Reduced Susceptibility to Cefepime in Clinical Isolates of Enterobacteriaceae Producing OXA-1 Beta-Lactamase

Abstract

An increase of Enterobacteriaceae isolates with reduced susceptibility to cefepime (FEP) and amoxicillin/clavulanate (AMC) has been observed in our area. The aim of this study was to characterize this antibiotic resistance phenotype and its molecular epidemiology. A total of 33 Enterobacteriaceae strains were studied. blaOXA-1 genes and their genetic environment were analyzed by polymerase chain reaction (PCR) and sequencing. Plasmids were transferred by conjugation and/or transformation and classified using PCR-based inc/rep typing and IncF subtyping. Escherichia coli isolates were typed by phylogroup, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Outer membrane proteins were studied by sodium dodecylsulfate-polyacrylamide gel electrophoresis and expression of blaOXA-1 genes by reverse transcription-PCR. FEP minimum inhibitory concentration yielded values of 1-16 mg/L. Twenty-nine (87.9%) isolates produced OXA-1, of which 24 (82.7%) were located in class 1 integron, and 9 (27.3%) produced TEM-1. Among the 24 E. coli OXA-1-producers, PFGE revealed two main clusters: one belonged to C-ST88 and the other to B23-ST131. Thirteen plasmids containing blaOXA-1 were transferred, nine belonged to IncF replicon (4 F2:A1:B-, 2 F1:A1:B1, 1 F1:A2:B-, 1 F18:A2:B1, 1 F5:A-:B1) and four were nontypeable. In conclusion, reduced susceptibility to FEP was mostly due to OXA-1 beta-lactamase. In E. coli, this increase is mainly due to the dissemination of two clones, which have captured different IncF plasmids. Among non-E. coli strains, five isolates produced OXA-1 and one isolate produced only TEM-1.

Panel strain ofKlebsiella pneumoniaefor beta-lactam antibiotic evaluation: their phenotypic and genotypic characterization

“…The bla OXA-1 gene has been frequently found to be associated with genes encoding ESBL’s. This, along with the OmpK36 porin loss can cause reduced susceptibility to cefepime (Beceiro et al, 2011; Torres et al, 2016). bla OXA1 was found in the following genetic environment, IS26-catB4-bla OXA-1 -aac (6′)- Ib-cr-IS26 .…”

“…Similar to the strainYMC2011/7/B774, this strain has bla CTX-M15 and bla OXA-1 along with the bla SHV-187 . Reduced susceptibility to cefepime is due to the bla OXA-1 (Torres et al, 2016). The presence of multiple aminoglycoside resistance genes such as aac (6′) Ib-cr , strA , strB , oqxA , oqxB and QnrB66 offered resistance to ciprofloxacin.…”

ST37 Klebsiella Pneumoniae : Development of Carbapenem Resistance in Vivo During Antimicrobial Therapy in Neonates

“…Madhan Sugumar [30] found that bla OX A-1 β-lactamase-producing strains were resistant to piperacillin/tazobactam (100%), levofloxacin (91.6%), amikacin (75%), cefoxitin (50%), ertapenem (25%), imipenem (16.6%) and meropenem (16.6%). Eva Torres [33] reported that reduced susceptibility to cefepime was mostly due to bla OXA-1 β-lactamase in E. coli. However, the relationship between the bla OXA-1 gene and carbapenems has never been reported.…”

Antimicrobial Resistance and Molecular Characterization of Extended-Spectrum β-Lactamases ofEscherichia coliandKlebsiellaspp. Isolates from Urinary Tract Infections in Southern Brazil

“…6 The OXA-ESBL type has been found more frequently in Pseudomonas aeruginosa, but with its genes distributed on plasmids; OXA are currently found in several members of the Enterobacteriaceae family too. 7,8 Despite worldwide distribution of ESBL, their epidemiology varies according to the geographic region. The enzymes of the CTX-M group currently overlap with other ESBL and have expanded beyond hospital borders.…”