Clindamycin inhibits protein synthesis by binding to the 50S subunit of the ribosome and has a bacteriostatic effect at inhibitory concentrations. It is active against most Gram-positive aerobic bacteria, many anaerobes, and protozoa such as Plasmodium falciparum, P. vivax, Babesia, and Toxoplasma. Gram-negative bacteria are generally not susceptible. The antibacterial spectrum of clindamycin somewhat resembles that of the macrolide erythromycin. Clindamycin is available as clindamycin hydrochloride, clindamycin palmitate hydrochloride, and clindamycin phosphate. It can be administered orally, intramuscularly, or parenterally and is also available as vaginal ovule, topical solution, gel, lotion, foam, and cream. Trade names for clindamycin include Chlolincocin, Cleocin, Dalacin, Sobelin, Clindagel, ClindaMax, Clindesse, Clindets and Evoclin.

MECHANISM OF DRUG ACTION

Clindamycin inhibits bacterial protein synthesis by reversibly binding to the 23S rRNA nucleotides from the 50S subunit of the bacterial ribosome. It specifically interferes with substrate binding at the A and P sites in the peptidyltransferase cavity and thereby physically hinders the path of the growing peptide chain. In protozoa, clindamycin interferes with protein synthesis in the apicoplast, a parasite-specific organelle, and influences its mitochondria. Clindamycin is also known to have immunomodulating effects. It enhances chemotaxis and increases antibody production, opsonization, complement fixation, and phagocytosis by polymorphonuclear leukocytes. Whether clindamycin augments intracellular killing by neutrophils is uncertain. Intracellular killing of a clindamycin-resistant strain of S. aureus was modestly increased when the patient was treated with this drug; one possibility for this apparent synergy with intracellular killing mechanism would be 990 Other Antibiotics the increase in the intracellular concentration of clindamycin. 

Drug interactions

Although clindamycin appears to have a slight inhibitory effect upon the activities of CYP3A4, a study by Wynalda et al. (2003) suggests that clindamycin does not substantially alter the metabolism of coadministered drugs that are metabolized by this enzyme. Because the macrolides, streptogramins, ketolides, oxazolidone (linezolid), and chloramphenicol bind to the same subunit of the ribosome, these drugs should not be combined with clindamycin. Interactions with other drugs are mainly restricted to neuromuscular blocking agents. The effect of these agents can be enhanced by clindamycin and may lead to respiratory depression. Patients who concomitantly receive clindamycin and a neuromuscular blocking agent should therefore be closely monitored. Being a highly protein-bound drug, clindamycin may influence the serum free fraction of other drugs.

TOXICITY

The majority of side-effects of systemic clindamycin therapy are gastrointestinal; with topical application on the skin or in the vagina the dermatologic and vaginal side-effects predominate, respectively. The use of clindamycin may give rise to overgrowth of nonsusceptible organisms, particularly fungi. Clindamycin is absorbed following topical application and can result in systemic side-effects. Intravenously administered clindamycin can cause local thrombophlebitis. Intramuscular clindamycin is usually well tolerated, but has caused induration, sterile abscesses, and reversible increases in serum creatine kinase concentrations.

CLINICAL USES

Clindamycin is used to treat infections of bacterial and parasitic origin. Clindamycin is used for a wide range of clinical diseases and, although effective in severe bacterial infections, it is generally not regarded as the drug of first choice. Clindamycin is often used as alternative for beta-lactams in cases of hypersensitivity to penicillin. It can also be used to treat CA-MRSA infections, since most of these strains are susceptible. As a bacteriostatic drug, clindamycin is not considered to be suitable to treat severe infections as monotherapy, especially in immunocompromised hosts.