In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from sub-Saharan Africa: ATLAS Global Surveillance Program 2017–2021

Abstract

To report the in vitro susceptibility of Enterobacterales (n=3905) and Pseudomonas aeruginosa (n=1,109) isolates, collected from patients in sub-Saharan Africa (four countries) in 2017-2021, to a panel of 10 antimicrobial agents with a focus on ceftazidime-avibactam activity against resistant phenotypes and β-lactamase carriers. MICs were determined by CLSI broth microdilution and interpreted using both 2022 CLSI and EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets using multiplex PCR assays. Among Enterobacterales, 96.2% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 0.5 µg/mL), including all serine carbapenemase-positive (n=127), 99.6% of ESBL-positive, carbapenemase-negative (n=730), 91.9% of multidrug resistant (MDR; n=1817), and 42.7% of DTR (difficult-to-treat resistance; n=171) isolates. Metallo-β-lactamase (MBL) genes were identified in most (n=136; 91.2%) ceftazidime-avibactam-resistant isolates (3.5% of all Enterobacterales isolates). Ceftazidime-avibactam percent susceptible values ranged from 99.5% (Klebsiella species other than Klebsiella pneumoniae) to 92.5% (K. pneumoniae) for the various Enterobacterial taxa examined. Greater than 90% of Enterobacterales isolates from each country (Cameroon, Ivory Coast, Nigeria, South Africa) were ceftazidime-avibactam-susceptible. Among P. aeruginosa, 88.9% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 16 µg/mL). Most (88.5%) MBL-negative, meropenem-resistant (n=78), 68.1% of MDR (n=385), and 19.2% of DTR isolates (n=99) were ceftazidime-avibactam-susceptible. MBL genes were identified in 43.1% of ceftazidime-avibactam-resistant isolates (n=53; 4.8% of all P. aeruginosa isolates). Country-specific ceftazidime-avibactam percent susceptible values for P. aeruginosa ranged from 94.1% (Cameroon) to 76.2% (Nigeria). Reference in vitro antimicrobial susceptibility testing demonstrated that most recent Enterobacterales (96%) and P. aeruginosa (89%) clinical isolates from four sub-Saharan African countries were ceftazidime-avibactam susceptible.