Pseudomembraneous colitis lincomycin

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). 

Pseudomembranous colitis was known before the introduction of antimicrobial agents and can still occur without previous antibiotic use, for example after antineoplastic chemotherapy (125) or even spontaneously. However, the number of cases has increased dramatically since antibiotics began to be used (126). Patients treated with lincomycin or clindamycin, cephalosporins, penicillinase-resistant penicillins, or combinations of several antibiotics... 

Although the first antibiotics reported to cause pseudomembranous colitis were lincomycin and clindamycin, the disease was later described with all other antimicrobial drugs, even topically applied (149). Vancomycin (150) and metronidazole (151), which may be used as specific treatments, have also been implicated. 

The most prominent adverse reaction of the lincosamides is diarrhea, which varies from mildly loose bowel movements to life-threatening pseudomembranous colitis (see monograph on Beta-lactam antibiotics). Almost all antimicrobial drugs have been associated with severe diarrhea and colitis however, lincomycin and clindamycin have been particularly incriminated. The incidence of clindamycin-induced diarrhea in hospital is 23%. Diarrhea resolves promptly after withdrawal in most cases. It seems to be dose-related and may result from a direct action on the intestinal mucosa. Severe colitis due to C. difficile is not dose-related and occurs in 0.01-10% of recipients. Clustering of cases in time and place suggests the possibility of cross-infection. Even low doses of clindamycin, in some cases after topical administration, can cause marked alterations in several intestinal functions related to bowel flora (23). There was reduced susceptibility of C. difficile to clindamycin in 80% of French isolates in 1997 (24). Lincomycin was among the antibiotics that were most often associated with the development of antibiotic-associated diarrhea in a Turkish study of 154 patients other associated antibiotics were azithromycin and ampicillin (25). 

Superinfection with resistant strains of Pseudomonas, Proteus, or staphylococci has been observed with lincosamides. Suppression of Bacteroides in the intestinal flora may be related to the prohferation of C. difficile, which is important in causing pseudomembranous colitis. Excessive growth of Candida on the skin occurred when lincomycin was applied topically (6). 

Lincomycin has generally been replaced by Clindamycin (Cleocin) because there are significant occurrences of pseudomembranous colitis in patients who use lincomycins. Clindamycin is a semisynthetic derivative of lincomycin that is safer and more effective than lincomycin. 

Lincomycin is a natural product isolated from fermentations of Streptomyces lincolnensis var. lincolnensis. It is active against Gram-positive organisms, including some anaerobes. It is indicated for the treatment of serious infections caused by sensitive strains of streptococci, pneumococci, and staphylococci. It generally is reserved for patients who are allergic to penicillin because of the increased risk of pseudomembranous colitis (described below). It also serves as the starting material for the synthesis of clindamycin (by a Sn-2 reaction that inverts the R stereochemistry of the C-7 hydroxyl to a C-7 S-chloride). 

The use of lincomycin is avoided because there is a significant occurrence of pseudomembranous colitis. Clindamycin is the dmg of choice because it is safer and more effective than lincomycin. 

However, note that marked diarrhoea is an indication that lincomycin or clindamycin should be stopped immediately. This is because it may be a sign of pseudomembranous colitis, which can be fatal. 

An important advantage of the lincomycins is their very low toxicity to the liver, the bone marrow, and the kidneys. Therefore, only a few adverse reactions are known. Diarrhea and severe pseudomembranous colitis have been observed after oral or parenteral treatment with either of the lincomycins. Retrospective as well as prospective studies have shown inconclusive results regarding the incidence of colitis (PiTMANN et al. 1974 Basler 1976). Clostridium difficile has been identified as the most probable cause of this intestinal side effect (reviewed by Manten 1979). 

Pirila V, Pirila L (1966) Sensitization to the neomycin group of antibiotics patterns of crosssensitivity as a function of polyvalent sensitization to different portions of the neomycin molecule. Acta Derm Venereol (Stockh) 46 489-496 Pirila V, Rouhunkoski S (1960) On cross-sensitization between neomycin, bacitracin, kana-mycin, and framycetin. Dermatologica 121 335-342 Pitmann FE, Pittman JC, Humphrey CD (1974) Lincomycin and pseudomembranous colitis. Lancet 1 451-452... 

The lincomycins, ie. lincomycin and its semisynthetic analogue clindamycin (7-chlorohncomycin), used to be fairly popular antibiotics as alternative drugs for penicillin, especially in known or presumed cases of penicillin allergy or resistance to this antibiotic. Since it has been observed that oral or parenteral administration of both lincomycin and clindamycin may cause fulminating diarrhoea as a sequel to pseudomembranous colitis, their popularity has considerably decreased. 

The mechanism for the occasionally serious side effects of the lincomycins has not as yet been fully clarified. Electron microscopic studies of pseudomembranes from patients treated with clindamycin have revealed numerous particles with the ultrastruc-tural characteristics of virus. The suggestion has therefore been advanced that lincomycin-associated colitis may be a viral condition (54 ). However, also other mechanisms have been suggested. One of these is that fibrin microthrombi are present in rectal biopsies, suggesting that it is possible that capillary... 

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