Characterization of carbapenem-resistant and XDR Pseudomonas aeruginosa in Canada: results of the CANWARD 2007–16 study

Abstract

Objectives Carbapenem-resistant Pseudomonas aeruginosa are emerging worldwide with increasing reports of carbapenemase-producing isolates. Carbapenem-resistant isolates may also be XDR. This study characterized carbapenem-resistant and XDR P. aeruginosa isolated from patients receiving care at Canadian hospitals from 2007 to 2016. Methods Antimicrobial susceptibility testing was performed using CLSI broth microdilution methods. PCR was used to detect carbapenemases (GES, KPC, NDM, IMP, VIM, OXA-48) and other resistance markers; specific carbapenemase gene variants were identified by DNA sequencing. Genetic relatedness was assessed by MLST and PFGE. Results From 2007 to 2016, 3864 isolates of P. aeruginosa were collected; 466 (12.1%) isolates were carbapenem resistant. The prevalence of carbapenem-resistant P. aeruginosa reached a peak of 17.3% in 2014. Colistin (94% susceptible) and ceftolozane/tazobactam (92.5%) were the most active agents against carbapenem-resistant P. aeruginosa. XDR P. aeruginosa comprised 4.5% of isolates; they were found to be genetically diverse and remained susceptible to colistin and ceftolozane/tazobactam. Only 4.3% (n = 20) of carbapenem-resistant P. aeruginosa harboured a carbapenemase; most were blaGES-5 (35%, n = 7). Wide genetic diversity was observed among carbapenem-resistant P. aeruginosa with >200 different sequence types identified. Conclusions Although the prevalence of carbapenem-resistant P. aeruginosa in Canada spiked in 2014 and 2015, carbapenemase-producing P. aeruginosa remain rare with only 20 (4.3%) isolates identified over a 10 year period. Broad genetic diversity was observed among both carbapenem-resistant and XDR phenotypes of P. aeruginosa. Pan-drug-resistant P. aeruginosa have not yet been identified in Canada.

Evaluation of the EDTA-Modified Carbapenem Inactivation Method for Detecting Metallo-β-Lactamase-Producing Pseudomonas aeruginosa

“…Previously characterized as extended-spectrum ␤-lactamases, some GES variants have displayed carbapenemase activity, including GES-20 (20), which was found in the majority of the GES-positive isolates in our study. GES-type carbapenemases account for the most common carbapenemase detected in P. aeruginosa isolates from Canada, particularly GES-5 (8). GES carbapenemases have also been frequently reported in Mexico, with GES enzymes identified in Ͼ90% of imipenem-resistant P. aeruginosa FIG 2 Halo effect of alternative testing of GES isolates.…”

“…pneumoniae carbapenemase (KPC), other serine-␤-lactamase-producing subtypes (i.e., Guiana extended spectrum [GES]) are being isolated more frequently in North America, particularly in Canada and Mexico (7)(8)(9). Recently, GES-harboring P. aeruginosa isolates were reported in two unrelated patients from Texas (10).…”

The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria

“…Recently, GES-5 and GES-24 carbapenemases were isolated from P. aeruginosa from long-term care facilities in South Korea [225]. GES-5 was also detected in studies from Canada [226], Indonesia [227], Dubai [67], and Japan [228]. A variant of GES-5 called GES-18 was isolated from P. aeruginosa recovered from the endotracheal aspirate of an elderly patient hospitalized in Belgium [229].…”

Treatment Options for <em>K. pneumoniae</em>, <em>P. aeruginosa</em> and <em>A. baumannii</em> Co-resistant to Carbapenems, Aminoglycosides, Colistin and Tigecycline. An Approach Based on the Mechanisms of Resistance to Carbapenems

“…In contrast to K. pneumoniae and other Enterobacteriaceae that acquire carbapenem-resistance predominantly by horizontal gene transfer of carbapenemases, resistance in P. aeruginosa is predominantly mediated by chromosomal mutations resulting in loss or reduction of porin OprD, overexpression of the cephalosporinase AmpC and overexpression of efflux pumps [38][39][40]. For example, only about 20% of carbapenem-resistant P. aeruginosa in Europe [38] and 4.3% in Canada [41] produced carbapenemases, predominantly metallo-β-lactamases (specifically VIM and IMP). However, the prevalence of MBL among carbapenem-resistant P. aeruginosa is rising [38] and in some settings the majority (70-88%) of carbapenem-resistant P. aeruginosa isolates are MBL producers [30,31].…”

“…However, the prevalence of MBL among carbapenem-resistant P. aeruginosa is rising [38] and in some settings the majority (70-88%) of carbapenem-resistant P. aeruginosa isolates are MBL producers [30,31]. Furthermore, GES-type carbapenemases are increasingly being reported in P. aeruginosa [41][42][43][44].…”