4.6 Article

In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia

Journal

ANTIBIOTICS-BASEL
Volume 10, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/antibiotics10020181

Keywords

antimicrobial resistance; β -lactamase inhibitor; broad-spectrum β -lactamase; resistance gene; Enterobacteriaceae

Funding

  1. University of Malaya Research Fund [RU008-2018]
  2. Shionogi Singapore Pte. Ltd.

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The prevalence of ESBL-producing Enterobacteriaceae has impacted the efficacy of beta-lactam antibiotics in treating UTIs. This study showed high rates of resistance to various beta-lactam antibiotics in ESBL-producing E. coli and K. pneumoniae isolated from UTIs, with carbapenems remaining the most effective treatment option. Flomoxef may serve as a potential alternative to carbapenems for treating UTIs caused by ESBL-producers in Malaysia.
The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of beta-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established beta-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76-80%), ticarcillin-clavulanate (58-76%), and piperacillin-tazobactam (48-50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 mu g/mL to 128 mu g/mL) for both species. The ESBL genes bla(CTX-M) and bla(TEM) were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas bla(SHV) was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.

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