Short CommunicationDissemination of multiresistant Enterobacter cloacae isolates producing OXA-48 and CTX-M-15 in a Spanish hospital
Introduction
Enterobacter cloacae is an opportunistic pathogen frequently involved in nosocomial infections [1]. This enterobacterial species is intrinsically resistant to aminopenicillins, amoxicillin/clavulanic acid (AMC) and cephalosporins of early generations owing to a chromosomally encoded AmpC β-lactamase. Isolates overproducing AmpC are also resistant to broad-spectrum cephalosporins. Furthermore, E. cloacae has the ability to acquire additional resistance mechanisms, including plasmid-encoded extended-spectrum β-lactamases (ESBLs) and carbapenemases [1]. Phenotypic detection of ESBL production may be difficult since it can be masked by overexpression of AmpC. Some E. cloacae isolates may also exhibit permeability defects due to the absence of porins or porin mutations, further increasing the minimum inhibitory concentrations (MICs) of β-lactams and carbapenems, particularly ertapenem [1].
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 blaCTX-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 blaOXA-48 gene has been almost always located on a conjugative plasmid of ca. 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.
Section snippets
Setting, patients and bacterial isolates
‘Hospital Universitario Central de Asturias’ (HUCA) (Oviedo, Spain) is a 1100-bed university hospital providing care for a population of ca. 342,000 inhabitants in the Asturias region of northern Spain. During the 1-year period from June 2013 to June 2014, all E. cloacae isolates recovered at the hospital (n = 448) were analysed phenotypically for production of carbapenemases and ESBLs. A total of 21 multiresistant isolates, all recovered from different patients, produced a carbapenemase, an ESBL
Antimicrobial susceptibility and genetic basis for resistance to broad-spectrum cephalosporins and carbapenems
As shown in Table 2, 20 of the 21 E. cloacae isolates were resistant to cefotaxime and 11 were also resistant to cefepime. Moreover, 14 isolates displayed intermediate susceptibility or resistance to carbapenems. In addition to β-lactam antibiotics, all E. cloacae isolates were variably resistant to other antimicrobial groups, including quinolones (nalidixic acid and ciprofloxacin), aminoglycosides (gentamicin and tobramycin) and trimethoprim/sulfamethoxazole.
The blaCTX-M-15 gene was detected
Discussion
Enterobacter cloacae isolates producing OXA-48, CTX-M-15 or both β-lactamases emerged as important pathogens in HUCA, a general university hospital in northern Spain. In fact, they accounted for 4.7% (21/448) of the total E. cloacae isolates recovered over a 1-year period, although they were not previously reported in this region. Together with some sporadic isolates, two major clones (ST74 and ST66, falling in two different clusters according to PFGE analysis) are causing prolonged outbreaks
Conclusions
Intrahospital and interhospital dissemination of multiresistant E. cloacae isolates producing CTX-M-15, OXA-48 or both β-lactamases is a cause of concern due to the limited options remaining for the treatment of affected patients, most with critical underlying conditions. Interestingly, as observed for K. pneumoniae, emergence of both broad-spectrum resistance traits in single E. cloacae isolates corresponds to the transfer of genes having disseminated from community pathogens into nosocomial
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