Determination of meropenem and imipenem minimum inhibitory concentrations for carbapenemase production Enterobacteriaceae

Antimikrobna rezistencija postaje jedan od glavnih javno-zdravstvenih problema u posljednjih nekoliko godina, a naročito zabrinjava pojava otpornosti enterobakterija na karbapeneme, posredovana enzimima, karbapenemazama. Cilj ovog istraživanja je izolatima enterobakterija koji proizvode karbapenemaze odrediti minimalne inhibitorne koncentracije (MIK-ove) imipenema i meropenema te ispitati je li vrijednost MIK-a povezana s vrstom karbapenemaze koju izolat proizvodi. U ovom istraživanju određene su vrijednosti MIK-a za 306 izolata enterobakterija iz cijele Hrvatske prikupljenih u Referentnom centru za praćenje rezistencije bakterija na antibiotike. Vrijednosti MIK-a su određivane metodom razrjeđenja u bujonu. Među prikupljenim enterobakterijama Klebsiella pneumoniae je bila zastupljena s 53%, Enterobacter cloacae 37%, a ostale enterobakterije su činile 10%. Identificirano je ukupno 75 izolata enterobakterija koje luče KPC karbapenemazu, 33 izolata koji luče metalo-β-laktamaze iz skupne NDM, 131 izolat koji luči metalo-β-laktamazu iz skupine VIM i 67 izolata koji luči OXA-48 karbapenemazu. Pokazalo se da je proizvodnja NDM i KPC enzima bila statistički značajno povezana s visokim vrijednostima MIK-a za meropenem dok su sojevi s OXA-48 pokazivali najveću osjetljivost na meropenem. Određivanje MIK-a i vrste karbapenemaze u kliničkih izolata je bitno jer se izolati s neznatno povišenim MIK-ovima još uvijek mogu liječiti tim antibioticima.The prevalence of carbapenem-resistant Gram-negative bacilli is on the rise worldwide, posing a major public health threat. Resistance is conferred by carbapenemases, which are beta-lactamases that can breakdown essentially all beta-lactams. The aim of this study was to determine minimal inhibitory concentrations (MIC values) of carbapenemase-producing enterobacteriaceae for imipenem and meropenem, and examine whether the value of MIC is associated with the type of carbapenemase that isolate products. In this study we determined MIC values of 306 isolates of enterobacteria gathered in the Croatian Reference Centre for Antibiotic Resistance. MIC values were determined by the method of broth dilution. Among collected enterobacteria Klebsiella pneumoniae was represented with 53%, Enterobacter cloacae 37%, and other enterobacteria constituted 10%. A total of 75 isolates of enterobacteria produced KPC carbapenemase, 33 isolates produced metallo-β-lactamase from the NDM group, 131 isolate produced metallo-β-lactamase from the VIM group and 67 isolates produced OXA-48 carbapenemases. It has been shown that the production of the enzyme KPC and NDM was significantly associated with high MIC values for meropenem while strains with OXA-48 showed the highest sensitivity to meropenem. Determination of MIC and types of carbapenemases in clinical isolates is important because it isolates the slightly elevated MIC can still be treated with these antibiotics