs) appear resistant to many common oral agents. There is a growing need to discover new antibiotics to combat with emerging antibiotic resistance problem. Until the discovery of new antimicrobials, we can bring back forgotten antibiotics to our clinical formulary. Pivmecillinam (prodrug of mecillinam), an oral antimicrobial agent is effective against ESBL producing organisms. We analysed the sensitivity rates of ESBL-producing Enterobacteriaceae from urine samples to mecillinam and to document if pivmecillinam is a suitable alternative option in the treatment of UTI. Materials/methods: This retrospective study was conducted from September 2015to September 2017. Data were collected from the pathology information system.Antimicrobial sensitivity testing on ESBL-producing Enterobacteriaceae isolates was carried out by disc diffusion method in accordance with The European Committee on Antimicrobial Susceptibility Testing. Results:A total of 986 ESBL-producing Enterobacteriaceae were tested for mecillinam during the study period. Of 986 organisms, Escherichia coli was the most common organism (889); followed by Klebsiella species (71) and others Enterobacteriaceae (26). Mecillinam sensitivity was found in 96% Escherichia coli (855/889 isolates), 83%Klebsiella species (59/71 isolates) and 88% other Enterobacteriaceae (23/26 isolates).Overall 95% (935/986 isolates) of ESBL-producing urinary isolates were sensitive to mecillinam.Conclusions: Pivmecillinam appears to be suitable option to treat ESBL-producing Enterobacteriaceae causing uncomplicated UTI. Our results showed low resistance rate to mecillinam. We recommend the use of pivmecillinam in uncomplicated UTIs because of ESBL-producing Enterobacteriaceae. More studies on in vitro activity of mecillinam against ESBL producing organism and its use and clinical outcome should be tried in future.

Analysis of drug resistance genes of integrons in clinical isolates of Escherichia coli from elderly bloodstream infections

“…Moreover, it can recombine drug resistance genes in multiple ways, aggravating the spread of resistance genes among bacteria which is the root cause of bacterial multi-drug resistance (14,15). The present study showed that the detection rate of ESBLs-producing E. coli was 37.39% in bloodstream infections in elderly patients, which was lower than the detection rate of ESBLs-producing bacteria reported by Xia Fei et al (16,17). This may be related to the different elderly populations studied.…”

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

“…Although, in vivo activity has been demonstrated against S. saprophyticus [171]. Despite 95% susceptibility in ESBL-producing urinary isolates [172], treatment failure has been reported in susceptible strains (44% treatment failure in ESBL; 14% in non-ESBL) [173]. Resistance can arise following permeability changes or β-lactamase enzymes.…”

LC‐MS/MS methods for determination of unstable pivmecillinam and mecillinam in acidified human plasma: Application to a pharmacokinetic study

“…In vivo, this biologically inactive compound is hydrolyzed by nonspecific intestinal esterase to the biologically active mecillinam [6][7][8]. Contrary to most penicillin, mecillinam exerts a significant activity against Gram-negative organisms but low activity against Gram-positive bacteria [9][10][11]. Moreover, mecillinam also possesses a synergistic effect when used in combination with other β-lactam antibiotics [12,13], which would further enrich the treatment options of UTIs.…”