Background: Delafloxacin, a fluoroquinolone antibiotic with Gram-negative and Gram-positive activity including MRSA, was approved for treatment of ABSSSI. In a phase 3 ABSSSI trial, DLX was non-inferior to VAN/AZ in both objective and clinical response endpoints. Clinical signs and symptoms (S&S) and lesion size measurements also were evaluated in this trial.
Methods: A multicenter, double-blind trial of adults with ABSSSI patients randomized 1:1 to receive either DLX monotherapy 300mg q12h IV with switch to oral 450 mg q12h or vancomycin (VAN) 15 mg/kg (actual body weight) with aztreonam (AZ) for 5 14 days. AZ was discontinued once Gram-negative infection was excluded in the VAN arm. The presence or absence of clinical S&S were collected at each evaluation timepoint. Patients with complete resolution of S&S were classified as complete cures. Lesions were measured by digital planimetry. Patient-reported pain was recorded by numerical rating scale (NRS; 0=no pain, 10= worst pain). Assessments were completed at baseline, during and at end of treatment (EOT), at Follow-up (FU day 14) and Late Follow-up (LFU day 21-28).
Results: 850 patients were randomized in US, Europe, Asia and Latin America. 63% were male with mean age 51 yrs. 48% had cellulitis, 25% abscesses, 26% wound and 1% burn infections. Baseline erythema and induration were reported in 100% and 93% of patients, respectively. Mean area of erythema and induration at baseline was 353 and 138 cm2 respectively. Most common locations for lesions were lower extremities (56%) and upper extremities (24 %). S. aureus was the most common isolate. Mean days of treatment was 7 days in either group. DLX and VAN/AZ patients had comparable impact on S&S with complete resolution in 42% vs 45 % at EOT, and 58% vs 60% at FU, and 68% vs 71% at LFU respectively. DLX was comparable to VAN/AZ in percent reduction in erythema over time (figure). There was a mean reduction of 58% vs 53% at 48-72 h, 90% vs 87% at EOT, and 98% vs 97% at LFU for DLX and VAN/AZ respectively (figure). Baseline mean pain scores were 7/10 with scores of ~1/10 at EOT and ~0.5/10 at FU for both treatment groups.
Melinta Therapeutics, Inc.:
L. Lawrence, Melinta Therapeutics, Inc.: Employee and Shareholder , Salary .
M. Quintas, Melinta Therapeutics, Inc.: Employee and Shareholder , Salary .
C. Tseng, Melinta Therapeutics, Inc.: Consultant and Research Contractor , Consulting fee .
S. K. Cammarata, Melinta Therapeutics, Inc.: Employee and Shareholder , Salary .