J Clin Pathol: first published as 10.1136/jcp.31.5.439 on 1 May 1978. Downloaded from Journal of Clinical Pathology, 1978, 31, 439-443 Effect of clindamycin and lincomycin therapy on faecal flora D. A. LEIGH AND K. SIMMONS From the Department ofMicrobiology, Wycombe General Hospital, High Wycombe, Buckinghamshire, UK SUMMARY Bacterial counts were carried out on the faeces of 160 patients receiving clindamycin or lincomycin treatment for bacterial infections. In all the patients the total bacteroides count was significantly reduced while strains ofEnterobacteriaciae, yeasts, and streptococci were corresponding- ly increased. Severe diarrhoea developed in 25 (16%) patients, but this could not be related to a change in faecal flora. Diarrhoea was most common when clindamycin was given prophylactically, women were more affected than men, and the incidence was highest in those aged over 60 years. No cases of pseudomembranous colitis were seen. Although clindamycin is a valuable antibiotic for treating established severe anaerobic bacterial infections it should be used cautiously in elderly patients. The clinical use of many antibiotics is associated colostomies. Of the 160 patients, 131 were receiving with changes in gastrointestinal function in some clindamycin (66 parenterally, eight orally, and 57 by patients. The incidence varies with the particular both routes) and 29 lincomycin (nine parenterally, antibiotic, and the nature may range from a slight six orally, and 14 by both routes). Other antibiotics, increase in bowel movements or less consistency of most commonly ampicillin or amoxycillin, were the faeces to severe watery diarrhoea with blood being received by 102 patients on clindamycin and http://jcp.bmj.com/ and mucus and possibly pseudomembranous colitis. 22 on lincomycin. Established bacterial infection The cause of the gastrointestinal dysfunction is not related to the gastrointestinal or genital tracts was clear. Many explanations such as a direct toxic present in 143 patients, usually confirmed at opera- effect of the antibiotic or its metabolites; the over- tion, and 17 patients received prophylactic treat- growth of certain pathogenic organisms such as ment: 61 of the infections were considered to be Staphylococcus aureus, Candida albicans, and Pseu- severe, 76 moderate, and six minimal. domonas aeruginosa; viruses; and toxins have been Specimens for bacteriological culture were collec- on September 27, 2021 by guest. Protected copyright. put forward. While quantitative studies have been ted from the site of infection in 106 of the 160 carried out in normal patients there is little in- patients and pathogens were isolated in 82 (77%), formation about changes in the faecal flora of the commonest being Bacterioides fragilis (21 patients with diarrhoea or colitis. patients), various species of streptococci (25 patients), In 1974 a prospective study of all patients in the and Staph. aureus (15 patients). The patients were High Wycombe group of hospitals receiving clinda- asked regularly by a research sister about the mycin or lincomycin was started and quantitative development of gastrointestinal side effects. Anti- bacterial counts were carried out on the faeces of biotic-induced diarrhoea was defined as the passage 160 patients. This paper describes the results and of watery faeces more than five times a day. Many compares the changes with the development of patients had mild changes in bowel function which gastrointestinal side effects. resolved within a few days of starting treatment. These were considered to be a result of surgery and Patients and methods not antibiotic therapy. Specimens of faeces collected from the patients Specimens of faeces were collected from 160 patients during the course of clindamycin or lincomycin -79 men and 81 women-including seven with therapy were delivered to the laboratory immediately and were examined within one hour. The faeces Received for publication 2 November 1977 were selectively cultured to determine the counts of 439 J Clin Pathol: first published as 10.1136/jcp.31.5.439 on 1 May 1978. Downloaded from 440 D. A. Leigh and K. Simmons four bacterial species-bacteroides, representing the of cases this was lower than 5 x 103 organisms per predominant anaerobic organisms, Enterobacteri- gram of faeces. In patients receiving lincomycin aciae, streptococci, and yeasts. streptococci were not increased in numbers as they A sample of faeces weighing about 1 g was were in patients receiving clindamycin. Otherwise disintegrated in 5 ml nutrient broth, serial hundred- both antibiotics produced similar changes, which fold dilutions (0-1 ml in 9-9 ml) were made in were independent of the route of administration of nutrient broth, and surface viable counts using the antibiotics. There was no difference between men 0-1 ml inocula were carried out on blood, and women in the faecal flora changes and the use MacConkey, and a special yeast agar incubated of combined antibiotic therapy did not influence aerobically and blood and neomycin blood agar the findings. (0-1 g/l) incubated anaerobically by the Gaspak Antibiotic-induced diarrhoea was seen in 25 (16%) method. The anaerobic agar was not prereduced. of patients and 87 (57%) patients had mild gastro- The plates were incubated for two days and the intestinal dysfunction related to surgery. The bacterial colonies counted. Bacteroides species were relationship of side effects to changes in flora are identified by their ability to grow on neomycin shown in Table 2. There were no differences be- blood agar and confirmed by either the API tech- tween the groups of patients apart from a higher nique (API Products Limited, Rayleigh, Essex) or incidence of increased yeast count when antibiotic- the Mastring (MID8) (Mast Laboratories Ltd., induced diarrhoea was present. Bootle, Merseyside). Strains of Enterobacteriaciae Although severe diarrhoea was nearly twice as and streptococci were identified by routine lab- common in patients who received prophylactic oratory techniques and yeasts by growth on the clindamycin or lincomycin (Table 3) this was not confirmed (Gram). special yeast agar by staining Table 2 Relation ofgastrointestinal side effects to It was impossible to examine pretreatment faecal changes in faecal flora in 153 patients (excluding specimens because most patients had been admitted patients with colostomies) as surgical emergencies which required immediate treatment. The accuracy of the faecal Normal Mild Antibiotic- antibiotic bowels changes induced collection and culture techniques was tested by diarrhoea examining specimens from a similar group of pre- No. of patients 41 87 25 operative surgical patients not receiving antibiotic Decreased anaerobic count 35 (85%) 86 (98 %) 24 (96%) therapy. Comparable bacterial counts to those Increased counts http://jcp.bmj.com/ were Enterobacteriaciae 21 (51 %) 52 (59%) 16 (64%) reported in normal volunteers found (Leigh Yeasts 11 (27%) 33 (38 %) 14 (56%) et al., 1976). Changes in the faecal bacterial counts Streptococci 6 (15%) 13 (15%) 7 (28%) were related to these normal findings and were considered significant when there was a decrease of Table 3 Incidence ofgastrointestinal side effects 106 or more organisms in the expected bacteroides related to the severity of the infection. Colostomy count, and an increase in the counts of Entero- patients excluded bacteriaciae (1(06 or more), streptococci (105 or more), Degree of infection Prophylaxis on September 27, 2021 by guest. Protected copyright. and yeast (103 or more). Smaller changes in the bacterial counts were not considered significant in Severe Moderate Minimal view of the techniques used. No side 48 65 4 11 effects or mild side Results effects Antibiotic- 10 (17%) 11 (15%) - 4 (27%) was a in the bacterioides induced There significant decrease diarrhoea count in all faecal specimens (Table 1) and in 95% Table 1 Changes in faecalflora in patients treated with clindamycin and lincomycin Clindamycin Lincomycin Total Parenteral Oral Parenteral Oral No. of patients 123 8 23 6 160 Decreased anaerobic count* 115 (93%) 8 23 6 152 (95%) Increased counts Enterobacteriaciae 74 (60%.) 6 (75%) 1 1 (48 %) 3 (50 %) 94 (59%) Yeasts 46 (37%) 2 (25%) 9 (39%) 3 (50%) 60 (38%) Streptococci 26 (21%) 2 (25%) - - 28 (18%) *Count < 5 x 103 bacteria per gram faeces. J Clin Pathol: first published as 10.1136/jcp.31.5.439 on 1 May 1978. Downloaded from Effect ofclindamycin and lincomycin therapy on faecalflora 441 reflected in changes in the faecal flora. Antibiotic- samples showed similar results and the normal induced diarrhoea was seen more often in women quantitative flora was restored after treatment was (19%) than men (13%) and this was most marked stopped (Leigh, unpublished). in those aged over 60 years of whom 30% of The incidence of diarrhoea (16%) with clinda- women were affected and only 11 % of men. mycin and lincomycin in our patients was similar to that found by Tedesco et al. (1974), but no cases of Discussion pseudomembranous colitis were seen in our 160 patients or in those in a longer follow-up study Gastrointestinal dysfunction after antibiotic treat- (Leigh et al., 1977). Possibly many of the reported ment has been related to many causal factors. cases of pseudomembranous colitis follow the irra- Certain antibiotics such as tetracycline and fusidic tional use of clindamycin and lincomycin for acid are toxic to the gastrointestinal tract either as a respiratory infections. The susceptibility of the direct effect, irrespective of concentration, or owing patient is different when a severe anaerobic infection to poor absorption allowing prolonged contact with is present. Strikingly, Bartlett et al. (1972), Fass the mucosa. The use of broad spectrum antibiotics et al. (1973), Gorbach and Thadephalli (1974), can result in the overgrowth of pathogenic bacteria and Chow et al. (1974) using clindamycin and lin- and yeasts such as Staphylococcus aureus, and Candida comycin in severe anaerobic infections have repor- albicans. In most of these cases quantitative bacteri- ted few cases of diarrhoea and no instances of pseudo- ology has not been investigated and it is not known membranous colitis.