Introduction
Delafloxacin is a broad-spectrum fluoroquinolone antibiotic approved by the FDA in 2017. It represents a newer generation of fluoroquinolones with enhanced activity against Gram-positive pathogens and maintained activity against many Gram-negative organisms. Unlike other fluoroquinolones, delafloxacin is an anionic molecule at physiological pH, which contributes to its unique pharmacokinetic properties and spectrum of activity.
Mechanism of Action
Delafloxacin exerts its bactericidal effects through inhibition of both DNA gyrase (topoisomerase II) and topoisomerase IV enzymes. This dual inhibition disrupts bacterial DNA replication, transcription, repair, and recombination processes. Its anionic character at physiological pH allows for enhanced intracellular accumulation in both acidic environments (such as abscesses) and within phagocytic cells, potentially improving efficacy against intracellular pathogens.
Indications
Delafloxacin is FDA-approved for:
- Acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of designated Gram-positive and Gram-negative microorganisms
- Community-acquired bacterial pneumonia (CABP) caused by susceptible microorganisms
Specific pathogens include Staphylococcus aureus (including MRSA), Streptococcus pyogenes, Streptococcus anginosus group, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and others.
Dosage and Administration
Standard dosing:- ABSSSI: 300 mg IV every 12 hours or 450 mg orally every 12 hours
- CABP: 300 mg IV every 12 hours or 450 mg orally every 12 hours
- IV formulation: Administer over 60 minutes
- Oral formulation: May be taken with or without food
- Renal impairment: No dosage adjustment required for mild to moderate impairment (CrCl ≥ 15 mL/min). Use not recommended in severe renal impairment (CrCl < 15 mL/min)
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required based on age alone
- Pediatric: Safety and effectiveness not established in patients under 18 years
Pharmacokinetics
Absorption: Oral bioavailability is approximately 58.8%. Food does not significantly affect absorption. Distribution: Volume of distribution is approximately 30-40 L. Protein binding is approximately 84%. Penetrates well into skin blister fluid and lung epithelial lining fluid. Metabolism: Minimally metabolized (<1%) via glucuronidation, UGT1A1, UGT1A3. Elimination: Primarily excreted unchanged in feces (∼50%) and urine (∼30%). Half-life is approximately 3-7 hours.Contraindications
- Known hypersensitivity to delafloxacin or other quinolones
- History of tendon disorders associated with quinolone use
Warnings and Precautions
Boxed Warning: Fluoroquinolones, including delafloxacin, are associated with disabling and potentially irreversible serious adverse reactions including:- Tendinitis and tendon rupture
- Peripheral neuropathy
- Central nervous system effects
- Exacerbation of myasthenia gravis
- Hypersensitivity reactions
- Clostridium difficile-associated diarrhea
- Prolongation of QT interval (monitor in at-risk patients)
- Photosensitivity reactions
- Development of drug-resistant bacteria
Drug Interactions
Significant interactions:- Multivalent cations (antacids containing aluminum, magnesium; sucralfate, dairy products, mineral supplements): Administer delafloxacin at least 2 hours before or 6 hours after these products
- Warfarin: Monitor INR closely (potential for increased anticoagulant effect)
- Drugs that prolong QT interval: Use with caution and monitor
- Corticosteroids: Increased risk of tendon rupture
Adverse Effects
Common adverse reactions (≥2%):- Nausea (8%)
- Diarrhea (6%)
- Headache (4%)
- Transaminase elevation (3%)
- Vomiting (2%)
- Tendon rupture
- Peripheral neuropathy
- CNS effects (dizziness, insomnia, anxiety)
- Hypersensitivity reactions
- Clostridium difficile-associated diarrhea
- Prolonged QT interval
- Photosensitivity
Monitoring Parameters
- Clinical response to therapy
- Signs and symptoms of superinfection
- Renal function (baseline and periodic in at-risk patients)
- Liver function tests (baseline and periodic)
- Signs of tendon inflammation or rupture
- Neurological symptoms
- ECG monitoring in patients with known QT prolongation or taking concomitant QT-prolonging drugs
- Blood glucose in diabetic patients (rare reports of dysglycemia with fluoroquinolones)
Patient Education
- Complete the full course of therapy even if symptoms improve
- Report any tendon pain, swelling, or inflammation immediately
- Report numbness, tingling, or burning sensations
- Report any signs of allergic reaction (rash, hives, swelling)
- Avoid excessive sun exposure and use sunscreen
- Stay well-hydrated during treatment
- Inform healthcare providers of all medications being taken
- Do not take antacids, vitamins, or minerals within 2 hours before or 6 hours after delafloxacin
- Contact healthcare provider immediately if severe diarrhea develops
References
1. FDA Prescribing Information: Baxdela (delafloxacin) 2. Hoover R, Hunt T, Benedict M, et al. Single and multiple-dose study to determine the safety, tolerability, and pharmacokinetics of delafloxacin in healthy subjects. Clin Ther. 2016;38(1):89-100. 3. Remy JM, Tow-Keogh CA, McConnell TS, et al. Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization. J Antimicrob Chemother. 2012;67(12):2814-2820. 4. McCurry S, et al. A Phase 3 study of delafloxacin compared with vancomycin plus aztreonam in acute bacterial skin and skin structure infections. Clin Infect Dis. 2018;66(5):657-663. 5. O'Riordan W, et al. A randomized, double-blind, phase 3 study comparing delafloxacin with moxifloxacin for the treatment of community-acquired bacterial pneumonia. J Antimicrob Chemother. 2018;73(4):1041-1049. 6. Flamm RK, et al. In vitro activity of delafloxacin against contemporary bacterial pathogens from the United States and Europe, 2014. Antimicrob Agents Chemother. 2016;60(10):6101-6108.