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Cardiac or Vascular Disease Not a Barrier to Delafloxacin For Treatment of Skin and Skin Structure Infections

Delafloxacin was found to be relatively safe and well tolerated in patients with acute bacterial skin and skin structure infections with past or present cardiac or vascular difficulties.

The analysis of the data from 2 multicenter, double-blind, double-dummy trials1,2 has provided some reassurance for patients with acute bacterial skin and skin structure infections (ABSSSIs) with past or present cardiac or vascular difficulties. The data from a poster presented at ID Week 2018 demonstrated the efficacy and safety of delafloxacin compared to the combination of vancomycin and aztreonam in such folks.

“This analysis demonstrated that delafloxacin intravenous (IV) and oral monotherapy was as effective as the combination of IV vancomycin/aztreonam in treating these complicated patients. Delafloxacin offers the flexibility for an early out-of-hospital transition with both the IV and oral forms and appears to be a consideration for treatment in these patients with convenient dosing,” said Sue Cammarata, MD, chief medical officer at Melinta (the marketer of delafloxacin), in an interview with Contagion®.

In the 2 trials, 1510 ABSSSI patients were randomized 1:1 to slightly differing dose regimens of delafloxacin alone (total n = 754) or the vancomycin-aztreonam combo (total n = 756) for up to 2 weeks. Aztreonam could be discontinued at the discretion of the investigator in the absence of gram-negative pathogens.

A total of 488 of the 1510 patients had cardiovascular issues. It was these patients that were evaluated for the study. Of the 488, 260 had received delafloxacin and 228 had received vancomycin-aztreonam. The patients were comparable in their response to treatment within the first 72 hours and in the subsequent follow-ups in terms of either the eradication of the pathogens of concern or improvement in the condition of the patients.

Key pathogens were comparably dispatched in the delafloxacin and vancomycin-aztreonam arms. These included Staphylococcus aureus (97.3% and 93.4% of isolates, respectively), methicillin-resistant S aureus (100% and 89.5%, in the same respective order), methicillin-sensitive S aureus (95.8% and 95.2%), S haemolyticus (100% in both arms), Pseudomonas aeruginosa (100% in both arms), Streptococcus agalactiae (100% and 85.7%), Strep pyogenes (100% in both arms), Escherichia coli (100% and 88.9%), Klebsiella pneumoniae (100% in both arms), and Enterococcus faecalis (100% and 87.5%).

Adverse events judged to be related to treatment were slightly more prevalent in the delafloxacin arm compared to the vancomycin-aztreonam arm (51.0% vs 46.1%). Treatment-related adverse events deemed to be due to the study drug were comparable in both arms (22.7% vs 22.4%), as were drug-related events that were moderate or severe (21.2% vs 22.4%). There were more discontinuations in the combination treatment arm, but they were not thought to be related to the treatment.

“Delafloxacin IV and oral monotherapy has been studied in 2 phase 3 ABSSSI trials with comparison to vancomycin/aztreonam intravenous combination therapy. Within those trials, 488 patients with serious skin infections had an underlying history of cardiac or vascular disease. These patients can be complicated to treat; they take many medications and have other underlying diseases like diabetes, kidney disease, heart failure, and hypertension. This makes the choice of antibiotic treatment complicated for the prescribing physician, [because of] the potential for drug-drug or drug-disease interactions,” explained Dr. Cammarata.

The results reinforce with the view of both the American Heart Association and American College of Cardiology Foundation, who recommend avoiding drugs that can exacerbate heart issues, particularly a prolonged QT interval, in hospitalized patients.3

The study arms were comparable in terms of age (about 58 years), sex (56%-58% male), race (86% White), and geography (about 45% from both Europe and the United States). Antibiotics had been used in the 2 weeks prior to enrollment for 26.9% and 28.5% of patients in the delafloxacin and vancomycin-aztreonam arms, respectively.

At baseline, infection was predominantly cellulitis/erysipelas (56.9% and 59.6% of patients in the delafloxacin and vancomycin-aztreonam arms, respectively), followed by wound infection (21.5% in both arms), and major cutaneous abscess (20.4% and 18.4%, respectively).

REFERENCES:

  1. Pullman J, Gardovskis J, Farley B, et al. Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: a phase 3, double-blind, randomized study. J Antimicrob. Chemother. 2017;72:3471-3480. doi: 10.1093/jac/dkx329.
  2. O’Riordan W, McManus A, et al. A comparison of the efficiacy and safety of intravenous followed by oral delafloxacin with vancomycin for the treatment of acute bacterial skin and skin structure infections: a phase 3, multinational, double-blind, randomized study. Clin. Inf. Dis. 2018;67:657-666.
  3. Drew B, Ackerman M, Funk, M et al. Prevention of toursade de points in hospital setting. Circulation 2010;121:1047-1060. doi: 10.1161/CIRCULATIONAHA.109.192704

DISCLOSURES

Godson Oguchi, MD: Melinta Therapeutics, Inc.: Investigator, Research support.

PRESENTATIONS

Poster Session: Skin and Skin Structure Infection

Godson Oguchi, MD

Midland Florida Clinical research Center LLC

Poster 2377. Outcomes in patients with history of cardiac or vascular disease (CV) during treatment of acute bacterial skin and skin structure infection (ABSSSI) with delafloxacin (DLX) vs vancomycin/aztreonam (VAN/AZ)

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.