In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections

• Published in: Antimicrobial agents and chemotherapy Vol. 61; no. 9
• Main Authors: McCurdy, S., Lawrence, L., Quintas, M., Woosley, L., Flamm, R., Tseng, C., Cammarata, S.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.09.2017
• Subjects: Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Asia; Double-Blind Method; Europe; Fluoroquinolones; Fluoroquinolones - pharmacology; Humans; Levofloxacin - pharmacology; Mechanisms of Resistance; Methicillin Resistance - drug effects; Microbial Sensitivity Tests - methods; Skin; Skin - microbiology; South America; Staphylococcal Skin Infections; Staphylococcal Skin Infections - drug therapy; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - drug effects; delafloxacin; ABSSSI; susceptibility; fluoroquinolone; Staphylococcus aureus
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/AAC.00772-17

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum in vitro activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible Staphylococcus aureus isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685 S. aureus isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints. S. aureus isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC 90 values against levofloxacin-nonsusceptible S. aureus , methicillin-resistant S. aureus (MRSA), and methicillin-susceptible S. aureus isolates were all 0.25 μg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR). S. aureus was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible S. aureus isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with S. aureus isolates with the S84L mutation in gyrA and the S80Y mutation in parC , the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by S. aureus isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.)