Extensively Drug-Resistant Pseudomonas aeruginosa Isolates Containing bla _VIM-2 and Elements of Salmonella Genomic Island 2: a New Genetic Resistance Determinant in Northeast Ohio

Abstract

k Carbapenems are a mainstay of treatment for infections caused by Pseudomonas aeruginosa. Carbapenem resistance mediated by metallo-␤-lactamases (MBLs) remains uncommon in the United States, despite the worldwide emergence of this group of enzymes. Between March 2012 and May 2013, we detected MBL-producing P. aeruginosa in a university-affiliated health care system in northeast Ohio. We examined the clinical characteristics and outcomes of patients, defined the resistance determinants and structure of the genetic element harboring the bla MBL gene through genome sequencing, and typed MBL-producing P. aeruginosa isolates using pulsed-field gel electrophoresis (PFGE), repetitive sequence-based PCR (rep-PCR), and multilocus sequence typing (MLST). Seven patients were affected that were hospitalized at three community hospitals, a long-term-care facility, and a tertiary care center; one of the patients died as a result of infection. Isolates belonged to sequence type 233 (ST233) and were extensively drug resistant (XDR), including resistance to all fluoroquinolones, aminoglycosides, and ␤-lactams; two isolates were nonsusceptible to colistin. The bla MBL gene was identified as bla VIM-2 contained within a class 1 integron (In559), similar to the cassette array previously detected in isolates from Norway, Russia, Taiwan, and Chicago, IL. Genomic sequencing and assembly revealed that In559 was part of a novel 35-kb region that also included a Tn501-like transposon and Salmonella genomic island 2 (SGI2)-homologous sequences. This analysis of XDR strains producing VIM-2 from northeast Ohio revealed a novel recombination event between Salmonella and P. aeruginosa, heralding a new antibiotic resistance threat in this region's health care system.

Intestinal Carriage of Carbapenemase-Producing Organisms: Current Status of Surveillance Methods

“…Bacteria other than lactose-fermenting Enterobacteriaceae can be detected with appropriate culture methods, and molecular screening tests will yield a positive result if a carbapenemase is present, regardless of the host organism. Inclusion of bacteria other than lactose fermenters in a screening program is important, as they can also transmit resistance elements to or within the Enterobacteriaceae, as has been previously suggested (75).…”

“…To illustrate, a recent surveillance study performed in northeastern Ohio uncovered a clinical isolate of Pseudomonas aeruginosa with bla VIM-2 in a class I integron that was proximal to a Salmonella genomic island (SGI), suggesting recombination between these two bacteria. A detailed analysis of this genetic locus showed multiple resistance and transposing elements that likely resulted in the successful dissemination of this isolate (75).…”

“…Per-observation estimates of sensitivity, specificity, and DOR for screening of rectal/perirectal swabs (75,133,135,144,145,149,150).…”

Tn 6249 , a New Tn 6162 Transposon Derivative Carrying a Double-Integron Platform and Involved with Acquisition of the bla VIM-1 Metallo-β-Lactamase Gene in Pseudomonas aeruginosa

“…However, few GIs associated with resistance genes have been described (18,(22)(23)(24), and only two of them have been fully sequenced (22,24). To the best of our knowledge, PA143/97 GI represents the third completely sequenced GI associated with resistance genes from a P. aeruginosa clinical isolate, providing new insight into the role of these elements in resistance dissemination.…”

Identification of VIM-2-Producing Pseudomonas aeruginosa from Tanzania Is Associated with Sequence Types 244 and 640 and the Location of bla VIM-2 in a TniC Integron

“…This observation indicates both the chromosomal and plasmid locations of bla VIM-2 . In addition to the identification of the integron structure in ST244 and ST640, this genetic structure has been identified in several other different genetic backgrounds of P. aeruginosa, such as ST233 (13,31), ST234 (27), ST235 (27,33), and ST1488 (10), with wide geographical distribution. This suggests that the integron is associated with mobile genetic structures facilitating horizontal transfer and dissemination, as previously suggested (29).…”