Background: Delafloxacin (DLX) is a broad-spectrum fluoroquinolone (FQ) antibacterial; approved in 2017 by the Food and Drug Administration for treatment of acute bacterial skin and skin structure infections (ABSSSIs). DLX is in clinical development for community-acquired bacterial pneumonia (CABP). In this study, in vitro susceptibility (S) for DLX and comparator agents for gram-negative (GN) and gram-positive (GP) anaerobic isolates from Phase 3 ABSSSI clinical trials were determined and compared with the microbiologic response for evaluable isolates.
Methods: A total of 84 anaerobic isolates were collected during Phase 3 ABSSSI clinical trials and 9 additional Bacteroides fragilis (BF) were collected as part of the 2017 SENTRY surveillance program. The isolates tested included 11 BF, 13 Clostridium perfringens (CP), and other species with <10 isolates (Table). Isolate identifications were confirmed by molecular methods. Susceptibility testing was performed according to CLSI agar dilution methodology (M11, 2012). Other antimicrobials tested included clindamycin (CD), metronidazole (MTZ), and moxifloxacin (MXF). In addition, the activity of DLX and MXF were compared at standard pH 7.0 and at pH 6.0.
Results: DLX had the lowest MIC50/90 values against both GP and GN species and was 32-fold more active than MXF for all organisms. For BF, DLX was 4- to 16-fold more active than the other comparators. For CP, DLX was 32- to 64-fold more active than the 3 comparators. When comparing the activity of DLX and MXF at pH 6 vs. pH 7, DLX had the same MIC50/90 values while MXF MIC50/90 values were 2-fold less active at the lower pH (Table 1). Of the 84 clinical trial isolates, 21 were recovered from subjects in the microbiologically evaluable at follow-up (MEFU) population. All of the subjects had a favorable microbiological response (presumed eradication) at FU.
Conclusion: DLX demonstrated potent in vitro antibacterial activity against anaerobic isolates tested, including BF and CP and was more active than MXF. For all isolates combined, DLX activity was unchanged at lower pH while MXF MIC values increased 2-fold. These data suggest that DLX activity remains potent at a lower pH common at sites of infection.
P. R. Rhomberg, Melinta Therapeutics: Research Contractor , Research support .
M. D. Huband, Melinta Therapeutics: Research Contractor , Research support .
R. K. Flamm, Melinta Therapeutics: Research Contractor , Research support .