In Vitro Activity of Delafloxacin and Microbiological Response Against Fluoroquinolone Susceptible and Non-Susceptible S. aureus Isolates from two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) [PublishAheadOfPrint]

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad spectrum in vitro activity, including Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and percent microbiological response in subjects infected with fluoroquinolone susceptible and non-susceptible S. aureus isolates was determined from two global Phase 3 studies of delafloxacin versus vancomycin plus aztreonam in ABSSSI. Patients were enrolled in 23 countries predominately in the US but also Eastern Europe, South America and Asia. The microbiological intent-to-treat population (MITT) included 1042 patients from which 685 S. aureus isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, N. Liberty, IA). Comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Non-susceptibility to these antibiotics was determined using CLSI breakpoints. S. aureus isolates were 33.7% levofloxacin non-susceptible (FQ-NS). The delafloxacin MIC₉₀ values against levofloxacin non-susceptible S. aureus, MRSA and MSSA were all 0.25 μg/mL. Delafloxacin demonstrated high rates of microbiological response against FQ-NS isolates as well as isolates with documented mutations in the Quinolone Resistance Determining Region (QRDR). S. aureus were eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin non-susceptible S. aureus isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). 98.6% microbiological response rates were observed with delafloxacin treated subjects with S. aureus isolates with mutations in S84L in gyrA/S80Y in parC, the most commonly observed mutation in global phase 3 studies. The data suggest that delafloxacin could be a good treatment option for S. aureus ABSSSI isolates where high rates of ciprofloxacin and levofloxacin non-susceptibility are observed including MRSA.

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