Clindamycin toxicity

Employed as the hydrochloride and administered by dilute intravenous injection, vancomycin is indicated in potentially life-threatening infections that cannot be treated with other effective, less toxic, antibiotics. Oral vancomycin is the drug of choice in the treatment of antibiotic-induced pseudomembranous colitis associated with the administration of antibiotics such as clindamycin and lincomycin (section 9.3). 

Clindamycin Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit Bacteriostatic activity against susceptible bacteria Skin and soft tissue infections anaerobic infections Oral, IV hepatic clearance (half-life 2.5 h) dosed every 6-8 hours Toxicity Gastrointestinal upset, difficile colitis... 

Quinine sulfate is appropriate first-line therapy for uncomplicated falciparum malaria except when the infection was transmitted in an area without documented chloroquine-resistant malaria. Quinine is commonly used with a second drug (most often doxycycline or, in children, clindamycin) to shorten quinine s duration of use (usually to 3 days) and limit toxicity. Quinine is less effective than chloroquine against other human malarias and is more toxic. Therefore, it is not used to treat infections with these parasites. 

Pyrimethamine, in combination with sulfadiazine, is first-line therapy in the treatment of toxoplasmosis, including acute infection, congenital infection, and disease in immunocompromised patients. For immunocompromised patients, high-dose therapy is required followed by chronic suppressive therapy. Folinic acid is included to limit myelosuppression. Toxicity from the combination is usually due primarily to sulfadiazine. The replacement of sulfadiazine with clindamycin provides an effective alternative regimen. 

Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis. Lincomycin, although structurally distinct, resembles erythromycin in activity, but it is toxic and no longer used. 

Competitive albumin binding of drugs with high serum protein affinity can increase pharmacologically active unbound concentrations and enhance the metabolism of low clearance drugs. Acute verapamil toxicity with ceftriaxone and clindamycin may be explained by this mechanism (210). 

The direct toxicity of the lincosamides is relatively low (SED-7, 389) (6). The adverse effects of clindamycin may be well below 1%. In a tertiary care center, adverse reactions to chndamycin were reported in 0.47% of 3896 courses, and in half of these events an effect of other medications could not be excluded (7). However, chnda-mycin has not been given in as high doses as hncomycin. 

Since the lincosamides are eliminated by biliary excretion, toxicity would be expected in patients with liver disease. High doses of clindamycin may be hepatotoxic (34). Abnormal liver function tests during treatment with hn-comycin are rare, and only in patients who had taken large doses (over 4 g/day) for more than 3 weeks (6). In another series, intravenous lincomycin 4—18 g/day was not associated with renal or hepatic toxicity (SED-7, 388). 

Paquet P, Schaaf-Lafontaine N, Pierard GE. Toxic epidermal necrolysis following clindamycin treatment. Br J Dermatol 1995 132(4) 665-6. 

With increasing frequency, clindamycin in combination with pyrimethamine is been used as the replacement drug for sulfadiazine in the treatment of cerebral toxoplasmosis. Perhaps this new combination again may send sulfadiazine nephrotoxicity into "oblivion". Nevertheless, until this possibility occurs, primary care physicians should be aware that sulfadiazine can cause renal toxicity and that effective preventive measures are available. 

Vancomycin hydrochloride is always administered intravenously (never intramuscularly), either by slow injection or hy continuous infusion, for the treatment of systemic infections. In shott-term therapy, the toxic side reactions arc usually slight, hut continued u.sc may lead to impaired auditory acuity, renal damage, phlebitis, and rashes. Bccau.se it is nut assorted or signilicantly degraded in the gastrointc.stinal tract, vancomycin may he administered orally fur the treatment of staphylococcal enterocolitis and for pseudomembranous colitis associated with clindamycin therapy. Some conversion to aglucovancomycin likely (Kcurs in the low pH of the stomach. The latter retains about three-fourths of the activity of vancomycin. 

Gray, J. E., Weaver, R. N., Moran, J., Feenstra, E. S. The parenteral toxicity of clindamycin 2-phosphate in laboratory animals. Toxicol. Appl. Pharmacol. 1974, 27, 308-321. 

In soft tissue infection caused by group A Streptococcus, streptococcal toxic shock syndrome may occur. Although penicillin and cefazolin are efficacious, experimental models of group A streptococcal infection show clindamycin to be more effective than penicillin. ... 

Although the distribution, persistence, and toxicity of these halogenated compounds — such as the chlorinated grisans, chloramphenicol, 7-chlorotetracycline, and clindamycin are antibiotics — are subject to the same principles as those outlined in this book, this aspect has seldom been examined. One exception that may serve as an illustration is the debromination of naturally occurring bromophenols by bacteria under anaerobic conditions (King 1988). 

Chloramphenicol also causes a decrease in the therapeutic effect of clindamycin, erythromycin, or lincomycin. Chloramphenicol increases the drug serum levels of phenobarbital (Luminal), phenytoin (Dilantin), or warfarin (Coumadin) which can lead to toxicity. 

Kishore K, Raina A, Misra V, Jonas E. Acute verapamil toxicity in a patient with chronic toxicity possible interaction with ceftriaxone and clindamycin. Arm Pharmacother (1993) 27, 877-80,... 

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