Lincosamides

Lincosamides (clindamycin and the older lincomycin) are bacteriostatic protein synthesis inhibitors with excellent activity against Gram-positive cocci, many anaerobes, and certain protozoa. Clindamycin is the working agent. It combines good oral bioavailability with strong tissue and bone penetration and suppresses toxin production by streptococci and staphylococci. It also carries the highest risk of C. difficile infection of any antibacterial.

Mechanism. Binding to the 50S ribosomal subunit blocks peptide bond formation. Binding overlaps with macrolides, so the two are antagonistic when combined.

Pharmacokinetics. Oral bioavailability about 90 percent; half-life 2 to 3 hours; high levels in bone, abscess, skin and macrophages; poor CSF penetration; hepatic metabolism (CYP3A4), biliary and renal excretion.

Spectrum. Streptococci, MSSA, many community MRSA, Bacteroides and other anaerobes (resistance increasing in B. fragilis), Clostridium perfringens, Pneumocystis, Toxoplasma, Plasmodium, Babesia. Inactive against enterococci, Gram-negative aerobes and mycoplasma.

Resistance. Erm methylases cause inducible resistance, shown by erythromycin-induced clindamycin resistance (a positive D-test); clindamycin is avoided when the D-test is positive.

• Clindamycin: oral capsules, solution, IV, topical, vaginal.
• Lincomycin: rarely used; lower potency and more adverse effects.

Adult regimens (normal renal function).

• Skin and soft tissue infection, dental infection, bone and joint infection: 300 to 450 mg orally every 6 hours; IV 600 mg every 8 hours, up to 900 mg every 8 hours in severe infection (maximum 2.7 g daily IV; some regimens up to 4.8 g).
• Toxin suppression in necrotising fasciitis, streptococcal toxic shock and staphylococcal toxic shock: clindamycin 900 mg IV every 8 hours with a bactericidal beta-lactam (for example benzylpenicillin) and, in severe disease, intravenous immunoglobulin.
• Aspiration pneumonia or lung abscess with anaerobic infection: 600 mg IV every 8 hours.
• Severe malaria: with quinine, 10 mg/kg loading then 5 mg/kg every 8 hours for 7 days (or 300 mg every 6 hours in adults).
• Toxoplasmosis (sulphonamide intolerance): 600 mg every 6 hours orally or IV with pyrimethamine and folinic acid.
• Pneumocystis pneumonia (alternative): clindamycin 600 to 900 mg IV every 6 to 8 hours with primaquine 30 mg (base) daily.
• Bacterial vaginosis: 2 percent vaginal cream for 3 to 7 days, or oral 300 mg every 12 hours for 7 days.
• Children: 20 to 40 mg/kg daily in 3 or 4 divided doses; severe infection 40 mg/kg daily (maximum 2.7 g daily).

Selection. MRSA skin infection when susceptibility is confirmed; penicillin allergy in streptococcal and dental infection; toxin suppression adjunct; bone infection step-down. Not suitable for meningitis, endocarditis or bacteraemia caused by Gram-negative or enterococcal organisms. Avoid prolonged courses.

Contraindications. Hypersensitivity; prior clindamycin-associated colitis; use with caution in gastrointestinal disease.

Serious effects. C. difficile infection (can occur up to 2 months after treatment; boxed warning); severe diarrhoea; rash and severe cutaneous reactions; hepatotoxicity; neutropenia; neuromuscular blockade; oesophagitis from capsules taken without water.

Interactions. Neuromuscular blocking drugs (enhanced blockade); erythromycin (antagonism); rifampicin lowers clindamycin levels; CYP3A4 inhibitors raise levels.

Monitoring. Bowel habit throughout and for weeks after; liver tests and full blood count in prolonged courses; stop and test stool for toxin for new diarrhoea.

Special groups. Pregnancy: acceptable. Breastfeeding: acceptable, with monitoring for diarrhoea or blood in infant stool. Renal impairment: little change, but accumulation occurs in severe failure. Hepatic impairment: reduce dose in severe disease. Older adults: higher C. difficile risk.