Delafloxacin

Delafloxacin is a newer anionic fluoroquinolone licensed for acute bacterial skin and skin structure infection and community-acquired bacterial pneumonia, with stronger activity against MRSA and better performance in acidic environments than older members of the class. It is a reserve drug with little availability in East Africa.

Classification. Fluoroquinolone, newer generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV with balanced affinity; bactericidal.

Spectrum. MRSA, MSSA, streptococci, pneumococci, enterococci in part, Enterobacterales, Pseudomonas aeruginosa (variable), Haemophilus, Legionella, Mycoplasma and some anaerobes.

Pharmacokinetics. Oral bioavailability about 59%. Half-life 4 to 8 hours. Protein binding about 84%. Glucuronidation with excretion in urine and faeces.

Availability in East Africa is very limited.

Adults. - Acute bacterial skin and skin structure infection: 300 mg IV over 60 minutes every 12 hours, or 450 mg orally every 12 hours, for 5 to 14 days. Oral step-down after IV is allowed. - Community-acquired bacterial pneumonia: 300 mg IV every 12 hours or 450 mg orally every 12 hours for 5 to 10 days. - Kidney impairment: eGFR 15 to 29 mL/min IV dose 200 mg every 12 hours; oral dose unchanged; eGFR under 15 mL/min not advised.

Children. Not established.

Alternatives. Linezolid, doxycycline, clindamycin, levofloxacin, moxifloxacin, vancomycin.

Boxed-warning level risks. Tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, aggravation of myasthenia gravis.

Contraindications. Fluoroquinolone hypersensitivity.

Adverse effects. Nausea, diarrhoea, headache, raised transaminases, vomiting. Serious: tendon rupture, neuropathy, central nervous system effects, dysglycaemia, hypersensitivity, Clostridioides difficile infection, aortic aneurysm or dissection risk. QT prolongation is minimal.

Interactions. Cations reduce absorption (take delafloxacin 2 hours before or 6 hours after antacids, iron, zinc, sucralfate and multivitamins); corticosteroids (tendon risk); sulphonylureas and insulin; warfarin.

Common prescribing errors. Giving with antacids or iron, using it for simple infection when older drugs work, and using it in severe renal failure.

Special groups. - Pregnancy: avoid unless essential. Breastfeeding: avoid. - Older adults: monitor tendon, glucose and central nervous system effects. - Kidney impairment: eGFR 15 to 29 mL/min IV 200 mg every 12 hours, oral dose unchanged; eGFR under 15 mL/min not advised. - Liver impairment: no adjustment.

Preparation. Oral with or without food, separated from cations. IV: reconstitute and dilute in 0.9% sodium chloride or 5% glucose, and infuse over 60 minutes. Avoid IV use when eGFR is under 30 mL/min if the solubilising vehicle accumulates.

Baseline and monitoring. - Baseline: medication review, creatinine, glucose in diabetes, pregnancy status. - During treatment: tendon pain, paraesthesia, mood and glucose.

Stop rules. Stop for tendon pain, neuropathy, psychiatric disturbance, severe hypoglycaemia or severe rash.

Referral and escalation. Infectious diseases consultation for resistant infection and any off-label use.