Lincosamides

LINCOSAMIDES

Mechanism of Action

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the 50S ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States.

Absorption, Distribution, Metabolism, and Excretion

Food in the stomach does not interfere with the absorp-tion of either clindamycin or lincomycin. Peak serum levels can be obtained 1 hour after intravenous admin-istration of clindamycin, and approximately 90% of the antibiotic is protein bound.

Lincomycin and clindamycin penetrate most tissues well, including bone. Therefore, bone and joint infec-tions caused by susceptible organisms respond well to treatment with clindamycin. These drugs also concen-trate within phagocytic cells, which may offer a thera-peutic advantage. Lincomycin and clindamycin do not readily penetrate the normal or inflamed meninges. They do, however, pass readily through the placental barrier. Their half-life is 2 to 2.5 hours.

Both clindamycin and lincomycin are metabolized by the liver, and 90% of the inactivated drug is excreted in the urine. If renal function is impaired, the amount of drug excreted in the feces will be increased.

Clinical Uses

Clindamycin is highly active against staphylococci and streptococci other than enterococci. Also, clindamycin has significant antibacterial activity against S. pyogenes (group A strep). However, the adverse reaction of pseudomembranous colitis has limited its use to indi-viduals who are unable to tolerate other antibiotics and to the treatment of penicillin-resistant anaerobic bacte-rial infections. Clindamycin has shown excellent activity topically against Corynebacterium acnes in patients with recalcitrant cystic facial acne who cannot tolerate tetra-cyclines. Precautions should be given to all patients us-ing the topical preparations, since the development of colitis is possible.

Both clindamycin and choramphenicol have excel-lent activity against anaerobic bacteria but have poten-tially life-threatening adverse reactions and should not be used without good justification.

Adverse Effects

The major adverse reactions reported are hypersensi-tivity rashes and diarrhea. The rash is usually itchy, mor-billiform, and general. Gastrointestinal intolerance with abdominal pain, nausea, and vomiting occurs infre-quently. Hepatotoxicity and bone marrow suppression have been noted.

It is important to differentiate between gastroin-testinal irritation and pseudomembranous colitis. In its most extreme form, the colitis results in mucosal ulcer-ation and bleeding and infrequently may necessitate colectomy. On rare occasions it has been fatal.