Antimicrobial susceptibilities of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin

Abstract

Purpose: The appearance of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria in urinary tract infection (UTI) constitutes an important therapeutic challenge. The aim of this study was to describe drug susceptibility profiles of ESBL-producing bacteria isolated from urine samples. We also determined the antimicrobial co-resistance to several agents, including fosfomycin.

Methods: The computerized database was used to identify ESBL-positive urine samples. We analyzed E. coli and Klebsiella isolates obtained from urine cultures, and duplicate isolates and isolates not tested against fosfomycin were excluded. The cases were further categorized according to UTI definition [community-acquired (CoA) UTI, community-onset health care-associated (HCA) UTI, and hospital-acquired (HA) UTI]. ESBL isolates were stratified according to their origin into two groups: urology and non-urology isolates.

Results: Antimicrobial susceptibilities of the strains to fosfomycin were tested in 277 ESBL-positive strains, 217 ESBL-EC strains, and 60 ESBL-KP strains. The most effective agents were carbapenems, such as imipenem and meropenem. The least active substances were ciprofloxacin (20.7 %), levofloxacin (22.7 %), trimethoprim-sulfamethoxazole (34.3 %), and ampicillin-clavulanate (42.9 %). Overall, 243 out of the 277 (87.7 %) isolates tested were susceptible to fosfomycin. Higher fosfomycin sensitivity was observed in E. coli (94.9 %) compared to Klebsiella (61.7 %) (p = 0.001). ESBL-positive isolates from urological (68 isolates) and non-urological patients (209 isolates) showed similar susceptibility profiles. Other than carbapenems, isolates from CoA-UTI showed higher sensitivity to fosfomycin (100 %) and nitrofurantoin (93.1 %), isolates from HCA-UTI showed higher sensitivity to amikacin (94.1 %), and isolates from HA-UTI showed overall poor sensitivity to antibiotics.

Conclusions: Fosfomycin could be an alternative treatment option for UTIs related to ESBL-producing E. coli spp. and CoA-UTI, but not for UTIs related to ESBL-producing Klebsiella spp. Antimicrobial susceptibilities of ESBL-producing strains were different according to the UTI classification. Fosfomycin showed decreased activity against isolates from HCA-UTI and HA-UTI. However, further clinical verification is required to assess the clinical efficacy of fosfomycin for the treatment of UTIs caused by ESBL-producing E. coli isolates.