Wide Dissemination of GES-Type Carbapenemases in Acinetobacter baumannii Isolates in Kuwait

Abstract

bAcinetobacter baumannii is an opportunistic pathogen that is an important source of nosocomial infections. Production of extended-spectrum ␤-lactamases (ESBLs) of the GES type in A. baumannii has been increasingly reported, and some of these GEStype enzymes possess some carbapenemase activity. Our aim was to analyze the resistance determinants and the clonal relationships of carbapenem-nonsusceptible A. baumannii clinical isolates recovered from hospitals in Kuwait. A total of 63 isolates were analyzed, and all were found to be positive for bla GES -type genes. One isolate harbored the bla GES-14 gene encoding an ESBL with significant carbapenemase activity, whereas the other isolates harbored the bla GES-11 ESBL gene. Thirty-three isolates coharbored the bla OXA-23 and bla GES-11 genes. Analyses of the genetic locations indicated that the bla GES-11/-14 genes were plasmid located. It is noteworthy that the bla OXA-23 and bla GES-11 genes were colocated onto a single plasmid. Nine different pulsotypes were observed among the 63 isolates. This study showed the emergence of GES-type ESBLs in A. baumannii in Kuwait, further suggesting that the Middle East region might be a reservoir for carbapenemase-producing A. baumannii. Acinetobacter baumannii is an opportunistic pathogen that is an important causative agent of nosocomial infections, such as pneumonia, septicemia, urinary tract infections, and wound infections (1). Multidrug-resistant (MDR) A. baumannii isolates are increasingly reported worldwide and are often a source of nosocomial infections. Treatment of infections due to this microorganism is becoming a serious clinical concern, since A. baumannii is very often resistant to multiple antibiotics (1). One of the main mechanisms of resistance to ␤-lactam molecules in this species is the production of ␤-lactamases (2). Resistance to carbapenems is mostly related to the production of carbapenem-hydrolyzing class D ␤-lactamases (CHDLs) and, to a lesser extent, of metallo-␤-lactamases (MBLs). Among these CHDLs, OXA-23 is the most commonly identified CHDL worldwide (2), and its corresponding gene is located on either a plasmid or a chromosome and at the origin of its acquisition is associated with the insertion sequence ISAba1 or ISAba4 (3). Although resistance to carbapenems is mostly related to the production of CHDLs that do not include broad-spectrum cephalosporins in their hydrolytic spectrum, resistance to broad-spectrum cephalosporin molecules in A. baumannii usually results from overexpression of the natural AmpCtype enzyme but also from the acquisition of extended-spectrum ␤-lactamases (ESBLs) (2). Those ESBLs may correspond to TEM or SHV derivatives but mostly correspond to Ambler class A ␤-lactamases of the VEB, PER, and GES types (2). ESBLs of the GES type are being reported increasingly in Gram-negative rods, including Pseudomonas aeruginosa, Enterobacter cloacae, and Klebsiella pneumoniae (4) and were recently reported in A. baumannii (5-7). While the hydrolysis profile of GES-1 is similar to that o...

Multidrug-resistant Acinetobacter baumannii strains carrying the blaOxA-23 and the blaGES-11 genes in a neonatology center in Tunisia

“…OXA-type carbapenemases have predominated in A. baumannii, especially worldwide outbreaks of OXA-23 [1]. Recently the GES-1-like carbapenemases have also been reported for A. baumannii [9,14,23,24,25].…”

“…Since then, several GES-1 mutants have been detected in A. baumannii, such as GES-12, GES-14, and GES-22 [9,14,22,23,24]. a CLA, Clavulanic acid (4 mg/ml); TZB, Tazobactam (4 mg/ml).…”

“…GES-11 b-lactamase possesses increased activity against aztreonam [14,23]. However the bla GES-11 -carrying transconjugant showed reduced susceptibilities to carbapenems, suggesting the presence of weak hydrolysis of carbapenems by this enzyme potentiated by the efflux overproduction in A. baumannii BM4547 [14,23].So, GES-11 may contribute to play a synergistic role toward resistance to carbapenems in A. baumannii, together with OXA-23 [14].Several studies reported the association between the bla GES and bla OxA-like gene, especially bla GES-11 and bla OxA-23 genes [14,23,24]. To our knowledge, however, carbapenem resistant A. baumannii isolate producing the carbapenem-hydrolyzing oxacillinase OXA-23 in association with the GES-11 class A b-lactamase in Tunisia have not been reported previously.…”

“…Plasmid analysis and AB-PBRT PCR showed that both plasmids (pAb453 and pAB537) were of ca. 90 Kb in size and belonged to the plasmid group Gr6 which has been shown to be highly prevalent in A. baumannii strains and was previously found to be associated with the bla OxA-23 , bla OxA-40 ,,bla OxA-58 CHDL genes and the bla GES-11/ GES-14 genes [2,14,24].…”

“…DNA in supernatant was used as a template under standard PCR procedure [9] with a series of different sets of primers. Detection of the known acquired CHDLs (bla OxA-23, bla , and bla OxA-58 ) [14], class A extended-spectrum b-lactamases (bla PER , bla VEB , and bla GES ) [14,15], MBL (bla IMP , bla VIM , bla SIM , bla NDM ) [16,17] and the intrinsic bla OxA-51-like gene was performed as previously described [14].…”