Clindamycin

Clindamycin (rINN) (IPA: ) is a lincosamide antibiotic used in the treatment of infections caused by susceptible microorganisms. Clindamycin is a semisynthetic antibiotic derived from lincomycin by 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the lincomycin. Clindamycin is marketed under various trade names including Dalacin (Pfizer), Cleocin (Pfizer), and in a foam as Evoclin (Connetics) and Duac(Stiefel).

Indications
Clindamycin is used primarily to treat infections caused by susceptible anaerobic bacteria. Such infections might include infections of the respiratory tract, septicemia and peritonitis. In patients with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria as well. It is also used to treat bone infections caused by Staphylococcus aureus. Topical application of clindamycin phosphate can be used to treat moderate to severe acne.

It is most effective against infections involving the following types of organisms:
 * Aerobic gram-positive cocci, including some members of the Staphylococcus and Streptococcus (eg. pneumococcus) genera.
 * Anaerobic gram-negative bacilli, including some members of the Bacteroides and Fusobacterium genera.

Clindamycin is also used occasionally in cases of suspected toxic shock syndrome in combination with a bactericidal agent such as vancomycin. The rationale for this approach is a presumed synergy between the bactericidal antibiotic, which causes the death of the bacteria by breakdown of the cell membrane, and clindamycin, which inhibits toxin synthesis.

Clindamycin has been proven to decrease the risk of preterm births in women diagnosed with bacterial vaginosis during early pregnancy to about a third of the risk of untreated women (Lamont, 2005).

Recently, clindamycin has been found to be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (Daum, 2007).

Available forms
Clindamycin preparations for oral administration include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride). It is also available for topical administration, in gel form and in a foam delivery system (both containing clindamycin phosphate), primarily as a prescription acne treatment.

Adverse effects
Common adverse drug reactions (ADRs) associated with clindamycin therapy—found in over 1% of patients—include: diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps, rash, and/or itch. High intravenous doses may cause a metallic taste, and topical application may cause contact dermatitis (Rossi, 2006).

Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics. Overgrowth of Clostridium difficile, which is inherently resistant to clindamycin, results in the production of a toxin that causes a range of adverse effects, from diarrhea to colitis and toxic megacolon (Rossi, 2006).

Rarely—in less than 0.1% of patients—clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzymes and/or hepatotoxicity (Rossi, 2006).

Pharmacokinetics
Approximately 90% of an oral dose of clindamycin is absorbed from the gastrointestinal tract and it is widely distributed throughout the body, excluding the central nervous system. Adequate therapeutic concentrations can be achieved in bone. There is also active uptake into white blood cells, most importantly neutrophils. (Klempner and Styrt, 1981)

Clindamycin is extensively metabolised in the liver, with some metabolites being active, such as N-dimethyl clindamycin and clindamycin sulfoxide. The elimination half-life is 1.5 to 5 hours. Clindamycin is primarily eliminated by hepatic metabolism; after an intravenous dose of clindamycin phosphate, about 4.5% of the dose is excreted in urine as clindamycin and about 0.35% as the phosphate salt (Plaisance, 1989). The metabolites of clindamycin are excreted primarily in the urine (Klasco, 2006).

Mechanism of action
Clindamycin has a bacteriostatic effect. It interferes with bacterial protein synthesis, in a similar way to erythromycin and chloramphenicol, by binding to the 50S subunit of the bacterial ribosome. This causes antagonism if administered simultaneously and possible cross-resistance.

In cats
Clindamycin has been used successfully in treating cats that are displaying symptoms of toxoplasmosis. This disease rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats. Toxoplasmosis is contagious to humans, and therefore cat owners, particularly pregnant women, should take precautions to prevent the spread of the disease.