In vitro activity of a novel aminomethylcycline antibacterial (KBP-7072), a third-generation tetracycline, against clinical isolates with molecularly characterized tetracycline resistance mechanisms

OBJECTIVES: This study evaluated the in vitro activity of KBP-7072 against 413 contemporary surveillance isolates, including subsets with known tetracycline resistance genes. MATERIALS: In total, 105 Klebsiella pneumoniae (51 tetracycline resistant), 103 Escherichia coli (52 tetracycline resistant), 103 Staphylococcus aureus (51 tetracycline resistant) and 102 Streptococcus pneumoniae (51 tetracycline resistant) isolates were included. These isolates were tested by broth microdilution using fresh media. CLSI/EUCAST breakpoints were applied, except for tigecycline and omadacycline, which used FDA criteria. RESULTS: KBP-7072 (MIC(50), 0.06 mg/L), tigecycline (MIC(50), 0.12 and 0.25 mg/L) and omadacycline (MIC(50), 0.12 and 0.5 mg/L) showed similar MIC(50)s for tetracycline-susceptible and -resistant S. aureus. Other tetracycline comparators had their MIC(50) increased 64- to 256-fold by tet. For S. pneumoniae, KBP-7072 (MIC(50/90), ≤0.015/0.03 mg/L) showed the lowest MICs, which remained unchanged for tetracycline-susceptible or -resistant isolates [mostly tet(M)]. Similar MICs were observed for omadacycline (MIC(50/90), 0.03–0.06/0.06 mg/L) and tigecycline (MIC(50/90), 0.03/0.03 mg/L) in the S. pneumoniae population. Tetracycline-susceptible and -resistant E. coli [94.2% tet(A)/tet(B)], KBP-7072 (MIC(90), 0.25 and 1 mg/L, respectively) and tigecycline (MIC(90), 0.25 and 0.5 mg/L) showed similar MIC(90)s. KBP-7072 (MIC(50/90), 0.25/0.5 mg/L) and tigecycline (MIC(50/90), 0.5/0.5 mg/L) had the lowest MIC for tetracycline-susceptible K. pneumoniae. The MIC for KBP-7072 (MIC(50/90), 1/4 mg/L) and tigecycline (MIC(50/90), 1/2 mg/L) increased 2- to 8-fold for tetracycline-resistant K. pneumoniae, which mostly produced Tet(A). CONCLUSIONS: KBP-7072 activity was minimally affected by the presence of acquired tetracycline genes.