525
EDITORIALS
Chemoprophylaxis for infective endocarditis:faith, hope,andcharity challenged The scientific basis for chemoprophylaxis of infective endocarditis remains controversiaP,2 Nobody doubts that the disease is life-threatening. Treatment of confirmed endocarditis (and confirmation may be difficult) is lengthy and may be complicated by drug toxicity. Surgery may be necessary for acute complications or to correct an underlying cardiovascular abnormality after recovery. Prevention is therefore a worthy objective. Strategies targeted at those at risk of the disease have largely emphasised the importance of good dental health and short-course chemoprophylaxis to protect against bacteraemia in relation to certain medical, surgical, and dental procedures. The use of chemoprophylaxis is based on several assumptions: (a) there should be a cardiovascular anomaly with a known risk of infection; (b) bacteraemia should be a recognised and frequent event following a defined procedure; and (c) target pathogens should be predictably susceptible to the proposed regimen, which in turn should be safe and effective in controlling bacteraemia. Assumptions favouring chemoprophylaxis have been supported by abundant experimental data in rabbit and rodent models of endocarditis, the drawbacks being the artificial nature of the challenge and use of a high inoculum of bacterial.3 In the past, recommendations for chemoprophylaxis were complex. Various regimens were promoted and the emphasis on parenteral agents limited compliance, especially with dental procedures.4 There has lately been a remarkable degree of international harmonisation among the recommended chemoprophylactic regimens from national organisations .5 Single high-dose amoxycillin
is recommended for most circumstances, with clindamycin or a two-dose erythromycin regimen for patients intolerant of penicillin. More complex parenteral schemes are still recommended for special risk patients--eg, those with a prosthetic valve undergoing general anaesthesia, those who have had a previous attack of endocarditis, and those who are allergic to penicillin or who have had penicillin more than once in the previous month and require a general anaesthetic. However, as noted in a Lancet editorial in 1976,6the exercise of chemoprophylaxis remains one of faith, hope, and charity. The hope is that endocarditis can be prevented through chemoprophylaxis; prevention has been hard to substantiate through clinical trials largely because of the logistic difficulties of recruiting enough patients with a defined cardiovascular risk undergoing a bacteraemia-inducing procedure which might, with faith, be protected by chemoprophylaxis. Most patients presenting with infective endocarditis have no obvious bacteraemia-inducing event and the calculated level of protection is probably less than of the International 10%.7 acceptance has been recommendations for chemoprophylaxis impressive, yet we still do not know for sure whether chemoprophylaxis is effective. In the 1990s, charity can no longer be dispensed by health care systems. Against this background van der Meer and colleagues8 lately challenged the conventional wisdom about chemoprophylaxis for prevention of nativevalve endocarditis. In a nationwide prospective study in the Netherlands, these researchers identified 438 documented cases of endocarditis over 2 years and selected 48 for study. These patients had native-valve or other cardiovascular abnormalities that increased their risk of getting endocarditis, and endocarditis had developed within 180 days of a defined medical or dental procedure for which chemoprophylaxis was indicated. Patients with prosthetic valves were not included since it is generally agreed that they have a much higher risk of endocarditis, often with catastrophic effects. Control subjects, matched for age but not sex, were selected from patients with similar cardiac lesions who did not get infective endocarditis but who had undergone a similar medical or dental procedure. Information about chemoprophylaxis was obtained by a carefully devised postal, telephone, and interview questionnaire system. On the assumption that symptoms would develop within 30 days of a procedure, the protective efficacy against first episodes of endocarditis was 49%. Dental root work and extractions seemed to carry a greater risk of endocarditis than did simple tooth scaling. Of the 438 patients with endocarditis, infection in 90% was unrelated to an identifiable medical or dental procedure, so the patients could not have benefited from chemoprophylaxis. This figure is a little higher than in some earlier series.9 Overall protective efficacy 7 was 6%, which accords with previous estimates.’ The researchers’ challenging conclusion is that
526
antibiotic prophylaxis for cardiac patients may not be cost-effective. This conclusion should be viewed in the light of prevailing medical practice in the Netherlands. The low compliance rate of 17% in a medically advanced society is a cause for concern and does not accord with other surveys with current regimens.1o The cost of widespread adoption of chemoprophylaxis has not been compared with the cost of treating an established case, and effects on the quality of life have not been defined. Another important issue in the aetiology of infective endocarditis is the dental health of the population; in countries that are less fortunate than the Netherlands in this respect the risk of endocarditis is likely to be higher. The biological properties of the causal pathogens are likewise important in any discussion of the efficacy of chemoprophylaxis for infective endocarditis. Bacteraemia is common in healthy people, whether or not they have cardiovascular abnormalities. Adherence to endocardial surfaces is an important attribute of many isolates responsible for infective endocarditis; among oral streptococci, dextranpositive strains are found more commonly among endocarditis isolates.11 The distribution of these organisms in the population at risk is another factor to be taken into account. Most expert groups have shied away from suggesting prospective controlled studies of the efficacy of chemoprophylaxis on the argument that it would require an impractically large population. Surely it is time for this negative view to be reassessed. The EC, with its 330 million inhabitants and advanced health care systems, might take the matter in hand. The doctrine of faith, hope, and charity may be a philosophy for life: it is no basis for perpetuating costly and possibly ineffective medical practices. Oakley CM. Controversies in the prophylaxis of infective endocarditis: a cardiological view. J Antimicrob Chemother 1987; 20 (suppl A): 99-104. 2. McGowan DA. A dental view of controversies in the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987; 20 (suppl A): 1.
105-09. 3. Glauser MP, Francioli P. Relevance of animal models to the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987; 20 (suppl A): 87-93. 4. Brooks SL. Survey of compliance with American Heart Association guidelines for prevention of bacterial endocarditis. J Am Dent Assoc 1980; 101: 41-43. 5. Finch R. Chemoprophylaxis of infective endocarditis. Scand J Infect Dis 1990; 70 (suppl): 102-10. 6. Editorial. Prophylaxis of bacterial endocarditis: faith, hope, and charitable interpretations. Lancet 1976; i: 519-20. 7. Durack DT. Prophylaxis of endocarditis. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. 3rd ed. New York: Churchill Livingstone, 1990: 716-21. 8. van der Meer JTM, van Wijk W, Vandenbroucke JP, Valkenburg HA,
Michel MF. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis: nationwide case-control study in the Netherlands. Lancet 1992; 339: 135-39. 9. Bayliss R, Clarke C, Oakley CM, Somerville W, Whitfield AGW, Young SEJ. The microbiology and pathogenesis of infective endocarditis. Br Heart J 1983; 50: 513-19. 10. Shanson DC. Antibiotic prophylaxis of infective endocarditis in the United Kingdom and Europe. J Antimicrob Chemother 1987; 20 (suppl A): 119-31. 11. Parker MT, Ball LC. Streptococci and aerococci associated with systemic infection in man. J Med Microbiol 1976; 9: 275-302.
Pertussis: adults, infants, and herds The diagnosis of pertussis is in serious danger of derailment at a time when its reliability is more important than ever. Despite increasing use of serology, the gold standard for laboratory diagnosis of pertussis is bacterial culture from nasopharyngeal swabs.l Contrary to popular belief, such cultures yield positive results in as many as 80% of cases,l provided specimen collection and laboratory techniques are optimum.2 A Swedish study found an isolation rate of
70%, even though the primary plates were incubated for only 5 days.3 In typical cases of pertussis, clinical diagnosis is usually reliable; not so with milder cases of less than 3 weeks’ duration,4 and especially with adults in whom a severe cough may be the only symptom. Spasmodic cough may be caused by viruses, so laboratory confirmation is necessary. Direct fluorescent antibody testing of nasopharyngeal secretions gives falsepositive results with antigenically related organisms5,6 and cannot be relied own.7 Likewise, the specificity serological tests for pertussis antibody in secretions and serum, used in many countries, averages only 65%.1 Thus only isolation of Bordetella pertussis from individuals with symptoms of whooping cough can be regarded as proof of infection.8 In adults, after the usual catarrhal phase, painful paroxysms of cough, whoop, vomiting and may last for many weeks, although atypical illness with only a persistent cough is more common. The chain of infection usually includes young children, and intervals of 1-3 weeks between dates of onset suggest transmission to or from parent or grandparent or hospital staff. An outbreak in a Wisconsin nursing home for elderly people was typical in that there were no children:9 38 residents and 8 employees were seropositive, but only 4 (all residents) were culturepositive. Better evidence of adult infection came from Sweden, where 174 (5%) of 3488 culture-positive patients were adults (median age 35 years).1° Monthly reports from the Public Health Laboratory Service in Britain have shown a steady incidence of pertussis in adults, although such cases comprise only a small minority of the total isolates from cases of whooping cough. Other reports give little or no evidence of
(Scotland,11 Finland," reliability and the Australia,13 Japan,14 USA15). Widespread silent transmission of pertussis in families was deduced from a small American study of 18 household contacts, only 1 of whom was culture-positive.16 Further alarm comes from the Gambia,i’ with the suggestion that, as the immunity of vaccinated infants wanes, "transmission between young adults is likely to be
diagnostic
intense".
Severe
-
cough (per-tussis), possibly provoked by pertussis toxin, facilitates survival of the host by clearing the airway after the ciliated epithelium has been damaged by other toxins. However, this is not merely a display of microbial compassion: the
EDITORIALS
Chemoprophylaxis for infective endocarditis:faith, hope,andcharity challenged The scientific basis for chemoprophylaxis of infective endocarditis remains controversiaP,2 Nobody doubts that the disease is life-threatening. Treatment of confirmed endocarditis (and confirmation may be difficult) is lengthy and may be complicated by drug toxicity. Surgery may be necessary for acute complications or to correct an underlying cardiovascular abnormality after recovery. Prevention is therefore a worthy objective. Strategies targeted at those at risk of the disease have largely emphasised the importance of good dental health and short-course chemoprophylaxis to protect against bacteraemia in relation to certain medical, surgical, and dental procedures. The use of chemoprophylaxis is based on several assumptions: (a) there should be a cardiovascular anomaly with a known risk of infection; (b) bacteraemia should be a recognised and frequent event following a defined procedure; and (c) target pathogens should be predictably susceptible to the proposed regimen, which in turn should be safe and effective in controlling bacteraemia. Assumptions favouring chemoprophylaxis have been supported by abundant experimental data in rabbit and rodent models of endocarditis, the drawbacks being the artificial nature of the challenge and use of a high inoculum of bacterial.3 In the past, recommendations for chemoprophylaxis were complex. Various regimens were promoted and the emphasis on parenteral agents limited compliance, especially with dental procedures.4 There has lately been a remarkable degree of international harmonisation among the recommended chemoprophylactic regimens from national organisations .5 Single high-dose amoxycillin
is recommended for most circumstances, with clindamycin or a two-dose erythromycin regimen for patients intolerant of penicillin. More complex parenteral schemes are still recommended for special risk patients--eg, those with a prosthetic valve undergoing general anaesthesia, those who have had a previous attack of endocarditis, and those who are allergic to penicillin or who have had penicillin more than once in the previous month and require a general anaesthetic. However, as noted in a Lancet editorial in 1976,6the exercise of chemoprophylaxis remains one of faith, hope, and charity. The hope is that endocarditis can be prevented through chemoprophylaxis; prevention has been hard to substantiate through clinical trials largely because of the logistic difficulties of recruiting enough patients with a defined cardiovascular risk undergoing a bacteraemia-inducing procedure which might, with faith, be protected by chemoprophylaxis. Most patients presenting with infective endocarditis have no obvious bacteraemia-inducing event and the calculated level of protection is probably less than of the International 10%.7 acceptance has been recommendations for chemoprophylaxis impressive, yet we still do not know for sure whether chemoprophylaxis is effective. In the 1990s, charity can no longer be dispensed by health care systems. Against this background van der Meer and colleagues8 lately challenged the conventional wisdom about chemoprophylaxis for prevention of nativevalve endocarditis. In a nationwide prospective study in the Netherlands, these researchers identified 438 documented cases of endocarditis over 2 years and selected 48 for study. These patients had native-valve or other cardiovascular abnormalities that increased their risk of getting endocarditis, and endocarditis had developed within 180 days of a defined medical or dental procedure for which chemoprophylaxis was indicated. Patients with prosthetic valves were not included since it is generally agreed that they have a much higher risk of endocarditis, often with catastrophic effects. Control subjects, matched for age but not sex, were selected from patients with similar cardiac lesions who did not get infective endocarditis but who had undergone a similar medical or dental procedure. Information about chemoprophylaxis was obtained by a carefully devised postal, telephone, and interview questionnaire system. On the assumption that symptoms would develop within 30 days of a procedure, the protective efficacy against first episodes of endocarditis was 49%. Dental root work and extractions seemed to carry a greater risk of endocarditis than did simple tooth scaling. Of the 438 patients with endocarditis, infection in 90% was unrelated to an identifiable medical or dental procedure, so the patients could not have benefited from chemoprophylaxis. This figure is a little higher than in some earlier series.9 Overall protective efficacy 7 was 6%, which accords with previous estimates.’ The researchers’ challenging conclusion is that
526
antibiotic prophylaxis for cardiac patients may not be cost-effective. This conclusion should be viewed in the light of prevailing medical practice in the Netherlands. The low compliance rate of 17% in a medically advanced society is a cause for concern and does not accord with other surveys with current regimens.1o The cost of widespread adoption of chemoprophylaxis has not been compared with the cost of treating an established case, and effects on the quality of life have not been defined. Another important issue in the aetiology of infective endocarditis is the dental health of the population; in countries that are less fortunate than the Netherlands in this respect the risk of endocarditis is likely to be higher. The biological properties of the causal pathogens are likewise important in any discussion of the efficacy of chemoprophylaxis for infective endocarditis. Bacteraemia is common in healthy people, whether or not they have cardiovascular abnormalities. Adherence to endocardial surfaces is an important attribute of many isolates responsible for infective endocarditis; among oral streptococci, dextranpositive strains are found more commonly among endocarditis isolates.11 The distribution of these organisms in the population at risk is another factor to be taken into account. Most expert groups have shied away from suggesting prospective controlled studies of the efficacy of chemoprophylaxis on the argument that it would require an impractically large population. Surely it is time for this negative view to be reassessed. The EC, with its 330 million inhabitants and advanced health care systems, might take the matter in hand. The doctrine of faith, hope, and charity may be a philosophy for life: it is no basis for perpetuating costly and possibly ineffective medical practices. Oakley CM. Controversies in the prophylaxis of infective endocarditis: a cardiological view. J Antimicrob Chemother 1987; 20 (suppl A): 99-104. 2. McGowan DA. A dental view of controversies in the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987; 20 (suppl A): 1.
105-09. 3. Glauser MP, Francioli P. Relevance of animal models to the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987; 20 (suppl A): 87-93. 4. Brooks SL. Survey of compliance with American Heart Association guidelines for prevention of bacterial endocarditis. J Am Dent Assoc 1980; 101: 41-43. 5. Finch R. Chemoprophylaxis of infective endocarditis. Scand J Infect Dis 1990; 70 (suppl): 102-10. 6. Editorial. Prophylaxis of bacterial endocarditis: faith, hope, and charitable interpretations. Lancet 1976; i: 519-20. 7. Durack DT. Prophylaxis of endocarditis. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. 3rd ed. New York: Churchill Livingstone, 1990: 716-21. 8. van der Meer JTM, van Wijk W, Vandenbroucke JP, Valkenburg HA,
Michel MF. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis: nationwide case-control study in the Netherlands. Lancet 1992; 339: 135-39. 9. Bayliss R, Clarke C, Oakley CM, Somerville W, Whitfield AGW, Young SEJ. The microbiology and pathogenesis of infective endocarditis. Br Heart J 1983; 50: 513-19. 10. Shanson DC. Antibiotic prophylaxis of infective endocarditis in the United Kingdom and Europe. J Antimicrob Chemother 1987; 20 (suppl A): 119-31. 11. Parker MT, Ball LC. Streptococci and aerococci associated with systemic infection in man. J Med Microbiol 1976; 9: 275-302.
Pertussis: adults, infants, and herds The diagnosis of pertussis is in serious danger of derailment at a time when its reliability is more important than ever. Despite increasing use of serology, the gold standard for laboratory diagnosis of pertussis is bacterial culture from nasopharyngeal swabs.l Contrary to popular belief, such cultures yield positive results in as many as 80% of cases,l provided specimen collection and laboratory techniques are optimum.2 A Swedish study found an isolation rate of
70%, even though the primary plates were incubated for only 5 days.3 In typical cases of pertussis, clinical diagnosis is usually reliable; not so with milder cases of less than 3 weeks’ duration,4 and especially with adults in whom a severe cough may be the only symptom. Spasmodic cough may be caused by viruses, so laboratory confirmation is necessary. Direct fluorescent antibody testing of nasopharyngeal secretions gives falsepositive results with antigenically related organisms5,6 and cannot be relied own.7 Likewise, the specificity serological tests for pertussis antibody in secretions and serum, used in many countries, averages only 65%.1 Thus only isolation of Bordetella pertussis from individuals with symptoms of whooping cough can be regarded as proof of infection.8 In adults, after the usual catarrhal phase, painful paroxysms of cough, whoop, vomiting and may last for many weeks, although atypical illness with only a persistent cough is more common. The chain of infection usually includes young children, and intervals of 1-3 weeks between dates of onset suggest transmission to or from parent or grandparent or hospital staff. An outbreak in a Wisconsin nursing home for elderly people was typical in that there were no children:9 38 residents and 8 employees were seropositive, but only 4 (all residents) were culturepositive. Better evidence of adult infection came from Sweden, where 174 (5%) of 3488 culture-positive patients were adults (median age 35 years).1° Monthly reports from the Public Health Laboratory Service in Britain have shown a steady incidence of pertussis in adults, although such cases comprise only a small minority of the total isolates from cases of whooping cough. Other reports give little or no evidence of
(Scotland,11 Finland," reliability and the Australia,13 Japan,14 USA15). Widespread silent transmission of pertussis in families was deduced from a small American study of 18 household contacts, only 1 of whom was culture-positive.16 Further alarm comes from the Gambia,i’ with the suggestion that, as the immunity of vaccinated infants wanes, "transmission between young adults is likely to be
diagnostic
intense".
Severe
-
cough (per-tussis), possibly provoked by pertussis toxin, facilitates survival of the host by clearing the airway after the ciliated epithelium has been damaged by other toxins. However, this is not merely a display of microbial compassion: the
