In vitro antimicrobial susceptibility of clinical respiratory isolates to ceftazidime-avibactam and comparators (2016-2018)

Background: This antimicrobial surveillance study reports in vitro antimicrobial activity and susceptibility data for a panel of agents against respiratory isolates of Enterobacterales and Pseudomonas aeruginosa. Methods: Isolates from respiratory specimens were collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America between 2016 and 2018, as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Broth microdilution methodology was used to quantify minimum inhibitory concentrations, from which rates of susceptibility were determined using EUCAST breakpoints (version 10). Rates of subsets with genes encoding beta-lactamases (extended-spectrum beta-lactamases [ESBLs], serine carbapenemases and metallo-beta-lactamases [MBLs]) were also determined, as well as rates of multidrug-resistant (MDR) P. aeruginosa. Results: Among all respiratory Enterobacterales isolates, susceptibility to ceftazidime-avibactam, meropenem, colistin and amikacin was >= 94.4% in each region. For Enterobacterales isolates that were ESBL-positive or carbapenemase-positive/MBL-negative, ceftazidime-avibactam susceptibility was 93.6 and 98.9%, respectively. Fewer than 42.7% of MBL-positive Enterobacterales isolates were susceptible to any agents, except colistin (89.0% susceptible). Tigecycline susceptibility was >= 90.0% among Citrobacter koseri and Escherichia coli isolates, including all beta-lactamase-positive subsets. ESBL-positive Enterobacterales were more commonly identified in each region than isolates that were ESBL/carbapenemase-positive; carbapenemase-positive/MBL-negative; or MBL-positive. Among all respiratory P. aeruginosa isolates, the combined susceptibility rates (susceptible at standard dosing regimen plus susceptible at increased exposure) were highest to ceftazidime-avibactam, colistin and amikacin (>= 82.4% in each region). Susceptibility to colistin was >= 98.1% for all beta-lactamase-positive subsets of P. aeruginosa. The lowest rates of antimicrobial susceptibility were observed among MBL-positive isolates of P. aeruginosa (<= 56.6%), with the exception of colistin (100% susceptible). MDR P. aeruginosa were most frequently identified in each region (18.7-28.7%), compared with the subsets of ESBL-positive; carbapenemase-positive/MBL-negative; or MBL-positive isolates. Conclusions: Rates of susceptibility among the collections of respiratory Enterobacterales and P. aeruginosa isolates were highest to ceftazidime-avibactam, colistin and amikacin in each region. Tigecycline was active against all subsets of C. koseri and E. coli, and colistin was active against all subsets of P. aeruginosa. The findings of this study indicate the need for continued antimicrobial surveillance among respiratory Gram-negative pathogens, in particular those with genes encoding MBLs.

Automated summary

Across all regions, respiratory isolates of Enterobacterales and Pseudomonas aeruginosa showed highest susceptibility rates to ceftazidime-avibactam, colistin, and amikacin. Tigecycline demonstrated activity against all Citrobacter koseri and Escherichia coli subsets, while colistin was active against all subsets of P. aeruginosa.