1467
TABLE l-LATEX AGGLUTINATION AND CULTURE RESULTS
customers’ requirements. Since 96 % of people we surveyed wished to be called patients this view should be respected by all health-care providers. We would encourage those who want to care for patients in both the private and public sectors to treat them as such. Leicester General Hospital, Leicester LE5 4PW. UK
C. S. J. PROBERT T. BATTCOCK J. F. MAYBERRY
Horse chestnut seed extract SIR,—Professor Schonhofer (March 31,
p 788) describes Klinge company that sues authors who publish negative on horse chestnut seed extract (’Venostasin retard’), suggesting that the company uses litigation to restrict the freedom of science. This is not true. The author of the book in question stated that the efficacy of treatment with venostasin could not be replicated and that the risk-benefit ratio was unacceptable because of adverse drug reactions that have not been reported to the West German drug-regulatory authority or to the manufacturers. The author was not willing to withdraw this libel and recourse to the law was the only way for Klinge Pharma to protect itself against such unfounded
Pharma verdicts
as a
statements.
reduction in transcapillary filtration rate is a effect of venostasin retard, proved in a randomised, placebo-controlled crossover trial in volunteers and in patients.1 The reduction in and prevention of peripheral venous oedema are clinically relevant and reflect the therapeutic efficacy demonstrated in randomised, controlled trials.2-4 These trials have been reviewed by Hitzenberger. The independent scientific expert appointed by the court attested to the clinical efficacy of venostasin retard. Klinge Pharma regrets the need for litigation, but there was no other way. A
22%
pharmacological
Medical Department, Klinge Pharma Gmbh,
D-8000 Munich 80, West Germany
*5 patients not tested adequately upon admission tPattents were observed for diarrhoea during hospital stay. ‡Administration of antimicrobial agents during 2 months
preceding admission
collected upon admission. 218 patients were tested on admission and a further 5 were followed up. Further samples were taken after 2 and 4 weeks and extra samples were taken during any period of diarrhoea during the hospital stay. Stools were cultured, 2-18 h after collection, on selective medium. Colonies with characteristic morphology and staining gram-positive were confirmed as C difficile by membrane gas-chromatography.5 We used the ’Culturette’ rapid latex test (Marion Scientific) and followed the manufacturer’s guidelines carefully, the controls required being included. 84 C difficile latex agglutination positive samples, 29 culture positive samples (23 also positive on the latex test), and 17 negative samples in both tests were further studied by tissue cytotoxin assay.6 A cytopathic effect was confirmed by C sordellii antitoxin neutralisation. Samples, frozen at 40°C, were thawed and filtered just before assay, a procedure that does not result in loss of reactivity. 126 patients were admitted to the outbreak ward and 92 to the control ward. Upon admission 29% were positive by latex agglutination and 11 % by culture (table I). Diarrhoeal episodes were noted in 21 patients-14 were in the outbreak ward and 7 in the control ward; 11 were latex positive and 10 were culture positive (table i). Stool cultures of the diarrhoea patients revealed growth of no other intestinal bacterial or viral pathogen. 10 % of the 197 patients without diarrhoea were C difficile culture positive and 39% were latex agglutination positive. Both tests were positive in 5%. Of the 84 latex positive samples selected for further study 6 were positive in the cytotoxin assay (table II). The corresponding figure for culture-positive stools was 21%. The sensitivities of the latex test and culture were 100% but for specificity was only 23% and 77%, respectively, for an overall accuracy of 27% and 79%. Of the 218 patients 27% had had infections treated with an antimicrobial agent before admission or during the hospital stay. C difficile culture was positive or turned positive in 57% of the 59 antibiotic users but in only 8% of the 159 patients without antibiotic use. In the latex agglutination test the figures for antibiotic users and non-users were 54% and 35%, respectively. The finding of many false-positive C difficile latex tests among stool samples collected on geriatric wards has prompted us to reconsider our policy on antimicrobial treatment for C difficilerelated diseases. We used to give vancomycin or metronidazole to patients with diarrhoea who were latex agglutination positive, and patients were often isolated. We now use culture as a first-line test, because it is more specific than the latex test. Latex agglutination
first stool
sample was
admitted; 213
were
-
MICHAEL BECK
1. Bisler
H, Pfeiffer R, Klüken N, Pauschinger P. Wirkung von Roßkastaniensamenextrakt auf die transkapillare Filtration bei chronischer venoser Insuffizien. Dtsch Med Wochenschr 1986; 35: 1321. 2. Rudofsky G, Neiß A, Otto K, Seibel K. Ödemprotektive Wirkung und klinische Wirksamkeit von Roßkastaniensamenextrakt im Doppelblindversuch. Phlebol Proktol 1986; 15: 47. 3. Sterner M, Hillemanns HG. Untersuchung zur odemprotektiven Wirkung eines Venentherapeutikums. Munch Med Wochenschr 1986; 31: 551. 4 Marshall M, Dormandy JA. Oedema of long distant flights. Phlebology 1987; 2: 123. 5. Hitzenberger G. Die therapeutische Wirksamkeit des Roßkastaniensamenextraktes. Wien Med Wochenschr 1989; 17: 385.
False-positive Clostridium difficile latex agglutination tests SIR,-Clostridium difficile is responsible for pseudomembranous colitis and antibiotic-associated diarrhoea. C difficile-associated diseases are diagnosed by stool culture, by tissue culture for cytotoxin, and by a rapid latex agglutination test. All three tests have disadvantages. Culture detects all strains of C difficile, irrespective of toxin-producing capacity; the cytotoxin assay is widely accepted but is not standardised; and the latex test detects factors related to C difficile-associated diseases but not toxin A itself. 1,2 A combination of tests has been recommended3,.. but immediate decisions are usually made on the latex agglutination result. In April and May, 1988, there was an outbreak of diarrhoea on a geriatric ward in Turku City Hospital. We investigated all patients in the affected ward and in a control ward using routine culture techniques for all clinically important intestinal pathogens, including C difficile culture and latex-agglutination test. The wards did not differ with respect to the frequency of latex agglutinationpositive faecal samples (37% outbreak ward, 40% control ward) but C difficile cultures were positive at rates of 18% and 3%, respectively (p < 0-02). Most inpatients at the department of medicine, Turku City Hospital, are geriatric and long-stay. All patients admitted to the outbreak ward and a control ward from June to December, 1988, were investigated by C difficile culture and latex agglutination. The
or
during hospital stay
TABLE ll-CYTOTOXIN, LATEX, AND CULTURE RESULTS
TABLE l-LATEX AGGLUTINATION AND CULTURE RESULTS
customers’ requirements. Since 96 % of people we surveyed wished to be called patients this view should be respected by all health-care providers. We would encourage those who want to care for patients in both the private and public sectors to treat them as such. Leicester General Hospital, Leicester LE5 4PW. UK
C. S. J. PROBERT T. BATTCOCK J. F. MAYBERRY
Horse chestnut seed extract SIR,—Professor Schonhofer (March 31,
p 788) describes Klinge company that sues authors who publish negative on horse chestnut seed extract (’Venostasin retard’), suggesting that the company uses litigation to restrict the freedom of science. This is not true. The author of the book in question stated that the efficacy of treatment with venostasin could not be replicated and that the risk-benefit ratio was unacceptable because of adverse drug reactions that have not been reported to the West German drug-regulatory authority or to the manufacturers. The author was not willing to withdraw this libel and recourse to the law was the only way for Klinge Pharma to protect itself against such unfounded
Pharma verdicts
as a
statements.
reduction in transcapillary filtration rate is a effect of venostasin retard, proved in a randomised, placebo-controlled crossover trial in volunteers and in patients.1 The reduction in and prevention of peripheral venous oedema are clinically relevant and reflect the therapeutic efficacy demonstrated in randomised, controlled trials.2-4 These trials have been reviewed by Hitzenberger. The independent scientific expert appointed by the court attested to the clinical efficacy of venostasin retard. Klinge Pharma regrets the need for litigation, but there was no other way. A
22%
pharmacological
Medical Department, Klinge Pharma Gmbh,
D-8000 Munich 80, West Germany
*5 patients not tested adequately upon admission tPattents were observed for diarrhoea during hospital stay. ‡Administration of antimicrobial agents during 2 months
preceding admission
collected upon admission. 218 patients were tested on admission and a further 5 were followed up. Further samples were taken after 2 and 4 weeks and extra samples were taken during any period of diarrhoea during the hospital stay. Stools were cultured, 2-18 h after collection, on selective medium. Colonies with characteristic morphology and staining gram-positive were confirmed as C difficile by membrane gas-chromatography.5 We used the ’Culturette’ rapid latex test (Marion Scientific) and followed the manufacturer’s guidelines carefully, the controls required being included. 84 C difficile latex agglutination positive samples, 29 culture positive samples (23 also positive on the latex test), and 17 negative samples in both tests were further studied by tissue cytotoxin assay.6 A cytopathic effect was confirmed by C sordellii antitoxin neutralisation. Samples, frozen at 40°C, were thawed and filtered just before assay, a procedure that does not result in loss of reactivity. 126 patients were admitted to the outbreak ward and 92 to the control ward. Upon admission 29% were positive by latex agglutination and 11 % by culture (table I). Diarrhoeal episodes were noted in 21 patients-14 were in the outbreak ward and 7 in the control ward; 11 were latex positive and 10 were culture positive (table i). Stool cultures of the diarrhoea patients revealed growth of no other intestinal bacterial or viral pathogen. 10 % of the 197 patients without diarrhoea were C difficile culture positive and 39% were latex agglutination positive. Both tests were positive in 5%. Of the 84 latex positive samples selected for further study 6 were positive in the cytotoxin assay (table II). The corresponding figure for culture-positive stools was 21%. The sensitivities of the latex test and culture were 100% but for specificity was only 23% and 77%, respectively, for an overall accuracy of 27% and 79%. Of the 218 patients 27% had had infections treated with an antimicrobial agent before admission or during the hospital stay. C difficile culture was positive or turned positive in 57% of the 59 antibiotic users but in only 8% of the 159 patients without antibiotic use. In the latex agglutination test the figures for antibiotic users and non-users were 54% and 35%, respectively. The finding of many false-positive C difficile latex tests among stool samples collected on geriatric wards has prompted us to reconsider our policy on antimicrobial treatment for C difficilerelated diseases. We used to give vancomycin or metronidazole to patients with diarrhoea who were latex agglutination positive, and patients were often isolated. We now use culture as a first-line test, because it is more specific than the latex test. Latex agglutination
first stool
sample was
admitted; 213
were
-
MICHAEL BECK
1. Bisler
H, Pfeiffer R, Klüken N, Pauschinger P. Wirkung von Roßkastaniensamenextrakt auf die transkapillare Filtration bei chronischer venoser Insuffizien. Dtsch Med Wochenschr 1986; 35: 1321. 2. Rudofsky G, Neiß A, Otto K, Seibel K. Ödemprotektive Wirkung und klinische Wirksamkeit von Roßkastaniensamenextrakt im Doppelblindversuch. Phlebol Proktol 1986; 15: 47. 3. Sterner M, Hillemanns HG. Untersuchung zur odemprotektiven Wirkung eines Venentherapeutikums. Munch Med Wochenschr 1986; 31: 551. 4 Marshall M, Dormandy JA. Oedema of long distant flights. Phlebology 1987; 2: 123. 5. Hitzenberger G. Die therapeutische Wirksamkeit des Roßkastaniensamenextraktes. Wien Med Wochenschr 1989; 17: 385.
False-positive Clostridium difficile latex agglutination tests SIR,-Clostridium difficile is responsible for pseudomembranous colitis and antibiotic-associated diarrhoea. C difficile-associated diseases are diagnosed by stool culture, by tissue culture for cytotoxin, and by a rapid latex agglutination test. All three tests have disadvantages. Culture detects all strains of C difficile, irrespective of toxin-producing capacity; the cytotoxin assay is widely accepted but is not standardised; and the latex test detects factors related to C difficile-associated diseases but not toxin A itself. 1,2 A combination of tests has been recommended3,.. but immediate decisions are usually made on the latex agglutination result. In April and May, 1988, there was an outbreak of diarrhoea on a geriatric ward in Turku City Hospital. We investigated all patients in the affected ward and in a control ward using routine culture techniques for all clinically important intestinal pathogens, including C difficile culture and latex-agglutination test. The wards did not differ with respect to the frequency of latex agglutinationpositive faecal samples (37% outbreak ward, 40% control ward) but C difficile cultures were positive at rates of 18% and 3%, respectively (p < 0-02). Most inpatients at the department of medicine, Turku City Hospital, are geriatric and long-stay. All patients admitted to the outbreak ward and a control ward from June to December, 1988, were investigated by C difficile culture and latex agglutination. The
or
during hospital stay
TABLE ll-CYTOTOXIN, LATEX, AND CULTURE RESULTS
