Search

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

Objectives: Extended-spectrum β-lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. Methods: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-PhoenixTM confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. Results: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2.Conclusions: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.

Abstract Objectives: Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. Methods: Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). Results: The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. Conclusions: MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.