Antimicrob Agents Chemother. 2021 Oct 11:AAC0139721. doi: 10.1128/AAC.01397-21. Online ahead of print.
KBP-7072 is a novel third generation tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization-priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines. KBP-7072 demonstrated potent in vitro activity against gram-positive and gram-negative bacterial pathogens. KBP-7072 was active against Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L), methicillin-resistant S. aureus (MIC50/90, 0.06/0.12 mg/L), S. lugdunensis (MIC50/90, 0.03/0.03 mg/L), and other coagulase-negative staphylococci (MIC50/90, 0.06/0.25 mg/L). KBP-7072 was active against Enterococcus faecalis (MIC50/90, 0.03/0.06 mg/L) and vancomycin-susceptible and -nonsusceptible E. faecium (MIC50/90, 0.03/0.03 mg/L); Streptococcus pneumoniae (MIC50/90, ≤0.015/0.03 mg/L), including penicillin- and tetracycline-resistant strains; S. agalactiae (MIC50/90, 0.03/0.06 mg/L), including macrolide-resistant strains; S. pyogenes (MIC50/90, 0.03/0.03 mg/L); and viridans group streptococci, including S. anginosus group (MIC50/90, ≤0.015/0.03 mg/L) isolates. KBP-7072 inhibited 90.2% (MIC50/90, 0.25/2 mg/L) of all Enterobacterales isolates, including ESBL-phenotype strains, at ≤2 mg/L. KBP-7072 demonstrated potent activity against Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia isolates (MIC50/90 values, 0.5/1 mg/L), Haemophilus influenzae (MIC50/90, 0.12/0.25 mg/L; 100.0% inhibited at ≤0.25 mg/L), and Moraxella catarrhalis (MIC50/90, 0.06/0.06 mg/L). Based on MIC90 values, KBP-7072 in vitro activity was generally superior to the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur.