Enterobacteriaceae with dissociated resistance phenotype to third generation cephalosporins: in vitro response to ceftazidime and cefepime.

LIEBRENZ K; MARCHISIO MARTÍN; MENDEZ EMILCE; DI CONZA JOSÉ

Buenos Aires

Congreso; 18th International Congress on Infectius Diseases. XVIII Congreso SADI.; 2018

β-lactamases are the main mechanism of resistance to β-lactam antibiotics in gram-negative bacilli. Two relevant groups of these enzymes are the extended spectrum β-lactamases (ESBL) and plasmid mediated AmpC enzymes (pAmpC). Some isolates that produce these β-lactamases are susceptible or intermediate to 3rd or 4th generation. CLSI and EUCAST mentioned that they should be reported as tested and the presence or absence of an ESBL (or pAmpC) does not in itself influence the categorization of susceptibility.The aim of this study was to establish the in vitro response of different isolates of enterobacteria with dissociated resistance phenotype to third generation cephalosporins (TGC) against ceftazidime (CAZ) and cefepime (FEP).We studied 15 isolates (11 Escherichia coli, 3 Proteus mirabilis and 1 Klebsiella pneumoniae) resistant to TGC. Susceptibility profile was determined by disk diffusion method and Vitek 2 automated system. Five isolates (1 E. coli and 1 P. mirabilis with mechanism CMY-2 and 2 E. coli and 1 P. mirabilis with mechanism CTX-M) were studied by killing curves. They were performed in Mueller-Hinton Broth (MHB) with concentrations of FEP and CAZ of 2xMIC and 4xMIC, counting survivors at 0, 3, 6 and 24 h of incubation. Bactericidal activity of each antibiotic was defined as ≥ 3 log10 decrease in colony counting.All 5 isolates displayed dissociated resistance to TGC (all of them susceptible to CAZ and resistant to cefotaxime (CTX)). CTX MIC values for CTX-M producing isolates were 4 -64 µg/mL and CAZ MICs ranged from 1 to 4 µg/mL. CTX and CAZ MIC were equal to 4 µg/mL for both CMY-2 producers.Bactericidal activity of CAZ was observed on CTX-M producing isolates while CMY-2 producers regrowth after 24 h of incubation. Only bactericidal activity of FEP was observed in CMY-2 producers with both antimicrobial concentrations. When CTX-M resistance mechanism was responsible of dissociated phenotype to TGC, CAZ showed an efficient in vitro bactericidal effect. However, CAZ was not a bactericidal agent in those CMY-2 producing isolates but FEP displayed an excellent bactericidal activity against these last isolates. In conclusion, the detection of the resistance mechanism involved in the dissociated phenotype to TGC could constitute an important contribution when deciding clinical treatment.