In vitro susceptibility of common bacterial pathogens causing respiratory tract infections in Canada to lefamulin, a new pleuromutilin

Abstract

Background: Community-acquired pneumonia (CAP) is a significant global health concern. Pathogens causing CAP demonstrate increasing resistance to commonly prescribed empiric treatments. Resistance in Streptococcus pneumoniae, the most prevalent bacterial cause of CAP, has been increasing worldwide, highlighting the need for improved antibacterial agents. Lefamulin, a novel pleuromutilin, is a recently approved therapeutic agent highly active against many lower respiratory tract pathogens. However, to date minimal data are available to describe the in vitro activity of lefamulin against bacterial isolates associated with CAP. Methods: Common bacterial causes of CAP obtained from both lower respiratory and blood specimen isolates cultured by hospital laboratories across Canada were submitted to the annual CANWARD study’s coordinating laboratory in Winnipeg, Canada, from January 2015 to October 2018. A total of 876 bacterial isolates were tested against lefamulin and comparator agents using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method, and minimum inhibitory concentrations (MICs) were interpreted using accepted breakpoints. Results: All S. pneumoniae isolates tested from both respiratory (n = 315) and blood specimens (n = 167) were susceptible to lefamulin (MIC ≤0.5 μg/mL), including isolates resistant to penicillins, clarithromycin, doxycycline, and trimethoprim–sulfamethoxazole. Lefamulin also inhibited 99.0% of Haemophilus influenzae isolates (regardless of β-lactamase production) (99 specimens; MIC ≤2 μg/mL) and 95.7% of methicillin-susceptible Staphylococcus aureus (MSSA) (MIC ≤0.25 μg/mL; 70 specimens) at their susceptible breakpoints. Conclusions: Lefamulin demonstrated potent in vitro activity against all respiratory isolates tested and may represent a significant advancement in empiric treatment options for CAP.