Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis.
Mechanism of Action & Antibacterial Activity
Clindamycin, like erythromycin, inhibits protein synthesis by inter-fering with the formation of initiation complexes and with amino-acyl translocation reactions. The binding site for clindamycin on the 50S subunit of the bacterial ribosome is identical with that for erythromycin. Streptococci, staphylococci, and pneumococci are inhibited by clindamycin, 0.5–5 mcg/mL. Enterococci and gram-negative aerobic organisms are resistant. Bacteroides sp and other anaerobes, both gram-positive and gram-negative, are usually sus-ceptible. Resistance to clindamycin, which generally confers cross-resistance to macrolides, is due to (1) mutation of the ribosomal receptor site; (2) modification of the receptor by a constitutively expressed methylase (see section on erythromycin resistance, above); and (3) enzymatic inactivation of clindamycin. Gram-negative aero-bic species are intrinsically resistant because of poor permeability of the outer membrane.
Oral dosages of clindamycin, 0.15–0.3 g every 8 hours (10–20 mg/ kg/d for children), yield serum levels of 2–3 mcg/mL. When administered intravenously, 600 mg of clindamycin every 8 hours gives levels of 5–15 mcg/mL. The drug is about 90% protein-bound. Clindamycin penetrates well into most tissues, with brain and cerebrospinal fluid being important exceptions. It penetrates well into abscesses and is actively taken up and concentrated by phagocytic cells. Clindamycin is metabolized by the liver, and both active drug and active metabolites are excreted in bile and urine. The half-life is about 2.5 hours in normal individuals, increasing to 6 hours in patients with anuria. No dosage adjustment is required for renal failure.
Clindamycin is indicated for the treatment of skin and soft-tissue infections caused by streptococci and staphylococci. It is often active against community-acquired strains of methicillin-resistant S aureus, an increasingly common cause of skin and soft tissueinfections. Clindamycin is also indicated for treatment of anaerobic infections caused by Bacteroides sp and other anaerobes that often participate in mixed infections. Clindamycin, sometimes in com-bination with an aminoglycoside or cephalosporin, is used to treat penetrating wounds of the abdomen and the gut; infections origi-nating in the female genital tract, eg, septic abortion, pelvic abscesses, or pelvic inflammatory disease; and lung abscesses. Clindamycin is now recommended rather than erythromycin for prophylaxis of endocarditis in patients with valvular heart disease who are undergoing certain dental procedures and have significant penicillin allergies. Clindamycin plus primaquine is an effective alternative to trimethoprim-sulfamethoxazole for moderate to moderately severe Pneumocystis jiroveci pneumonia in AIDS patients. It is also used in combination with pyrimethamine for AIDS-related toxoplasmosis of the brain.
Common adverse effects are diarrhea, nausea, and skin rashes. Impaired liver function (with or without jaundice) and neutrope-nia sometimes occur. Administration of clindamycin is a risk fac-tor for diarrhea and colitis due to C difficile.