Lincosamide Antibiotics

LINCOSAMIDE ANTIBIOTICS

Clindamycin

This potent lincosamide antibiotic is similar in mechanism of action (inhibits protein synthesis by binding to 50S ribosome) and spectrum of activity to erythromycin with which it exhibits partial cross resistance. Modification of the ribosomal binding site by constitutive methylase enzyme confirs resistance to both. It inhibits most gram-positive cocci (including penicillinase producing Staph., but not MRSA), C. diphtheriae, Nocardia, Actinomyces, Toxoplasma, but the distinctive feature is its high activity against a variety of anaerobes, especially Bact. fragilis. Aerobic gram-negative bacilli, spirochetes, Chlamydia, Mycoplasma and Rickettsia are not affected.

Oral absorption of clindamycin is good. It penetrates into most skeletal and soft tissues, but not in brain and CSF; accumulates in neutrophils and macrophages. It is largely metabolized and metabolites are excreted in urine and bile. The t½ is 3 hr.

Side effects are rashes, urticaria, abdominal pain, but the major problem is diarrhoea and pseudomembranous enterocolitis due to Clostridium difficile superinfection which is potentially fatal. The drug should be promptly stopped and metronidazole (alternatively vancomycin) given to treat it.

Because of potential toxicity, use of clindamycin is restricted to anaerobic and mixed infections, especially by Bact. fragilis causing abdominal, pelvic and lung abscesses. It is generally combined with an aminoglycoside or cephalosporin. Metronidazole and chloramphenicol are the alternatives to clindamycin for covering the anaerobes. Anaerobic streptococcal and Cl. perfringens infections and those involving bone and joints respond well. It has also been employed for prophylaxis of endocarditis in penicillin allergic patients with valvular defects who undergo dental surgery, as well as to prevent surgical site infection in colorectal/pelvic surgery.

In AIDS patients, it has been combined with pyrimethamine for toxoplasmosis and with primaquine for Pneumocystis jiroveci pneumonia. Topically it can be used for infected acne vulgaris.

Clindamycin, erythromycin and chloramphenicol can exhibit mutual antagonism, probably because their ribosomal binding sites are proximal; binding of one hinders access of the other to its target site. Clindamycin weakly potentiates neuromuscular blockers.

Dose: 150–300 mg QID oral; 200–600 mg i.v. 8 hourly; DALCAP 150 mg cap; CLINCIN 150, 300 mg cap; DALCIN 150, 300 mg cap, 300 mg/2 ml and 600 mg/ 4 ml inj.

Lincomycin

It is the forerunner of clindamycin; has similar antibacterial and toxic properties, but is less potent and produces a higher incidence of diarrhoea and colitis—deaths have occurred. Thus, it has been largely replaced by clindamycin. It is absorbed orally and excreted mainly in bile; plasma t½ 5 hrs.

Dose: 500 mg TDSQID oral; 600 mg i.m. or by i.v. infusion 6–12 hrly.

LINCOCIN 500 mg cap, 600 mg/2 ml inj; LYNX 250, 500 mg cap, 125 mg/5 ml syr, 300 mg/ml inj in 1, 2 ml amp.