The US Food and Drug Administration (FDA) recently approved delafloxacin (BAXDELA) for acute bacterial skin and skin structure infections in adults.
Antibiotic resistance has become a major clinical challenge in both the hospital and community setting with multidrug resistant pathogens becoming more common. Skin and skin structure infections account for over 7 million cases annually in the community with almost 2% of cases admitted to hospital.1 Staphylococcus aureus (S. aureus), both methicillin susceptible (MS) and resistant (MR), are the most causative species; however, Gram-negative species are emerging in certain patient types.2
Almost all antibiotics are written empirically so choices should include agents with an appropriate spectrum. The US Food and Drug Administration (FDA) recently approved delafloxacin (BAXDELA) for acute bacterial skin and skin structure infections in adults.3 This new fluoroquinolone is available in both tablet, 450 mg, and intravenous, 300 mg, formulations and can be dosed for 5-14 days twice daily.
In common with other fluoroquinolones delafloxacin carries label warnings for tendonitis, tendon rupture, peripheral neuropathy, central nervous system effects and avoidance of delafloxacin in myasthenia gravis patients. Unlike some other class members there are no issues with QTc interval or other cardiac events4 and phototoxicity5. Equally, the only drug-drug interaction of note is the usual chelation agents, antacids and sulcralfate. There is no interaction with CYP450 isoforms or a range of hepatic and renal transporters with exception of P-gp and BCRP inhibitors, the relevance of this is unknown.
Delafloxacin is unique among the approved quinolones in that its antibacterial activity is enhanced in acidic conditions6, an environment seen across many infected sites including abscesses, lung tissues, and abdominal fluids.7 Indeed, delafloxacin is > 8 times more potent than moxifloxacin against S. aureus at pH 5.5; however, at a higher pH the difference decreases. Delafloxacin demonstrated similar microbiological and clinical efficacy across both quinolone susceptible and resistant isolates of S. aureus in the Phase 3 clinical trials program, thus supporting prior in vitro and animal study data.8
The phase 3 trial program comprised 2 multi-national, randomized, comparative studies versus intravenous vancomycin and aztreonam. A total of 1510 patients were enrolled. Delafloxacin was given intravenously alone in one study, and IV to oral in the second trial. As per FDA guidance, clinical response based on decrease in size of lesion by 48-72 hours was the primary objective.
For each of the 2 pivotal trails delafloxacin demonstrated a non-inferior response to vancomycin & aztreonam, 78.2% and 83.7% compared to 80.9% and 80.6%, respectively. At the follow-up visit, day 14, the clinically evaluable populations showed non-inferiority at 96.7% and 96.0% versus 97.55% and 97.0% for delafloxacin and vancomycin/aztreonam respectively.3 Microbiological eradication by delafloxacin as a monotherapy was similar across S. aureus (MS & MR) and Gram-negative species as the combination comparator regimen.
From a tolerability perspective, delafloxacin showed a similar profile to the comparator with nausea, diarrhea, headache, transaminase elevations and vomiting being the most common events reported.3
The approval of delafloxacin, BAXDELA, provides clinicians with a new convenient option which covers the majority of bacterial species implicated in skin infections such abscesses, wounds and cellulitis including some of the challenging multidrug resistant variants.
Dr. Tillotson is an infectious disease/medical microbiologist with over 30 years of pharmaceutical industry experience in clinical development and medical affairs. He has worked for multinational companies and small biopharma on a range of antibiotics including ciprofloxacin, fidaxomicin, and most recently, solithromycin. Dr. Tillotson has also authored over 150 peer-reviewed publications.