EVOLUCIJA REZISTENCIJE NA BETA-LAKTAMSKE ANTIBIOTIKE U ENTEROBACTER SPP. U HRVATSKOJ

Irena Franolić-Kukina, Sanda Sardelić, Nataša Beader, Dijana Varda-Brkić, Nataša Firis, Marko Čačić, Dorotea Šijak, Sonja Frančula-Zaninović, Vesna Elveđi-Gašparović, Ivana Mareković, Amarela Lukić-Grlić, Mihaela Ajman, Branka Bedenić

Rezistencija na cefalosporine proširenog spektra u Enterobacter spp. nastaje zbog indukcije ili derepresije AmpC-β-laktamaze, produkcije β-laktamaza proširenog spektra (ESBL) ili karbapenemaza. Cilj istraživanja bio je utvrditi mehanizme rezistencije na β-laktamske antibiotike na kolekciji od 58 izolata prikupljenih metodom slučajnog odabira u tri klinička centra u Hrvatskoj i Kantonalnom zavodu za javno zdravstvo Zenica u Bosni i Hercegovini u razdoblju od 2008. do 2011. godine, kao i utvrditi evoluciju rezistencije na tu skupinu antibiotika tijekom perioda istraživanja. Pretpostavka je istraživanja da će izolati Enterobacter spp. rezistentni na ceftazidim pokazivati različite mehanizme rezistencije od inducibilne i dereprimirane AmpC-β-laktamaze do β-laktamaza proširenog spektra, a u kasnijim godinama i karbapenemaza. Očekivana je i razlika u fenotipu i mehanizmima rezistencije između različitih centara. Osjetljivost na antibiotike testirana je metodom dilucije u bujonu, a geni rezistencije testirani su PCR-om. Plazmidi su karakterizirani tipizacijom replikona PCR-om. Istraživanje je pokazalo dominaciju β-laktamaza proširenog spektra iz porodice CTX-M u kombinaciji s derepresijom AmpC-β-laktamaze kao dominantan mehanizam rezistencije na cefalosporine proširenog spektra. Plazmidi koji su kodirali ESBL pripadali su različitim inkompatibilnim grupama. U izolatima iz KBC-a Zagreb zapažena je u posljednjoj godini istraživanja (2010.) pojava prvih metalo-β-laktamaza iz VIM-serije, što pokazuje evoluciju rezistencije na cefalosporine proširenog spektra od dereprimiranih AmpC-β-laktamaza i ESBL-a na početku istraživanja do karbapenemaza na njegovu kraju.

Enterobacter spp. develops resistance to expanded-spectrum cephalosporins by induction or derepression of chromosomal AmpC β-lactamase, or production of extended-spectrum β-lactamases (ESBLs) or carbapenemases. The aim of the study was to analyze the mechanisms of resistance to expanded-spectrum cephalosporins and the evolution of resistance mechanism during the study period (2008–2011) on a collection of 58 randomly collected Enterobacter spp. strains from three hospital centers in Croatia and Bosnia and Herzegovina during 2008-2010. The antibiotic susceptibility was determined by broth microdilution method according to CLSI. Resistance genes were determined by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). The hypothesis of the study was that there will be multiple mechanisms of ceftazidime resistance involved, from inducible and derepressed AmpC β-lactamases to extended-spectrum β-lactamases and carbapenemases at the end of the study. The isolates from different centers were expected to express different phenotypes and mechanisms of resistance. The study showed the predominance of derepressed AmpC β-lactamases combined with ESBLs belonging to CTX-M family as a mechanism of resistance to expanded-spectrum cephalosporins. The emergency of MBLs was reported in the last year of the study in University Hospital Center Zagreb. The plasmids encoding ESBLs belonged to different incompatibility groups. This points out to the evolution of β-lactam resistance in Enterobacter spp. from derepressed AmpC β-lactamases and ESBL to carbapenemases.