Early OXA-48-Producing <i>Enterobacterales</i> Isolates Recovered in a Spanish Hospital Reveal a Complex Introduction Dominated by Sequence Type 11 (ST11) and ST405 Klebsiella pneumoniae Clones

Abstract

Carbapenemase-producing <i>Enterobacterales</i> (CPE) have become an important public health concern. In our hospital, VIM enzymes were first detected in 2005, <i>Klebsiella pneumoniae</i> carbapenemase (KPC) enzymes in 2009, and OXA-48 enzymes in 2012. We assess the population biology of the first OXA-48-producing <i>Enterobacterales</i> isolates recovered in our hospital (2012 to 2013) where infections by other carbapenemases had been endemic for several years. Over a 21-month period, 71 isolates (61 <i>Klebsiella pneumoniae</i>, 5 <i>Escherichia coli</i>, 2 <i>Klebsiella aerogenes</i>, and 1 each of <i>Enterobacter cloacae</i>, <i>Klebsiella oxytoca</i>, and <i>Citrobacter amalonaticus</i>) recovered from clinical and surveillance specimens from 57 patients (22.8% nonhospitalized) were investigated for OXA-48-like-producing enzymes. Analyses for characterization and determination of the location of the <i>bla</i>_OXA-48 gene, plasmid transferability, sequence, and clonal relatedness were performed. Most of the isolates also coproduced CTX-M-15 (57/71, 80.3%) and/or VIM-1 (7/71, 9.8%). <i>K. pneumoniae</i> was predominantly identified as sequence type 11 (ST11) (63.4%) and ST405 (9.8%) and <i>E. coli</i> as ST540, ST1406, ST3163, and ST4301. The <i>bla</i>_OXA-48 gene was part of Tn<i>1999.2</i> located at the <i>tir</i> gene of plasmids (ca. ≥50 kb) of the IncL/M group, also carrying <i>bla</i>_VIM-1 and <i>bla</i>_CTX-M-15 genes. We selected one ST11 <i>K. pneumoniae</i> isolate for whole-genome sequencing in which we studied the plasmid containing the <i>bla</i>_OXA-48 gene. This plasmid was compared with indexed plasmids existing in NCBI database by the use of BRIG and MAUVE. Our data suggest a rapid spread of <i>bla</i>_OXA-48 genes between commonly isolated high-risk clones of <i>Enterobacterales</i> species, frequently associated with antibiotic resistance. Moreover, the emergence of the multiresistant ST11 <i>K. pneumoniae</i> clone among nonhospitalized patients emphasizes the difficulty of preventing its dissemination into the community.<b>IMPORTANCE</b> We present results of microbiological analysis of the first <i>Enterobacterales</i> isolates that were isolated in 2012 in our institution expressing OXA-48 carbapenemase. This enzyme confers resistance to carbapenems, an important group of antibiotics widely used in the hospitals. OXA-48 carbapenemase is currently present in many parts of the world, but it is found particularly frequently in the Mediterranean area. It was disseminated at the Ramón y Cajal Hospital and found to be associated with a particular <i>Klebsiella pneumoniae</i> strain, so-called high-risk clone ST11, which was previously found in our institution in association with other enzymes such as CTX-M-15, VIM-1, and KPC-3. This clone might have acquired a plasmid harboring the <i>bla</i>_OXA-48 gene. Our results point out the importance of local epidemiology in the dissemination and maintenance of multidrug-resistant bacteria.