Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011

Abstract

OXA-48 beta-lactamase producers are emerging as an important threat mostly in the Mediterranean area. We report here the molecular epidemiology of a collection of OXA-48 beta-lactamase-positive enterobacterial isolates (n=107) recovered from European and north-African countries between January 2001 and December 2011. This collection included 67 Klebsiella pneumoniae, 24 Escherichia coli and 10 Enterobacter cloacae. Using the EUCAST breakpoints, ninety-eight isolates (91.6%) were of intermediate susceptibility or resistant to ertapenem, whereas 66% remained susceptible to imipenem. Seventy-five per cent of the isolates co-produced an extended-spectrum beta-lactamase, most frequently CTX-M-15 (77.5%). Susceptibility testing to non-beta-lactam antibiotics showed that colistin, tigecycline, amikacin, and fosfomycin remain active against most of the isolates. Multilocus sequence typing indicated that the most common sequence types (ST) were ST101 and ST38 for K. pneumoniae and E. coli, respectively. The blaOXA-48 gene was located on a 62 kb IncL/M plasmid in 92.5% of the isolates, indicating that a single plasmid was mainly responsible for the spread of that gene. In addition, this study identified multiple cases of importation of OXA-48 beta-lactamase producers at least in Europe, and spread of OXA-48 beta-lactamase producers giving rise to an endemic situation, at least in France.

Identification and characterization of CTX-M-15 producing Klebsiella pneumoniae clone ST101 in a Hungarian university teaching hospital

“…This sequence type was associated with various β-lactam resistance mechanisms in different parts of the world: CTX-M-15 production in France, Greece and Italy; SHV-12 production in the Czech Republic; OXA-48 production in Spain, Libya, France, Tunisia, Morocco, Switzerland and South Africa; KPC-2 production in Italy and Spain [32,[35][36][37][38][39][40][41][42]. In our institution the presence of CTX-M-15 producing ST101 seemed to be restricted both timely and spatially, as the majority of the isolates originated from a single department with a decreasing incidence ( Tables II and III).…”

Dissemination of multiresistant Enterobacter cloacae isolates producing OXA-48 and CTX-M-15 in a Spanish hospital

“…Transposon Tn1999 (known to carry the bla OXA-48 gene) and plasmid-mediated quinolone resistance genes [qnrA, qnrB, qnrS and aac(6 )-Ib-cr] were searched by PCR amplification followed by sequencing of the obtained products [3,9]. Plasmid DNA was extracted by the Kado and Liu method [5] and was visualised by agarose gel electrophoresis.…”

“…62 kb assigned to the IncL/M group and has been identified only in enterobacterial species [5,6]. Both CTX-M-15 and OXA-48 have been detected in several enterobacterial species, being particularly frequent in Klebsiella pneumoniae, whilst they are relatively uncommon in E. cloacae [2,3]. Here we report the clinical and genetic features of 21 E. cloacae isolates producing CTX-M-15, OXA-48 or both, which were mainly recovered from critically ill patients, in a Spanish hospital during a 1-year period.…”

“…In members of the Enterobacteriaceae family, CTX-M-15 and OXA-48 are among the most common enzymes involved in resistance to broad-spectrum cephalosporins and carbapenems, respectively [2,3]. CTX-M-15 is a class A ESBL encoded by the bla CTX-M-15 gene, which has been identified in plasmids of varying size (85-200 kb) and structure, and often belonging to the FII incompatibility (Inc) group [4].…”

“…CTX-M-15 is a class A ESBL encoded by the bla CTX-M-15 gene, which has been identified in plasmids of varying size (85-200 kb) and structure, and often belonging to the FII incompatibility (Inc) group [4]. OXA-48 is an Ambler class D carbapenemase that confers resistance to penicillins and reduced susceptibility to carbapenems but does not significantly hydrolyse broad-spectrum cephalosporins [3]. The bla OXA-48 gene has been almost always located on a conjugative plasmid of ca.…”