Abstract

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.

Disclosures

D. Shortridge, Melinta Therapeutics: Research Contractor, Research support. S. P. McCurdy, Melinta Therapeutics: Employee, Salary. 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.

Details

Title
2373. Evaluation of Delafloxacin Activity and Treatment Outcome for Phase 3 Acute Bacterial Skin and Skin Structure Infection Clinical Trial Anaerobic Isolates
Author
Shortridge, Dee 1 ; McCurdy, Sandra P 2 ; Rhomberg, Paul R 1 ; Huband, Michael D 1 ; Flamm, Robert K 1 

 JMI Laboratories, Inc., North Liberty, Iowa 
 Melinta Therapeutics, Lincolnshire, Illinois 
Pages
S706-S707
Publication year
2018
Publication date
Nov 2018
Publisher
Oxford University Press
e-ISSN
23288957
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3171023720
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.