In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) When Tested against Contemporary Clinical Bacteria from a Global Surveillance Program [PublishAheadOfPrint]

Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in Phase 2 development for treatment of community-acquired bacterial pneumonia (CABP): A total of 4,739 non-duplicate isolates were selected from a 2014 global surveillance program from medical institutions located in 43 countries within the United States, Europe, Latin America, and Asia-Pacific. Nafithromycin and comparator agents were susceptibility tested by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC_50/90, 0.06/>2 μg/mL), including erythromycin-resistant strains exhibiting an inducible clindamycin-resistance phenotype (MIC_50/90, 0.06/0.06 μg/mL) and telithromycin-susceptible strains (MIC_50/90, 0.06/0.06 μg/mL), but exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC_50/90, >2/>2 μg/mL). Nafithromycin was very active (MIC_50/90, 0.015/0.06 μg/mL) against 1,911 Streptococcus pneumoniae, inhibiting all strains at MIC values ≤0.25 μg/mL. Telithromycin susceptibility was 99.9% against Streptococcus pneumoniae, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of S. pneumoniae were resistant to erythromycin and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606 Streptococcus pyogenes (MIC_50/90, 0.015/0.015 μg/mL), inhibiting 100.0% of isolates at ≤0.5 μg/mL, and MIC_50/90 values (0.015/0.015-0.03 μg/mL) were similar for each of the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable in vitro activity against 1,002 Haemophilus influenzae isolates and 504 Moraxaxella catarrhalis. Overall, nafithromycin showed potent in vitro activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for CABP.

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