Retapamulin

Retapamulin is a topical pleuromutilin antibiotic applied as a 1% ointment for impetigo and small secondarily infected skin lesions caused by Staphylococcus aureus (methicillin-susceptible) or Streptococcus pyogenes. It is an alternative where mupirocin or fusidic acid resistance is a concern. It is not systemic and is not used for MRSA infection.

Classification. Pleuromutilin (topical).

Mechanism. Binds the 50S ribosomal subunit at the peptidyl transferase centre and blocks protein synthesis and the formation of the 50S subunit; bacteriostatic at low concentrations and bactericidal at the concentrations reached on the skin.

Spectrum. Methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes and other beta-haemolytic streptococci. Activity against MRSA is limited and use is not advised in known or suspected MRSA. Little activity against Gram-negative bacteria. No cross-resistance with other classes of antibiotics at present.

Pharmacokinetics. Systemic absorption through skin is low (blood levels usually under the detection limit or very low), higher through damaged skin and in children under 2 years. Metabolised by the liver (CYP3A4); excretion is minimal in urine.

Topical use only. Maximum course 5 days.

Adults and children from 9 months of age.

• Impetigo and small secondarily infected traumatic skin lesions caused by susceptible Staphylococcus aureus or Streptococcus pyogenes: apply a thin layer of 1% ointment to the affected area twice daily (every 12 hours) for 5 days. The treated area may be covered with a sterile bandage or gauze.
• Treated area: up to about 100 cm2 in adults and up to 2% of body surface area in children, as the product label states.
• Response check: review at 2 to 3 days; if no clinical response after 3 to 4 days, send a swab and consider an oral agent.

Children under 9 months. Not established.

Alternatives. Mupirocin, fusidic acid (topical); oral flucloxacillin, cephalexin or clindamycin for extensive impetigo.

Contraindications. Hypersensitivity to retapamulin, other pleuromutilins or any component. Do not apply to mucosal surfaces, the eyes or inside the nose.

Adverse effects. Application-site irritation, itching, erythema, burning or pain, headache, nausea, diarrhoea and cough (infrequent). Serious (rare): allergic contact dermatitis, hypersensitivity reactions, overgrowth of non-susceptible organisms including Clostridioides difficile infection (very rare).

Interactions. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat) can raise systemic exposure; avoid use in children under 24 months who are taking such drugs, and use caution in older children and adults. Do not combine with other topical products on the same area.

Common prescribing errors. Use beyond 5 days, use on large areas or on mucosal surfaces, use in MRSA infection, and use with strong CYP3A4 inhibitors in infants.

Special groups. - Pregnancy: use only when the benefit outweighs the risk (very limited data). Breastfeeding: acceptable; do not apply to the breast or nipple where the infant could ingest it. - Older adults: usual use. - Kidney impairment: no adjustment. - Liver impairment: no adjustment for topical use. - Region: availability in East Africa is limited; mupirocin and fusidic acid are more often available. Cost limits wider use, and its use should be kept for impetigo where those drugs have failed or resistance is shown.

Administration. Wash hands, clean the lesion, and apply a thin layer with a clean applicator or gloved finger; wash hands afterwards. Keep away from the eyes and mouth. Do not use occlusive dressings. Keep the child from scratching the area.

Baseline and monitoring. - Baseline: lesion extent, MRSA history, skin integrity, interacting drugs in infants. - During treatment: review for response at 2 to 3 days; check for application-site reactions.

Stop rules. Stop for skin sensitisation or worsening, spreading infection, systemic features, or at completion of 5 days.

Referral and escalation. Refer for extensive impetigo, cellulitis, systemic features, recurrent infection and suspected MRSA.