Comment on ‘The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients’

Letters to the Editor eventual soil-transmitted helminths and for its mild toxicity. 3 On day 10 stool specimens were negative for larvae of S. stercoralis. The patient was discharged from the hospital on day 12. Faecal samples for microbiological follow-up remained negative over a period of 3 weeks. Our case describes the recovery of rhabditiform larvae in stool specimens of a subject without a recent clear exposure to a risk of infection. Interestingly, the only clear exposure to a risk of infection goes back to w h e n the w o m e n was 8 years old. At that time she lived in a rural district with low hygienic conditions and used to play bare-footed. In the absence of another clear exposure to a past or recent risk of infection (the patient was minutely questioned about the degree of exposure to risk factors, such as travel in emdemic areas, contamination of soil or water) one can speculate that the infection primarily occurred during her childhood. Previous case reports brought the attention to the long-term persistence of this nematode in former prisoners of World War II who had acquired the infection while held in captivity in endemic areas. 4'5 The mechanism of chronic infection by £ stercoralis is unknown, although autoinfection life cycle of S. stercoralis provides an intrinsic :means for extended incubation periods in humans and imnmnodepression is classically evoked to explain the proliferation of the parasite.~ Recently in a mouse model study a dichotomy of the protective i m m u n e response to infective and autoinfective larvae has been shown. The presence of a difference in antigen recognition between infective and autoinfective larvae could explain why the latter are able to evade the i m m u n e response in chronically infected hosts. 6 Other hypotheses has been evaluated to identify the mechanism of chronic strongyloidiasis to explain delayed onset recrudescence in humans. One of these provided that the chronic infections result from periodic reactivation of infective larvae from a reservoir of dormant parasites outside the gastrointestinal tract.7 A more likely hypothesis suggested a periodic rejuvenation of post-reproductive longlived female worms lodged in the mucosal crypts, which under specific circumstances (e.g. immunosuppression, corticosteroid therapy) were once again capable of producing viable larvae. 7 Our u n c o m m o n case leads to a question about the possibility of an u n l m o w n transmission or a late recrudescence of the infection, even if the possibility of a late recrudescence of the infection should be more likely. This hypothesis is corroborated by the presence of the poor physical conditions and by the possibility of impairment of the i m m u n e status due to the chronic renal failure and to the elderly. Actually, the fact that circumstances related to suppression of the host's i m m u n e response (particularly T cell function) lead to an overwhelming parasite load is well known. ~'s-30 Finally, our case seems to be particularly interesting for the extremely late recrudescence of the infection that relapsed after 70 years.

A. Giacometti, O. Cirioni, D. Drenaggi, E Compagnucci, M. Quarta, M. Fortuna and G. Scalise Institute of Infectious Diseases f~ Public Health, Univel~sity of Ancona, Italy

References 2 Mahmoud AAF. Strongyloidiasis. l Clin Infect Dis 1996; 23: 949953. 2 Genta RM. Global prevalence of strongyloides: critical review with epidemiologic insight into the prevention of disseminated disease. Rev Infect Dis 1989; 11: 755-765.

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3 Marti H, Haji H, Savioli L. et al. A comparative trial of a singledose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil-transmitted hehninth infections in children. Am ] Trop Med Hyg 1996; 55: 477-481. 4 Gill GV, Bell DR. Strongyloides stercoralis infection in former Far East prisoners of war. BMJ 1979; 2: 572-574. 5 Grove DI. Strongyloidiasis in allied ex-prisoners of war in SouthEast Asia. BM] 1980; 280: 598-601. 6 Brigandi RA, Rotman HE, Nolan TJ, Schad GA, Abraham D. Chronicity in Strongyloides infections: dichotomy of the protective immune response to infective and autoinfective larvae in a mouse model. Am I Trop Med Hyg 1997; 56: 640-646. 7 Mansfield LS, Niamatali S, Bhopale Vet aI. Strongyloides stercoralis: maintenance of exceedingly chronic infections. Am ] Trop Med Hyg 1996; 55: 617-624. 8 Gompels MM, Todd l, Peters PS, Main J, Pinching AJ. Disseminated strongyloidiasis in AIDS: uncommon but important. AIDS 1991; 5: 329-332. 9 Lessnau KA), Can S, Talavera W. Disseminated Strongyloides stercombs in human immunodeflciency virus-infected patients. Chest 1993; 104: 119-122. 10 Schainberg L, Scheinberg MA. Recovery of Strongyloides stercoralis by bronchoalveolar lavage in a patient with acquired immunodeficiency syndrome. Am ] Med 1989; 87: 486.

Accepted for publication 9 Jul9 1998

Comment on "The Lack of Therapeutic Effect of Saccharomyces boulardii in the Prevention of Antibiotic-related Diarrhoea in Elderly Patients' Sir, S. J. Lewis et al. reported in an earlier volume of The Journal of Infection (1998; 36: 1 7 1 - 1 7 4 ) that Saccharomyces boulardii was ineffective in preventing antibiotic-related diarrhoea (AAD) in elderly patients. 1 This small trial failed to prove this conclusion due to a problem in the study design. Patients were evaluated only while on antibiotics, with no follow-up after antibiotics were discontinued. Unfortunately, the average time patients were on the study was only 6-11 days, which is an insufficient time of follow-up for AAD. Published studies of antibiotic-related diarrhoea find that the onset of AAD usually occurs after antibiotics have been discontinued, and the recommended time of follow-up is 6-8 weeks after antibiotics. Anand et al. followed 60 patients for 6 weeks after antibiotics to determine the frequency of Clostridium difficile-related AAD. 2 Bulstrode et al. followed 180 patients who received intravenous cefuroxime as prophylaxis for aortic surgery and reported that the onset of AAD ranged from 3 to 16 days, with a median of 6 days after antibiotics. 3 James et al. reported that the onset of diarrhoea ranged from 2 - 3 0 days after antibiotics had been given. 4 Morris et al. reported that while patients commonly present within 1 week after receiving antibiotics, up to 40% will develop symptoms 2 - 1 0 weeks after antibiotics, s The authors have misquoted a previous study by us (Am J Gastroenterol) 1995; 90: 4 3 9 - 4 4 8 ) as inability 'to show benefit in another ... study (5.2% vs. 8.3%, P value not given)'. 6 These percentages reflect the frequency of diarrhoea only while patients were on the antibiotics. The study was designed to have the appropriate follow-up period (7 weeks post-antibiotics)

Letters to the Editor

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so that the diarrhoea that developed after antibiotics would be observed and analysed. Over one-third (38%) of the cases of AAD did develop during this post-antibiotic period (21-28 clays after antibiotics). W h e n the apppropriate follow-up period was analysed, S. boulardii was found to significantly prevent antibiotic-associated diarrhoea (7.2%) compared to placebo (14.6%, P = 0 . 0 2 ) . 6 For the study of AAD it is imperative that patients be followed for at least 1 m o n t h post-antibiotics. Failure to do so, as in the study by Lewis et al., precludes making a valid conclusion on the efficacy of any intervention, such as S. boulardii.

We were not trying to misquote the above authors' paper. ~ We deliberately chose to present their data for patients on antibiotic treatment as it is directly comparable with our own. We also presented their overall data. This distinction between the two sets of data is made quite clear in the discussion, as is the reason for choosing the dose used of S. boulardii which has been shown to be efficious in a previous study. 3 None of the patients who experience diarrhoea were taking laxatives. As to the effectiveness of probiotic therapy, whilst I realize there are some converts, we have also written a review ~ and do not share their enthusiasm!

G. W. ElmeP, and L. V. McFarland 1'2 ~Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 9 8 1 9 5 U.S.A. and 2Biocode~, Inc. 1910 Fairview Avenue East, Suite 208, Seattle, WA 98102, U:S.A.

S. Lewis and L. Potts

University of Wales, Heath Park, Cardiff CF4 4XW, U.K

References

References 1 Lewis SJ, Potts LF, Barry RE. The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients. J Infect 1998; 36: 171-174. 2 Anand A, Bashey B, Tanveer M, Glatt AE. Epidemiology, clinical manifestations, and outcome of Clostridiurn difficile-associated diarrhoea. Am ] Gastroenterol 1994; 89: 519-523. 3 Bulstrode NW, Branbury AW, Barrett Set al. Clostridium ddfficilecolitis after aortic surgery. Eur J Vase Endocase 1997; 14: 217-220. 4 James AH, Katz VL, Dotters DJ, Rogers RG. Clostridium difficile infection in obstetric and gynecologic patients. South Med J 1997; 90: 889-892. 5 Morris JB, Zollinger RM, Stellato TA. Role of surgery in antibioticinduced pseudomembranous enterocolitis. Am J Surg 1990; 160: 535-539. 6 McFarland LV, Surawicz CM, Greenberg RN et al. Prevention of [3lactam-associated diarrhoea by Saeeharomyces boulardii compared with placebo. Am J Gastroenterol 1995; 90: 439-448.

1 McFarland LV, Surawicz CM, Greenburg RN et al. Prevention of 13lactam associated diarrhoea by Saccharomyees boulardii compared with placebo. Am ] Gastroenterol 1995; 90: 439-448. 2 James AH, Katz VL, Dotters DJ, Rogers RG. Clostridium diJyieile infection in obstetric and gynecologic patients. South IVied J 1997; 90: 889-892. 3 Adam J, Barret A, Barret-Bellet C. Essais cliniques contr616s en double insu de l'ultra-leure lyophilis6e, l~tude multicentrique par 25 m4decins de 388 cas. Gag M~d Francaise 1977; 84: 20722078. 4 Lewis SJ, Freedman AR. The use of biotherapeutic agents in the prevention and treatment of gastrointestinal disease. Aliment Pharmacol Ther 1998; in press.

Toxic shock-like syndrome caused by group G

Streptococcus

Accepted for publication 14 July 1998 Sir,

Authors" reply Sir, In response to the comments by Elmer and McFarland. Their association with Biocodex the company who manufactures Saccharomyces boulardii should be noted. Our study was concerned with the prevention of antibiotic-related diarrhoea in elderly patients on General Medical wards. Whilst antibioticrelated diarrhoea can occur after cessation of antibiotic therapy, it is debatable whether the majority occurs at this stage. This is certainly not the case for diarrhoea due to Clostridium difficile. The above authors' own publications do not support the majority of antibiotic related diarrhoea occurring after cessation of antibiotic treatment. 1 We have followed up 60 medical patients over the age of 65 for 2 weeks after stopping antibiotics. Fourteen (23%) patients developed diarrhoea. Only one patient developed diarrhoea after stopping antibiotics. The publication quoted by the above authors 2 is a retrospective study of hospital records looking at a quite different group of patients (obstetric and gynaecological). We do agree, however, that it would have been preferable to have followed up our patients after discharge from hospital.

We herein report a case of TSLS caused by group G Streptococcus, which took a rapidly fatal course in spite of performing aggressive treatment. A 59-year-old Japanese m a n with a 3-day history of giant blisters, including a 1-day history of a painful erythematous ulcer with necrosis on his right lower extremity, was admitted to our institution complaining of dyspnoea and swollen legs. The physical findings included blood pressure 110/60 mmHg; heart rate 100/min; a respiration rate 20/min; axillary temperature 3 7.5 °C. The entire right lower extremity was markedly swollen with erythema, purpura and a 10 cm diameter ulcer with necrosis. Two blisters on the back of his right foot were seen at the time of the admission to our institution. Laboratory studies showed: white blood cell count, 11 700/gl; haematocrit, 59.3%; platelets, l 1 4 0 0 0 / p l ; C-reactive protein, 14.9 mg/dl and antistreptolysin O level, 62 1V/ml (reference value < 2 0 0 IU/ ml). An arterial blood gas analysis, room air condition, showed pit 7.336; PaCO2, 65.1 tort; PaO2, 37.9 torr and SaO2, 68.1%. A serological analysis, HIV antibody, HBS antigen, HCV antibody, RPR, TPHA were all negative, Several hours after admission, the patient developed disturbed consciousness, severe dyspnoea and hypotension, blood pressure 5 0 / 4 0 mmHg. Debridement was performed on the necrotic