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Clostridium difficile in the elderly
Letters to the E d i t o r
3IO
between H P V / B I 9 infection and rheumatoid arthritis which we and others have previously observed epidemiologically. 7-9
Miyagi Prefectural Institute of Public Health, 4-7-2, Saiwaicho, Sendai 983 The Second Department of Internal Medicine Department of Microbiology, Tohoku University School of Medicine, 2 - I , Seiryo-machi, Sendai 980, Japan
Hiroyuki Shiraishi Takeshi Sasaki Masataka Nakamura Nobuo Yaegashi Kazuo Sugamura
References I. White DG, Woolf AD, Mortimer PP et al. Human parvovirus arthropathy. Lancet I985;
i: 419-42I. 2. Plummer FP, Hammond GW, Forward K et al. An erythema infectiosum-like illness caused by human parvovirus infection. N Engl J Med I985; 3x3 : 74-79. 3. Bell LM, Naides SJ, Stoffman P e t al. An erythema infectiosum-like illness caused by human parvovirus infection. N EnglJ Med z989; 32x: 485-49I. 4. Shiraishi H, Umetsu K, Yamamoto H et al. Human parvovirus (HPV/BIg) infection with purpura. Microbiol Immunol I989; 33: 369-372. 5. Nunoue T, Koike T, Koike R et al. Infection with human parvovirus (BI9), aplasia of the bone marrow and a rash in hereditary spherocytosis. J Infect I987; x4: 67-70. 6. Anderson MJ, Higgins PG, Davis LR et al. Experimental parvovirus infection in humans. J Infect Dis I985; x52: 257-265. 7. Sasaki T, Takahashi Y, Yoshinaga K et al. An association between human parvovirus B-r 9 infection and autoantibody production. J Rheumat z989; x6: 708. 8. Reid DM, Reid TMS, Brown T et al. Human parvovirus-associated arthritis: a clinical and laboratory description. Lancet I985; i: 422-425 . 9. Cohen BJ, Buckley MM, Clewley JP et al. Human parvovirus infection in early rheumatoid and inflammatory arthritis. Ann Rheum Dis x986; 45: 832-838. zo. Clewley JP. Detection of human parvovirus using a molecularly cloned probe, ff Med Virol I985; I5: I73-I8I. II. Yaegashi N, Shiraishi H, Takeshita T et al. Propagation of human parvovirus BI9 in primary culture of erythroid lineage cells derived from fetal liver, ff Virol I989; 63: 2422-2426.
C l o s t r i d i u m d i ~ c i l e i n the elderly Accepted for publication IO December 199o Sir, Corrado et al., 1 report in the N o v e m b e r I99o issue of this journal a low carriage rate (4 %) of Clostridium difficile in elderly patients on a mixed-function geriatric ward. As their findings support the low carriage rate reported by Campbell et al.fl and contradict the higher rates reported by othersf1-5 they r e c o m m e n d further comparative studies of various institutional settings so as to ensure that earlier reports of high carriage rates do not merely reflect outbreaks of infection. W e conducted a short similar study on C. difficile carriage in elderly patients in hospital that m a y therefore be of interest. Nineteen specimens were collected over a period of 13 weeks from I7 patients (mean age 78 years, range 68-97 years) consisting of nine m e n and eight women. N o n e of t h e m had diarrhoea at the time of sampling or had received antibiotics in the preceding 4 weeks. All faecal specimens were tested both directly ~ and following enrichment in a selective broth for C. difficile and for cytotoxicity to V E R O cells/
Letters to the E d i t o r
311
Samples from one 83-year-old w o m a n and one 82-year-old m a n showed evidence of C. difficile. T h e first patient harboured a cytotoxigenic strain on two separate occasions (i2 days apart) but on neither occasion was cytotoxin detected in the faeces. T h e second patient h a r b o u r e d a non-toxigenic strain on the one occasion he was sampled. For both patients, enrichment of samples was unnecessary in order to detect C. difficile. Varki and Aquino found that samples from 8/72 (I 1 % ) patients in hospital who had not received antibiotics within the preceding 3 months yielded C. difficile, although in their study m a n y of the patients had diarrhoea and the presence of C. difficile was not restricted to the elderly. O u r isolation rate of 11.8 % is higher than that reported by Corrado et al., 1 which is surprising in that most of their patients were receiving or had recently received antibiotics, their two positive patients falling into this group. N o n e of their I5 antibiotic-free patients was positive. O u r figure, however, is in keeping with the I6 % culture or toxin-positive faecal samples from I9 long-stay geriatric patients who, like our patients, had not received antibiotics within 4 weeks and did not have diarrhoea. 4 It is still not clear whether C. difficile is naturally a m o r e frequent c o m p o n e n t of the faecal flora in the elderly. Usually, comparisons are made with the approximate 4 % incidence in the normal population without c o m m e n t i n g on the fact that it is difficult to determine accurately the frequency in any given age group. Moreover, the figure most often given refers to unpublished observations quoted by George et al., s' 9 and based on work that preceded development of an effective selective medium. Equally, the effect of being in hospital and the associated increased risk of exposure to C. difficile should be statistically controlled by comparison with a similar but younger patient age group. T h e r e is some indirect evidence, however, that the elderly m a y be naturally m o r e susceptible to colonisation with C. difficile. It was shown in an in vitro model that the faecal flora of aged adults is less efficient at exerting an inhibitory effect on the growth of C. difficile3 ° T h e r e is also evidence that changes in the gut flora predispose to colonisation with other clostridial species such as C. perfringens ~ and C. paraputrificum (Borriello, unpublished). T h e overall indications are that the elderly may be m o r e predisposed to colonisation by C. difficile and that this predisposition m a y be reflected by an increased rate of isolation of the organism. Since this hypothesis remains to be proven, however, Corrado et al. ~ quite rightly question it.
Microbial Pathogenicity Research Group, Clinical Research Centre, Warlord Road, Harrow, Middlesex H A I 3 UJ, U.K.
I. 2. 3. 45. 6. 7.
S. P. Borriello F. E. Barclay
References Corrado OJ, Mascie-Taylor BH, Hall MJ, Bolton RP. Prevalence of Clostridium di.~icile on a mixed-function ward for the elderly. J Infect I99o; 2x: 287-292. Campbell RR, Beere D, Wilcock GK, Brown EM. Clostridium di~cile in acute and long stay elderly patients. Age Ageing I988; x7: 333-336Bender BS, Laughon BE, Gaydos C et al. Is Clostridium digO~cileendemic in chronic-care facilities? Lancet i986; ii: I I - I 3. Woodhouse KW, Elliot TSJ, Stansfield E. Hospital outbreaks of Clostridium difficile. Lancet I986; ii: 75I. Nakamura S, Mikawa M, Nakshio S, Takabatake M, Okado I, Yamakawa K, Serikawa T, Okumura S, Nishida S. Isolation of Clostridium difficile from the feces and the antibody in sera of young and elderly adults. Microbiol Immunol x98x ; 25: 345-35I. Borriello SP, Honour P, Turner T, Barclay F. Household pets as a potential reservoir for Clostridium difficile infection. J Clin Pathol I983; 36: 84-87. Kamiya S, Reed PJ, Borriello SP. Analysis of purity of Clostridium difficile toxin A derived
3 I2
8.
9IO. I I,
Letters to the Editor by affinity chromatography on immobilized bovine thyroglobulin. F E M S Microbiol Lett 1988; 86: 331-336. George WL, Sutter VL, Finegold SM. Toxigenicity and antimicrobial susceptibility of Clostridium difficile a cause of antimicrobial agent-associated colitis. Current Microbiol 1978; I : 55-58. George WL, Rolfe RD, Sutter VL, Finegold SM. Diarrhea and colitis associated with antimicrobial therapy in man and animals. Am J Clin Nutr 1979; 32: 251-257. Borriello SP, Barclay FE. An in vitro model of colonisation resistance to Clostridium difficile infection. J Med Microbiol 1986; 2I : 299-309. Yamagishi T, Serikawa T , Morita R. Persistent high number of Clostridium perfringens in the intestines of Japanese adults. Jap J Microbiol 1976; 2o: 397-403.
3IO
between H P V / B I 9 infection and rheumatoid arthritis which we and others have previously observed epidemiologically. 7-9
Miyagi Prefectural Institute of Public Health, 4-7-2, Saiwaicho, Sendai 983 The Second Department of Internal Medicine Department of Microbiology, Tohoku University School of Medicine, 2 - I , Seiryo-machi, Sendai 980, Japan
Hiroyuki Shiraishi Takeshi Sasaki Masataka Nakamura Nobuo Yaegashi Kazuo Sugamura
References I. White DG, Woolf AD, Mortimer PP et al. Human parvovirus arthropathy. Lancet I985;
i: 419-42I. 2. Plummer FP, Hammond GW, Forward K et al. An erythema infectiosum-like illness caused by human parvovirus infection. N Engl J Med I985; 3x3 : 74-79. 3. Bell LM, Naides SJ, Stoffman P e t al. An erythema infectiosum-like illness caused by human parvovirus infection. N EnglJ Med z989; 32x: 485-49I. 4. Shiraishi H, Umetsu K, Yamamoto H et al. Human parvovirus (HPV/BIg) infection with purpura. Microbiol Immunol I989; 33: 369-372. 5. Nunoue T, Koike T, Koike R et al. Infection with human parvovirus (BI9), aplasia of the bone marrow and a rash in hereditary spherocytosis. J Infect I987; x4: 67-70. 6. Anderson MJ, Higgins PG, Davis LR et al. Experimental parvovirus infection in humans. J Infect Dis I985; x52: 257-265. 7. Sasaki T, Takahashi Y, Yoshinaga K et al. An association between human parvovirus B-r 9 infection and autoantibody production. J Rheumat z989; x6: 708. 8. Reid DM, Reid TMS, Brown T et al. Human parvovirus-associated arthritis: a clinical and laboratory description. Lancet I985; i: 422-425 . 9. Cohen BJ, Buckley MM, Clewley JP et al. Human parvovirus infection in early rheumatoid and inflammatory arthritis. Ann Rheum Dis x986; 45: 832-838. zo. Clewley JP. Detection of human parvovirus using a molecularly cloned probe, ff Med Virol I985; I5: I73-I8I. II. Yaegashi N, Shiraishi H, Takeshita T et al. Propagation of human parvovirus BI9 in primary culture of erythroid lineage cells derived from fetal liver, ff Virol I989; 63: 2422-2426.
C l o s t r i d i u m d i ~ c i l e i n the elderly Accepted for publication IO December 199o Sir, Corrado et al., 1 report in the N o v e m b e r I99o issue of this journal a low carriage rate (4 %) of Clostridium difficile in elderly patients on a mixed-function geriatric ward. As their findings support the low carriage rate reported by Campbell et al.fl and contradict the higher rates reported by othersf1-5 they r e c o m m e n d further comparative studies of various institutional settings so as to ensure that earlier reports of high carriage rates do not merely reflect outbreaks of infection. W e conducted a short similar study on C. difficile carriage in elderly patients in hospital that m a y therefore be of interest. Nineteen specimens were collected over a period of 13 weeks from I7 patients (mean age 78 years, range 68-97 years) consisting of nine m e n and eight women. N o n e of t h e m had diarrhoea at the time of sampling or had received antibiotics in the preceding 4 weeks. All faecal specimens were tested both directly ~ and following enrichment in a selective broth for C. difficile and for cytotoxicity to V E R O cells/
Letters to the E d i t o r
311
Samples from one 83-year-old w o m a n and one 82-year-old m a n showed evidence of C. difficile. T h e first patient harboured a cytotoxigenic strain on two separate occasions (i2 days apart) but on neither occasion was cytotoxin detected in the faeces. T h e second patient h a r b o u r e d a non-toxigenic strain on the one occasion he was sampled. For both patients, enrichment of samples was unnecessary in order to detect C. difficile. Varki and Aquino found that samples from 8/72 (I 1 % ) patients in hospital who had not received antibiotics within the preceding 3 months yielded C. difficile, although in their study m a n y of the patients had diarrhoea and the presence of C. difficile was not restricted to the elderly. O u r isolation rate of 11.8 % is higher than that reported by Corrado et al., 1 which is surprising in that most of their patients were receiving or had recently received antibiotics, their two positive patients falling into this group. N o n e of their I5 antibiotic-free patients was positive. O u r figure, however, is in keeping with the I6 % culture or toxin-positive faecal samples from I9 long-stay geriatric patients who, like our patients, had not received antibiotics within 4 weeks and did not have diarrhoea. 4 It is still not clear whether C. difficile is naturally a m o r e frequent c o m p o n e n t of the faecal flora in the elderly. Usually, comparisons are made with the approximate 4 % incidence in the normal population without c o m m e n t i n g on the fact that it is difficult to determine accurately the frequency in any given age group. Moreover, the figure most often given refers to unpublished observations quoted by George et al., s' 9 and based on work that preceded development of an effective selective medium. Equally, the effect of being in hospital and the associated increased risk of exposure to C. difficile should be statistically controlled by comparison with a similar but younger patient age group. T h e r e is some indirect evidence, however, that the elderly m a y be naturally m o r e susceptible to colonisation with C. difficile. It was shown in an in vitro model that the faecal flora of aged adults is less efficient at exerting an inhibitory effect on the growth of C. difficile3 ° T h e r e is also evidence that changes in the gut flora predispose to colonisation with other clostridial species such as C. perfringens ~ and C. paraputrificum (Borriello, unpublished). T h e overall indications are that the elderly may be m o r e predisposed to colonisation by C. difficile and that this predisposition m a y be reflected by an increased rate of isolation of the organism. Since this hypothesis remains to be proven, however, Corrado et al. ~ quite rightly question it.
Microbial Pathogenicity Research Group, Clinical Research Centre, Warlord Road, Harrow, Middlesex H A I 3 UJ, U.K.
I. 2. 3. 45. 6. 7.
S. P. Borriello F. E. Barclay
References Corrado OJ, Mascie-Taylor BH, Hall MJ, Bolton RP. Prevalence of Clostridium di.~icile on a mixed-function ward for the elderly. J Infect I99o; 2x: 287-292. Campbell RR, Beere D, Wilcock GK, Brown EM. Clostridium di~cile in acute and long stay elderly patients. Age Ageing I988; x7: 333-336Bender BS, Laughon BE, Gaydos C et al. Is Clostridium digO~cileendemic in chronic-care facilities? Lancet i986; ii: I I - I 3. Woodhouse KW, Elliot TSJ, Stansfield E. Hospital outbreaks of Clostridium difficile. Lancet I986; ii: 75I. Nakamura S, Mikawa M, Nakshio S, Takabatake M, Okado I, Yamakawa K, Serikawa T, Okumura S, Nishida S. Isolation of Clostridium difficile from the feces and the antibody in sera of young and elderly adults. Microbiol Immunol x98x ; 25: 345-35I. Borriello SP, Honour P, Turner T, Barclay F. Household pets as a potential reservoir for Clostridium difficile infection. J Clin Pathol I983; 36: 84-87. Kamiya S, Reed PJ, Borriello SP. Analysis of purity of Clostridium difficile toxin A derived
3 I2
8.
9IO. I I,
Letters to the Editor by affinity chromatography on immobilized bovine thyroglobulin. F E M S Microbiol Lett 1988; 86: 331-336. George WL, Sutter VL, Finegold SM. Toxigenicity and antimicrobial susceptibility of Clostridium difficile a cause of antimicrobial agent-associated colitis. Current Microbiol 1978; I : 55-58. George WL, Rolfe RD, Sutter VL, Finegold SM. Diarrhea and colitis associated with antimicrobial therapy in man and animals. Am J Clin Nutr 1979; 32: 251-257. Borriello SP, Barclay FE. An in vitro model of colonisation resistance to Clostridium difficile infection. J Med Microbiol 1986; 2I : 299-309. Yamagishi T, Serikawa T , Morita R. Persistent high number of Clostridium perfringens in the intestines of Japanese adults. Jap J Microbiol 1976; 2o: 397-403.