Time-Kill Curves of Enterobacteria Displaying Dissociated Resistance to Third Generation Cephalosporins.

MARCHISIO MARTÍN; RADICE MARCELA; GUTKIND GABRIEL; MENDEZ EMILCE; DI CONZA JOSÉ

New Orleans

Congreso; ASM MICROBE 2017; 2017

American Society for Microbiology

In 2010, Clinical and Laboratory Standards Institute modified the breakpoints for cephalosporins and established that it was no more necessary to systematically search for extended-spectrum beta-lactamases (ESBL), or to modify the interpretation criteria. Implementation of these changes is controversial in Argentine, due to its local epidemiological context, which shows a strong presence of CTX-M type enzymes.The aim of this study was to evaluate the in vitro response to ceftazidime (CAZ) and cefepime (FEP) against enterobacteria carrying different beta-lactam resistance markers (CTX-M or CMY-2) which may lead to a dissociated resistance phenotype to third generation cephalosporins (DRP-TGC).Five isolates which displayed DRP-TGC (all of them cefotaxime R and CAZ S) were included: C1: Escherichia coli carrying CMY-2; I9: Proteus mirabilis carrying of CMY-2; N1: E. coli carrying CTX-M-2; N8: E. coli carrying CTX-M-14 and C13: P. mirabilis carrying CTX-M-2. Time-kill curves of CAZ and FEP were performed using concentrations at 2xMIC and 4xMIC values, in Müeller-Hinton Broth (MHB). Colony forming units (CFU) counting were performed at 0, 3, 6 and 24 h of incubation. Time-kill curves were constructed by plotting log10 CFU/ml versus time. Bactericidal activity was defined as ≥3 log10 decrease in colony counting respect to the initial inoculum.A ≥3 log10 bacterial reduction was observed in CMY-2 producing isolates (C1, I9) within 3 and 6 h, at both concentrations of CAZ, but regrowth was observed at 24 h of incubation. FEP displayed bactericidal effect on these isolates. On the other hand, CAZ was bactericidal against CTX-M producing isolates (N1, N8, C13).When CTX-M-2 or CTX-M-14 were responsible of the DRP-TGC profile in both E. coli and P. mirabilis, CAZ presented an efficient in vitro bactericidal effect. Otherwise, when CMY-2 was involved in DPR-TGC, it did not act efficiently. However, in these isolates, FEP displayed bactericidal effect. Detection of the resistance mechanism involved in the DRP-TGC could constitute an important contribution when deciding clinical treatment, besides the decision only based on the susceptibility profile.