ABSTRACT
The widespread prevalence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli limits treatment options and is a worldwide problem. The aim of this study was to investigate the antimicrobial susceptibility and ESBL-type of 204 strains of CTX-M-type ESBLs-producing E. coli isolated from 2011 to 2017 in the Chubu region of Japan. Minimal inhibitory concentrations were determined in accordance with the guidelines of the Clinical and Laboratory Standards Institute. Genes encoding CTX-M group ß-lactamases were detected by PCR amplification. The CTX-M subtypes were determined using sequence analysis. The CTX-M-9 group was the most frequently detected ESBL group, and CTX-M-27 was the most frequently detected ESBL gene. CTX-M-15-producing strains showed significantly lower rates of susceptibility to tazobactam/piperacillin (TAZ/PIPC) than those by CTX-M-14 and -27-producing strains. Additional analysis of secondary ß-lactamases revealed that most of the OXA-1-positive strains were CTX-M-15-producing strains (94.7%). These strains displayed significantly lower susceptibility rates to TAZ/PIPC (47.4%), sulbactam/ampicillin (SBT/ABPC) (0.0%), and amikacin (AMK) (73.7%) than those by OXA-1-negative strains, suggesting that the high non-susceptibility rate of the CTX-M-15-producing strain was due to the co-carriage of OXA-1. The CTX-M-15-producing strains showed reduced susceptibility to TAZ/PIPC, SBT/ABPC, and AMK, presumably due to the co-carriage of OXA-1.
ABSTRACT
OBJECTIVES: To investigate the effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic (PK) model and to examine the relationship between the emergence of resistance and PK/pharmacodynamic parameters. METHODS: A wild-type and a GrlA mutant of S. aureus were exposed to the Japanese clinical dose of ciprofloxacin in an in vitro PK model, and the development of resistance was measured by population analysis. In addition, several doses of four quinolones (pazufloxacin, ciprofloxacin, levofloxacin and tosufloxacin) were tested against the GrlA mutant. All model simulations were single-dose design and were conducted over 24 h. RESULTS: Four quinolones were tested against the GrlA mutant, and a resistant population emerged after treatment with 250 mg pazufloxacin intravenous drip infusion, 600 mg ciprofloxacin intravenous drip infusion, 200 mg levofloxacin oral dosing and 150 mg tosufloxacin oral dosing. The emergence of a resistant population was not induced by treatment with 500 mg pazufloxacin intravenous drip infusion, 2,400 mg ciprofloxacin intravenous drip infusion, 400 mg levofloxacin oral dosing and 600 mg tosufloxacin oral dosing. Treatment with the clinical dose of ciprofloxacin induced the development of resistance in the GrlA mutant, but not in the wild-type strain. CONCLUSIONS: These data suggest that the frequency of acquisition of additional mutations differs between the wild-type and the GrlA mutant of S. aureus. Also, GrlA mutation predisposes S. aureus to develop high-level quinolone resistance.
