Emergence of Oxacillinase-Mediated Resistance to Imipenem inKlebsiella pneumoniae

Abstract

Klebsiella pneumoniae strain 11978 was isolated in Turkey in 2001 and was found to be resistant to all ␤-lactams, including carbapenems. Cloning and expression in Escherichia coli identified five ␤-lactamases, including two novel oxacillinases. The ␤-lactamase OXA-48 hydrolyzed imipenem at a high level and was remotely related (less than 46% amino acid identity) to the other oxacillinases. It hydrolyzed penicillins and imipenem but not expanded-spectrum cephalosporins. The bla OXA-48 gene was plasmid encoded and not associated with an integron, in contrast to most of the oxacillinase genes. An insertion sequence, IS1999, was found immediately upstream of bla OXA-48 . Another plasmid that encoded a second oxacillinase gene, bla OXA-47 , located inside a class 1 integron was identified in K. pneumoniae 11978. OXA-47 had a narrow spectrum of hydrolysis activity and did not hydrolyze ceftazidime or imipenem, as is found for the ␤-lactamase (OXA-1) to which it is related. In addition, ␤-lactamases TEM-1 and SHV-2a were expressed from the same K. pneumoniae isolate. Analysis of the outer membrane proteins of this isolate revealed that it lacked a porin of ca. 36 kDa. Thus, the high-level resistance to ␤-lactams of this clinical isolate resulted from peculiar ␤-lactamases and modification of outer membrane proteins.

Detection of an Ambler class D OXA-48-type β-lactamase in a Klebsiella pneumoniae strain in The Netherlands

“…Carbapenemases can be metallo-b-lactamases (Ambler class B), Klebsiella pneumoniae carbapenemases or KPC (Ambler class A), or more rarely carbapenem-hydrolysing oxacillinases of the OXA-48-type (Ambler class D) (Poirel et al, 2007). The carbapenem-hydrolysing class D b-lactamase OXA-48 was first identified in a K. pneumoniae isolate from Turkey (Poirel et al, 2004). Since then, several other OXA-48-producing isolates of various enterobacterial species (Citrobacter freundii and Escherichia coli) have been reported, mainly from Turkey but also from other countries, including Belgium (Cuzon et al, 2008a), the UK (Livermore, 2009) and India (Bell et al, 2009).…”

Epidemiology of antimicrobial resistance in bloodstream infections

“…82 OXA-48-producing isolates were first described in and then spread from Turkey where frequent nosocomial outbreaks were reported. [101][102][103][104][105] These isolates have now been disseminated to many European countries. 82 OXA-48 producing K. pneumoniae strains have been reported in many Middle Eastern and African countries, but rarely from North and South Americas.…”

Retrospective identification of a previously undetected clinical case of OXA-48-producing K. pneumoniae and E. coli: the importance of adequate detection guidelines

“…In fact, another IncL/M plasmid pKPoxa-48N1 (accession number: KC575416.2) was also highly similar with our plasmid (99 % identity; coverage 98 %). The class D β-lactamase OXA-48 conferring decreased susceptibility to carbapenems was first identified in a K. pneumoniae isolate in Turkey [4]. Since then, multiple other OXA-48-producing isolates of various Enterobacteriaceae species have been reported.…”