In vitro activity of cefiderocol against Burkholderia cepacia complex and Burkholderia gladioli clinical isolates from cystic fib
Maria F Mojica, Elise T Zeiser, Scott A Becka, Lindsay J Caverly, John J Lipuma, Robert A Bonomo, Krisztina M Papp-WallaceAbstract
Background
Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are intrinsically multidrug-resistant pathogens that cause chronic pulmonary infections in individuals with cystic fibrosis (CF) and severe infections in other vulnerable populations. Therapeutic options remain limited as resistance to commonly used agents continues to emerge.
Objectives
To evaluate the in vitro activity of cefiderocol against a collection of Bcc and B. gladioli isolates from individuals with CF in the USA and to compare these findings with historical susceptibility data for 16 other antimicrobial agents.
Methods
A total of 150 clinical isolates representing multiple Bcc species and B. gladioli were tested. Cefiderocol MICs were determined using iron-depleted broth microdilution (ID-BMD) and iron-depleted agar dilution (ID-AD). Species-specific MIC distributions were assessed, and cefiderocol activity was compared with historical MIC data for 16 other antimicrobial agents previously tested against the same isolate panel. Mechanistic studies evaluated blaPenA expression and hydrolysis of cefiderocol by purified PenA1.
Results
Cefiderocol MIC50 and MIC90 values were 0.06 and 8 mg/L, and 0.03 and 8 mg/L, respectively, by both ID-BMD and ID-AD. Low MIC90 values were observed for Burkholderia cenocepacia, B. cepacia, B. gladioli, and most ‘other Bcc’ species, whereas elevated MIC90 values were detected for Burkholderia multivorans and Burkholderia vietnamiensis. Cefiderocol demonstrated the lowest MIC50 values when compared with historical data for 16 other agents; did not induce blaPen expression; and was not hydrolysed by purified PenA1.
Conclusions
Cefiderocol demonstrated broad in vitro activity against Bcc and B. gladioli isolates from individuals with CF and showed stability against key β-lactamase-mediated resistance mechanisms.