Outbreak Caused by an Ertapenem-Resistant, CTX-M-15-Producing Klebsiella pneumoniae Sequence Type 101 Clone Carrying an OmpK36 Porin Variant

Abstract

Although numerous studies have documented outbreaks of carbapenem-resistant Klebsiella pneumoniae (CRKP) possessing various carbapenemases, reports on outbreaks due to CRKP possessing extended-spectrum ␤-lactamases (ESBLs) and/or AmpCs with porin lesions have been limited. Here, we describe an outbreak caused by an ertapenem-resistant, CTX-M-15-producing clonal K. pneumoniae strain expressing an OmpK36 porin variant. From May 2012 to November 2012, 37 ertapenem-resistant K. pneumoniae isolates phenotypically negative for carbapenemase production were recovered from 19 patients hospitalized in the intensive care unit of a Greek hospital. The isolates were either susceptible or intermediate to other carbapenems and resistant to all remaining ␤-lactams but cefotetan. Phenotypic and molecular analysis revealed the presence in all isolates of the bla CTX-M-15 gene on a conjugative 100-kb plasmid, disruption in the expression of the ompK35 gene, and the production of an Ompk36 porin variant. The index case was a patient admitted from another hospital. Active surveillance upon admission and on a weekly basis was immediately initiated; environmental samples were also periodically tested. Molecular typing showed that all clinical isolates as well as two ertapenem-resistant environmental K. pneumoniae isolates belonged to the same clonal type and were assigned to multilocus sequence typing (MLST) sequence type 101 (ST101). As all colonized/infected patients were hospitalized during overlapping periods, cross-infection was considered the main route for the dissemination of the outbreak strain. Despite reinforcement of infection control measures and active surveillance, the outbreak lasted approximately 7 months. Identification of hidden carriers upon admission and by screening on a weekly basis was found valuable for early recognition and subsequent successful management of the outbreak.

Dissemination of extensively drug-resistant and KPC-2 producing Klebsiella pneumoniae isolated from bloodstream infections

“…These strains were highly resistant to carbapenems, but only susceptible to polymyxin and tigecycline, which have been ultimately considered as the last-resort treatment for such infections. Previous research demonstrated that antimicrobial-resistant K. pneumoniae isolates could carry multiple resistance genes simultaneously [13,14]. In our study, a high prevalence of β-lactamase genes was observed.…”

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).…”

“…Beside several minor clones, three internationally disseminated CTX-M-15 producing K. pneumoniae clones, namely ST15, ST101 and ST147 were present in the Clinical Centre University of Pécs, of which ST15 and ST147 are considered to be epidemic clones in Hungary [6,[32][33][34][35][36].…”

In vitro emergence of carbapenem resistance in extended-spectrum β-lactamase-producing Klebsiella pneumoniae clinical isolates

“…Additionally, nosocomial outbreaks by carbapenem-resistant strains were recently documented in which resistance was not mediated by carbapenemases [13][14]. In conclusion, this study demonstrates the rapid acquisition of decreased carbapenem susceptibility in ESBL-producing K. pneumoniae clinical isolates.…”

“…Previous research indicates that ESBL expression in combination with the loss of porin expression can reduce susceptibility to carbapenems in clinical K. pneumoniae and E. coli isolates [10][11][12]. Whilst numerous outbreaks of carbapenem-resistant K. pneumoniae possessing various carbapenemases have been documented; an outbreak caused by an ertapenem-resistant, CTX-M-15-producing clonal K. pneumoniae strain expressing an OmpK36 porin variant was only recently described [13][14].…”