Delafloxacin, Vancomcyin/Aztreonam Efficacy Similar in Gram-Negative ABSSSI

DLX is an anionic fluoroquinolone antibiotic for the treatment for ABSSSI
DLX is an anionic fluoroquinolone antibiotic for the treatment for ABSSSI

This article is written live from ID Week 2017 Annual Meeting in San Diego, CA. MPR will be reporting news on the latest findings from leading experts in infectious diseases. Check back for more news from IDWeek 2017.

SAN DIEGO—Delafloxacin (DLX) was similarly effective against gram-negative (GN) acute bacterial skin and skin structure infection (ABSSSI) pathogens as vancomycin/aztreonam (VAN/AZ), according to research reported at IDWeek 2017.

“IV and oral monotherapy DLX had outcomes comparable to IV VAN/AZ combination therapy for ABSSSI patients with Gram-negative infections with both objective response (decrease in lesion size ≥20%) at 48 to 72 hours after initiation of study drug, and investigator-assessed response rates of cure at the follow-up visit by Gram-negative pathogens (MITT and ME populations), ” reported Sue K. Cammarata, MD, of Melinta Therapeutics, Lincolnshire, IL, and coauthors. 

DLX is an anionic fluoroquinolone antibiotic recently approved for the treatment of ABSSSI. The authors analyzed outcomes for adults with GN ABSSSI from a pair of international, double-blind, Phase 3 ABSSSI trials.

Patients had been randomly assigned 1:1 to receive either intravenous/oral DLX monotherapy or VAN (15mg/kg) with AZ for 5 to 14 days. Endpoints included objective response 48–72 hours after treatment initiation and investigator-assessed outcome at follow-up (Day 14) and late follow-up (Day 21–28).

A total of 1,042 patients had pathogens detected at baseline, of which 197 had a GN isolate, in most cases, as part of mixed infection, the authors reported. Median digital erythema area at baseline was 284.2cm2 [and] 25% had cellulitis, 27% abscesses, and 47% wound infections, the researchers reported.

“The most common location was the lower extremities,” Dr. Cammarata and coauthors reported. “K. pneumoniae was the most frequent GN isolate. The MIC50, MIC90 and MIC range were 0.12, 0.25, 0.03–4µg/mL for K. pneumoniae; 0.12, 2, 0.03–>8µg/mL for E. cloacae; 0.06, 4, 0.008–4µg/mL for E. coli; and 0.25, 4, 0.12–>8µg/mL for P. aeruginosa.”

A total of 85.6% of patients with GN pathogens who received delafloxacin saw an objective response at 48–72 hours, with a 98.7% investigator-assessed success rate at follow-up and 97.3% at late follow-up. The microbiologic success at follow-up was 100% for K. pneumoniae (17 of 17 patients), E. coli (11/11), and P. aeruginosa (11/11), and 91.7% for E. cloacae (11/12).

The proportion of patients with at least 1 treatment-emergent AE (TEAE) was similar for DLX (45.1%) compared to VAN/AZ (47.7%), thee researchers reported. The most frequent TEAEs in the DLX group were mild to moderate gastrointestinal events, including nausea and diarrhea "but these did not lead to treatment discontinuation," added Dr. Cammarata. The incidence of AEs were similar between the treatment arms, with 96% of TEAEs reported as mild or moderate. 

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Reference:

O'Riordan W, Overcash S, Lawerence L, McCurdy SP, Tseng C, Cammarata SK. Outcomes with IV/oral Delafloxacin (DLX) Compared to Vancomycin/Aztreonam (VAN/AZ) in Treatment of Patients (pts) with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Gram-negative (GN) Pathogens. Poster presented at IDWeek; October 4–8, 2017; San Diego, CA. http://www.idweek.org.