Characterization of VIM-4 Producing Clinical Pseudomonas aeruginosa Isolates from Western Algeria: Sequence Type and Class 1 Integron Description.

Objectives: Pseudomonas aeruginosa occupies a central position in nosocomial infections and remains a significant cause of morbidity and mortality. The aim of this study was to characterize carbapenem resistance mechanisms in P. aeruginosa isolates from clinical specimens collected at the University Hospital of Oran, western Algeria. Materials and Methods: The identification of 214 nonduplicated P. aeruginosa isolates (collected from January to December 2016) was confirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Thirteen antibiotics were tested using the disc diffusion method. Carbapenemase-encoding genes were detected with the GeneXpert system and multiplex polymerase chain reaction (PCR). Clonal relatedness was determined using multilocus sequence typing (MLST) and the seven housekeeping genes were further used for phylogenetic analysis of imipenem-resistant P. aeruginosa using concatenated gene fragments. The flanking regions of the blaVIM-4 gene were analyzed by whole-genome sequencing. Results: Eleven isolates (5.39%) were resistant to carbapenems. PCR amplification and sequencing showed that six of these isolates (2.94%) harbored the blaVIM-4 gene that was carried on a novel class 1 integron. MLST analysis assigned the tested isolates to seven different sequence types (STs), of which two were new (ST3349 and ST3350) and five were previously described (ST244, ST499, ST709, ST809, and ST1239). Conclusion: In this study, we reported P. aeruginosa isolates producing VIM-4 in an Algerian hospital. The blaVIM-4 is harbored in class 1 integron with a new arrangement of genes cassettes.

Assessment of the In Vitro Activities of Ceftolozane/Tazobactam and Ceftazidime/Avibactam in a Collection of Beta-Lactam-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Clinical Isolates at Montpellier University Hospital, France.

Objective: To assess in vitro ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) activity in beta-lactam-resistant Enterobacteriaceae and Pseudomonas aeruginosa clinical isolates from major carbapenem-using Departments at Montpellier University Hospital, France. Materials and Methods: We tested third-generation cephalosporin-resistant Enterobacteriaceae (by production of extended spectrum ß-lactamase or other mechanisms, mainly AmpC beta-lactamases) and ceftazidime- and/or carbapenem-resistant P. aeruginosa strains isolated from clinical samples of patients hospitalized from January 2017 to May 2017 and August 2016 to July 2017, respectively. We also included all OXA-48 beta-lactamase-producing Enterobacteriaceae strains isolated in the whole hospital from October 2015 to May 2017. We used the 2017 European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for minimal inhibitory concentration interpretation. Results: Among the 62 cephalosporin-resistant Enterobacteriaceae strains, 60 (97%) were susceptible to CZA and 34 (65%) to C/T. The two CZA-resistant Klebsiella pneumoniae isolates produced (i) NDM-carbapenemase and extended-spectrum beta-lactamase (ESBL) and (ii) ESBL CTXM-15 and OXA-1 associated with impermeability. Moreover, 31 of the 42 P. aeruginosa strains (74%) were susceptible to CZA and 37 (88%) to C/T. Finally, 26/27 (96%) of OXA-48 beta-lactamase-producing Enterobacteriaceae were susceptible to CZA and 8/27 (30%) to C/T. Conclusions: At our hospital, CZA and C/T offer a carbapenem-sparing alternative for resistant gram-negative pathogens and could be a salvage therapy for carbapenem-resistant pathogens.