Cleaning up Clostridium difficile infection

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paediatricians consider that uncomfortable, embarrassing, or painful anal manipulations such as rectal examination, enemas, or anorectal manometry should be avoided. The management advocated by van der Plas et al is rigorous— it includes rectal examination and anorectal studies at initial workup and daily enemas for 3–7 days thereafter. Why this difference in emphasis in management? Are there important cultural differences? Is it that British children are unduly modest about their bottoms, whereas Dutch children can tolerate such interventions with equanimity? Anal intervention can be avoided. Treatment without enemas can be successful for both initial clearout and long-term control.3,4 Van der Plas et al show that anorectal studies with a view to biofeedback training do not affect prognosis in the long term. Even rectal examination can be deferred and done only in cases not responding to medical treatment. Distress can be prevented by adequate early treatment of childhood constipation.1 Too many children receive inadequate doses of osmotic laxatives at presentation and insufficient follow-up. Worse still, inappropriate use of suppositories may bring on the anal pain that the child seeks to avoid. Enthusiastic management of constipation in the early stages without anal manipulation could perhaps reduce the numbers requiring more intensive workup in secondary or tertiary centres.

R C Beach Jenny Lind Children’s Department, Norfolk and Norwich Health Care NHS Trust, Norfolk NR1 3SR, UK 1 2 3

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Partin JC, Hamill SK, Fischel JE, Partin JS. Painful defecation and fecal soiling in children. Pediatrics 1992; 89: 1007–09. Claden G, Agnarsson U. Constipation in childhood. Oxford: Oxford Medical Publications, 1991. Gleghorn EE, Heyman MB, Rudolph CD. No-enema therapy for idiopathic constipation and encopresis. Clin Pediatr (Phila) 1991; 30: 669–72. Sprague-McRae JM, Lamb W, Homer D. Encopresis: a study of treatment alternatives and historical and behavioural characteristics. Nurse Pract 1993; 18: 52–53, 56–63.

Cleaning up Clostridium difficile infection Clostridium difficile infection affects mainly the elderly, among whom reported cases increased almost eight-fold between 1990 and 1994 in England and Wales. Here C difficile was the most commonly reported cause of intestinal infection in the elderly in 1994, ahead of both salmonella and campylobacter (figure).1 Elderly individuals may have impaired resistance to colonisation by C difficile,2 which in turn can lead to symptomless carriage, diarrhoea, or colitis (with or without pseudomembrane formation). C difficile is the commonest infective cause of hospital-acquired diarrhoea, but the true incidence of community-acquired C difficile infection is unknown because many laboratories do not routinely look for the bacterium or its toxin(s) in faecal specimens from general practice. Why is C difficile infection increasing? The obvious answer is that more antibiotics are being used. Antibiotics differ in their deleterious effects on the protective anaerobic gut flora. Cephalosporins in particular have received adverse publicity.3 However, since these have been widely used as workhorse antibiotics, denominator usage may distort the perceived risk of associated C difficile

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CDR Rev 1996; 6: R109

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infections. Unfortunately, too often workhorses are flogged unnecessarily; for example, the use of secondgeneration and third-generation cephalosporins in one US teaching hospital increased 7-fold and 6·5-fold, respectively, between 1978 and 1992.4 Doctors must be taught that non-essential antibiotic prescription (of any type) equals potentially avoidable morbidity and mortality from associated C difficile infection. Aminoglycosides, quinolones, ureidopenicillins, and trimethoprim seems less likely to promote C difficile infection.5,6 Policies recommending low-risk in preference to high-risk antibiotics can be targeted at units with a high incidence of C difficile infection, instead of struggling to achieve hospital-wide compliance. Blaming antibiotics alone is too simplistic. The frequently forgotten issue is the source of the bacterium. Infections usually result from C difficile strains acquired from other patients (particularly those with diarrhoea) or the environment, either directly or via the hands of healthcare personnel.7 Apart from specialist areas such as operating theatres, routine surveillance of microbial contamination of hospital environments is generally unhelpful, largely because it has not been possible to establish threshold levels associated with increased risk of infection. Whilst this tenet holds true, wards can become increasingly contaminated with C difficile spores, and intermittent surveillance can be useful to ascertain whether cleaning standards have been maintained. When the increasing number of cases of C difficile diarrhoea exceeds availability of single-occupancy rooms for the isolation of patients, spore contamination of open wards becomes a potential hazard. Spores can survive desiccation for months and are relatively resistant to conventional disinfectants. Thorough cleaning with detergents is relied upon to reduce the spore environmental burden, and inexpensive, user-friendly sporicides are needed.5 Mops and buckets are clearly not sacrosanct in these days of financial constraints on healthcare budgets, but we should resist pressure to reduce spending on cleaning. Where else can we point a finger? The prevalence of symptomless gut colonisation by C difficile in new admissions may be increasing, fuelled by a rise in the number of antibiotic prescriptions by general practitioners. In the UK this rise was greater than 60% 767

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COMMENTARY between 1980 and 1991.8 The occurrence of outbreaks of C difficile infection characterised by high mortality indicates that some strains are more virulent than others; we do not know whether there has been a shift in the pathogenicity of circulating bacteria. Having admission wards and intrahospital patient transfers in general are becoming more commonplace. Such practices are infection-control nightmares, increasing patient exposures to potential sources of C difficile and other bacteria, and possibly disseminating strains throughout several wards. C difficile is now endemic in many hospitals, and episodes of infection are expensive, each costing on average more than £4000, mainly because they increase hospital stay by a mean of 3 weeks.10 The war against C difficile infection clearly needs to be fought on several fronts. We can expect more elderly patients in the future, but we should not necessarily accept more antibiotic use. It is not surprising to find that the prevalence of C difficile on the hands of health-care personnel rises as the level of environmental contamination increases.10 Less time spent writing antibiotic prescriptions and more time hand washing would be a good starting point.

Mark H Wilcox Department of Microbiology, University of Leeds and General Infirmary, Leeds LS2 9JT, UK 1

Djuretic T, Ryan MJ, Fleming DM, Wall PG. Infectious intestinal disease in elderly people. Commun Dis Rep CDR Rev 1996; 6: R107–R12. 2 Borriello SP, Barclay FE. An in-vitro model of colonisation resistance to Clostridium difficile infection. J Med Microbiol 1986; 21: 299–309. 3 Impalallomeni M, Galletly NP, Wort SJ, et al. Increased risk of diarrhoea caused by Clostridium difficile in elderly patients receiving cefotaxime. Br Med J 1995; 311: 1345–46. 4 Pallares R, Dick R, Wenzel RP, Adams JR, Nettleman MD. Trends in antimicrobial utilization at a tertiary teaching hospital during a 15-year period (1978–1992). Infect Control Hosp Epidemiol 1993; 14: 376–82. 5 Anand A, Bashey B, Mir T, Glatt AE. Epidemiology, clinical manifestations, and outcome of Clostridium difficile diarhoea. Am J Gastroenterol 1994; 89: 519-23. 6 Department of Health and Public Health Laboratory Service Joint Working Group. Clostridium difficile infection. Prevention and management. London, 1994. 7 McFarland LV, Mulligan ME, Kwok RYY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320: 204–10. 8 Diseases fighting back. London: Parliamentary Office of Science and Technology, 1994. 9 Wilcox MH, Cunniffe JG, Trundle C, Redpath C. Financial burden of hospital-acquired Clostridium difficile infection. J Hosp Infect 1996; 34: 23–30. 10 Samore MH, Venkataraman L, DeGirolami PC, Arbeit RD, Karchmer AW. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996; 100: 32–40.

Mycobacteria and sarcoidosis Many clinicians, notably Scadding,1 have provided evidence of an association between mycobacterial infection and sarcoidosis, and it is relevant that Burnet2 discussed ways in which mycobacteria might be concerned in the causation of sarcoidosis; his principal suggestion was that they might be present in some form other than that of a culturable acid-fast bacillus, possibly in a protoplast or L form, lacking the power to produce the characteristic cell wall, and persisting as an intracellular parasite of mesenchymal cells. Almenoff et al,3 using a monoclonal antibody raised against Mycobacterium tuberculosis whole-cell antigen 768

(H37RV), have recently characterised acid-fast cell-walldeficient forms (CWDF) grown from the blood of patients with active sarcoidosis and have thereby confirmed that these organisms are mycobacterial in origin and similar, if not identical to, M tuberculosis. They anticipate that specific DNA sequencing will be required to determine whether these organisms are CWDF of M tuberculosis, a closely related atypical organism, or a unique species, and they emphasise that the contribution of any such organism to the pathogenesis of sarcoidosis is unknown. Their findings are in keeping with Burnet’s hypothesis and with those of Graham et al,4 who reported the culture of extremely fastidious cell-wall-defective acid-fast bacteria from skin lesions of patients with sarcoidosis. The findings of long-term controlled laboratory animal studies cited by Almenoff et al3 have been updated in successive reports; thus it has been reported that, although all human tissues studied had shown no acid-fast bacilli and had been negative on culture for mycobacteria, acidfast bacilli were seen in granulomatous tissue of mice passaged from the sarcoid tissues of six patients.5These organisms were found in the viscera 17 months or more after the injection of fresh homogenate or supernatant filtrate of mouse granulomatous tissue on first to third passage 3–9 years previously. Mycobacteria having the characteristics of human M tuberculosis were grown on Löwenstein-Jensen medium from pooled homogenates of lungs and spleens from mice in two of these serial passages. One of these originated in tissue from a patient with bilateral hilar lymphadenopathy who had a negative tuberculin test and a positive Kveim test; mouse lungs from the second passage and lungs and spleen from third and fourth passages grew M tuberculosis. It is highly relevant that two of these passages resulted from supernatant passed through a 0·2 µm filter. The other originated from a patient with bilateral hilar lymphadenopathy, pulmonary infiltration, and skin sarcoids and positive Kveim and negative tuberculin tests; from the second passage, which was with filtered supernatant, a homogenate of lungs and spleen grew M tuberculosis. Although Taub and Silzbach6 confirmed the initial finding of these animal experimental studies— namely, that granulomatous changes develop slowly after the injection of sarcoid homogenates into the footpads of mice—other investigators have been unable to repeat them and they continue to be viewed with scepticism. Nonetheless, the histological and bacteriological findings of these sequential animal experimental studies5 are in keeping with those of Almenoff et al3 and reflect the report of Moscovic7 in that the tubercle bacillus may exist interchangeably with a cell-wall-deficient form invisible to conventional staining techniques. As Almenoff et al cite, recent molecular studies have in general found a link between mycobacteria and sarcoidosis, but with widely variable results following the use of these highly sensitive molecular biological techniques (PCR) in relation to the detection of mycobacterial DNA in sarcoid tissues; current knowledge about sensitivity of this approach has been elegantly reviewed by Mangrapagan and Hance.8 As has been emphasised,3 the role of these mycobacterial CWDF forms in the pathogenesis of sarcoidosis is unknown. DNA sequencing will confirm whether, as seems probable from the results reported, they

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