Omadacycline

Omadacycline is an aminomethylcycline available orally and intravenously, licensed for community-acquired bacterial pneumonia and skin and skin structure infection. It is used off-label for nontuberculous mycobacterial infection.

Classification. Aminomethylcycline (synthetic tetracycline).

Mechanism. Binds the 30S ribosomal subunit and overcomes efflux and ribosomal protection resistance; bacteriostatic.

Spectrum. MRSA, MSSA, streptococci, pneumococci, vancomycin-susceptible and some resistant enterococci, Haemophilus, Moraxella, Legionella, Mycoplasma, Chlamydia, Mycobacterium abscessus and Mycobacterium avium complex (variable), and some ESBL Enterobacterales. Not active against Pseudomonas, Proteus or Providencia.

Pharmacokinetics. Oral bioavailability about 35%, markedly reduced by food and cations. Half-life about 16 to 17 hours. Protein binding about 20%. Eliminated mainly by faeces and 14% in urine.

Availability in East Africa is very limited.

Adults, community-acquired bacterial pneumonia. - IV: 200 mg on day 1 (as one infusion over 60 minutes, or 100 mg over 30 minutes twice), then 100 mg once daily. - Oral: 450 mg once daily on days 1 and 2, then 300 mg once daily. - Duration 5 to 10 days.

Adults, acute bacterial skin and skin structure infection. - IV: 200 mg on day 1, then 100 mg once daily. - Oral: 450 mg once daily on days 1 and 2, then 300 mg once daily. - Duration 7 to 14 days.

Off-label (specialist). Mycobacterium abscessus complex and other nontuberculous mycobacteria: 300 mg orally once daily, as part of a multidrug regimen.

Children. Not established.

Alternatives. Doxycycline, tigecycline, eravacycline, linezolid, macrolides.

Contraindications. Hypersensitivity to omadacycline or tetracyclines; pregnancy.

Adverse effects. Nausea, vomiting, infusion-site reactions, raised liver enzymes, insomnia, headache, hypertension. Serious: hepatotoxicity, anaphylaxis, Clostridioides difficile infection, tooth discolouration, photosensitivity, benign intracranial hypertension.

Interactions. Cations (aluminium, magnesium, calcium, iron, zinc, bismuth) markedly reduce absorption; warfarin (INR rise).

Common prescribing errors. Taking oral doses with food, dairy or antacids, and using it in pregnancy or young children.

Special groups. - Pregnancy: avoid (foetal tooth and bone effects). Breastfeeding: avoid. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: no adjustment.

Preparation. Oral: fast for at least 4 hours before the dose and take with water only; no food or drink (other than water) for 2 hours afterwards, and no dairy, antacids or iron for 4 hours. IV: reconstitute each 100 mg vial with 5 mL of 0.9% sodium chloride or 5% glucose, dilute to 100 mL and infuse over 30 or 60 minutes.

Baseline and monitoring. - Baseline: pregnancy test, liver tests, medication review. - During treatment: liver tests weekly in prolonged courses; blood pressure.

Stop rules. Stop for anaphylaxis, severe hepatotoxicity or severe skin reaction.

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