A comparison of the efficacy and safety of intravenous followed by oral delafloxacin with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections: a phase 3, multinational, double-blind, randomized study.
Clin Infect Dis. 2018 Mar 06;:
Authors: O'Riordan W, McManus A, Teras J, Poromanski I, Cruz-Saldariagga M, Quintas M, Lawrence L, Liang S, Cammarata S, PROCEED Study Group
Background: Delafloxacin is an IV/oral anionic fluoroquinolone with activity against Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms. It is approved in the US for acute bacterial skin and skin structure infections caused by designated susceptible Gram-positive and Gram-negative organisms, and is in development for the treatment of community-acquired bacterial pneumonia.
Methods: A multicenter, randomized, double-blind trial of 850 adults with ABSSSI compared delafloxacin 300 mg IV Q12h for 3 days with a switch to 450 mg oral delafloxacin, to vancomycin 15 mg/kg IV with aztreonam for 5-14 days. The primary endpoint was objective response (OR) at 48-72 hours. Investigator‑assessed response based on resolution of signs and symptoms at Follow up (FU [Day 14±1]), and Late Follow up (LFU [Day 21- 28]) were secondary endpoints.
Results: In the intent-to-treat analysis set, the OR was 83.7% in the delafloxacin arm and 80.6% in the comparator arm. Investigator-assessed success was similar at FU (87.2% versus 84.4%) and LFU (83.5% versus 82.2%). Delafloxacin was comparable to vancomycin + aztreonam in eradication of MRSA at 96.0% vs 97.0% at FU. Frequency of treatment-emergent adverse events (TEAEs) between the groups was similar. TEAEs leading to study drug discontinuation was higher in the vancomycin + aztreonam group (1.2% vs 2.4%).
Conclusions: In ABSSSI patients, IV/oral delafloxacin monotherapy was noninferior to IV vancomycin + aztreonam combination therapy for both the OR and the investigator-assessed response at FU and LFU. Delafloxacin was well tolerated as monotherapy in treatment of ABSSSI.
PMID: 29518178 [PubMed - as supplied by publisher]