987
that oestrogen therapy is cardioprotective,’ Isles et al grudgingly state that lower CHD rates "might be conferred by female sex hormones". Nevertheless, as they admit, raised cholesterol concentrations play only a minor part in the pathogenesis of CHD in women. They have ignored the fact that whereas oestrogen therapy reduces the risk of CHD by up to 50%,1 especially in women with coronary atheroma,2it lowers low-density lipoprotein cholesterol by only 5-9%.3 Furthermore, in ovariectomised monkeys fed an atherogenic diet oestrogens reduced the degree of coronary atheroma by about 30%, irrespective of cholesterol concentrations.4 Their advice, especially for women with a history of CHD, should therefore have included consideration of oestrogen therapy. Isles et al correctly underscore the inadvisability of extrapolating data from men to women, an aspect we have also emphasised.5,6 Women are haemodynamically younger than men by some 15 years. The question at issue is, what is the physiological basis of this difference? But there is a regrettable lack of data on this subject.6 Our studies show substantial cardiovascular differences between the sexes. Although peripheral (forearm) blood-flow increases with age in both men and women, the main increase in women takes place in the seventh decade, by contrast with an earlier but gradual increase in men; the trend is similar with vascular reactivity, which decreases with age. In premenopausal women, endogenous oestradiol concentrations correlate negatively with peripheral blood flow, an association that has not been reported for serum testosterone in men. On the other hand, exogenous oestradiol increases forearm flow (and cardiac output) in non-flushing women.7 In hypertensive adults, premenopausal women have a higher cardiac output and lower peripheral resistance than men; a difference not seen after the menopause.8 Studies of the precise circulatory differences between the sexes could therefore potentially prove more relevant to the elucidation of female cardiovascular superiority than "waiting for Godot", in the form of more trials of treatment of hypercholesterolaemia in women, as Isles et al advocate. Department of Endocrinology, Royal Free Hospital School of Medicine, London NW3 2QG, UK
1
JEAN GINSBURG STANLEY OKOLO PAUL HARDIMAN
Stampfner MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. ten-year follow-up from the Nurses’ Health Study. N Engl J Med 1991, 325: 756-62.
2. Sullivan JM, Zwaag RV, Hughes JP, et al. Estrogen replacement and coronary artery disease effect on survival in postmenopausal women Arch Intern Med 1990; 150:
2557-62. 3 Samisoe G Cardiovascular disease and lipid metabolism: the influence of HRT. Long-term HRT. perceptions and realities. Carnforth: Parthenon Publishing, 1991. 4 Koudy Williams J, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 1990; 81: 1680-87. 5 Ginsburg J, ed. The circulation in the female from the cradle to the grave. Camforth: Parthenon Publishing, 1989. 6 Ginsburg J. The menopause, hormone replacement therapy and the cardiovascular system. In: Burger H, Boulet M, eds. A portrait of the menopause: expert reports on medical and therapeutic strategies for the 1990s. Carnforth: Parthenon Publishing, 1991. 7. Ginsburg J, Hardiman P Cardiovascular effects of transdermal oestradiol in postmenopausal women. Ann NY Acad Sci 1990; 592: 424-25. 8 Messerli FH, Garavaglia GE, Schmieder RE, et al. Disparate cardiovascular findings in men and women with essential hypertension. Ann Intern Med 1987; 107: 158-61.
omental adipose tissues, which have a high turnover of free fatty acids and are drained by the portal vein, have been implicated in unfavourable risk patterns for CHD. Advice for women with respect to weight loss to lower their risk for cardiovascular disease may therefore be mainly dependent on their fat distribution. Department of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV Wageningen,
JACOB C. SEIDELL
Netherlands
1. Seidell
JC, Cigolini M, Charzewska J, et al. Fat distribution and gender differences in lipids m men and women from four European communities. Atherosclerosis 1991; 87: 203-10. 2. Freedman DS, Jacobsen SJ, Barboriak JJ, et al. Body fat distribution and male/female differences in lipids and lipoproteins. Circulation 1990; 81: 1498-03. 3. Ostlund RE, Staten M, Kohrt WM, Schultz J, Malley M. The ratio of waist-to-hip circumference, plasma insulin level, and glucose tolerance as independent predictors of HDL2 cholesterol in older adults. N Engl J Med 1990; 332: 229-33. 4. Larsson B, Bengtsson C, Björntorp P, et al. Is abdominal fat distribution a main explanation for the male/female difference in the risk of myocardial infarction? Int J Obesity 1990; 14 (suppl 2): 80. 5. Seidell JC, Oosterlee A, Thijssen MAO, et al. Assessment of intra-abdominal and subcutaneous fat: relation between anthropometry and computed tomography. Am J Clin Nutr 1987; 45: 7-13. 6. Bjomtorp P. "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493-97 serum
Coronary heart disease and dietary factors W R, 1’rofessor Ulbricht and Proiessor Southgate (Oct 19,
985) propose two indices, one of atherogenicity and one of thrombogenicity, to assess the effect of dietary fat on coronary heart disease (CHD). We have calculated these indices from 7-day weighed food intake records for 665 men aged 45-59 years in the Caerphilly Prospective Heart Disease Study.’Fatty-acid intakes were calculated with the aid of food composition tables3 together with data from manufacturers on the composition of spreading fats and cooking fats and oils. The mean (SD) atherogenicity index was 0-92 (0-20) and thrombogenicity index 1-27 (0-23). The two indices were positively associated with each other (r=0’87). Although there were differences in the numerators, intakes of the saturated fatty acids 14:0, 16:0, and 18:0 were strongly positively associated with each other (r 0-80 to 0-96). This is because their major food sources are p
=
similar. The main difference in the denominators is the greater emphasis on n-3 polyunsaturated fatty acids (PUFA) in the thrombogenicity index. However, intakes of these fatty acids are low in the British diet and therefore constitute a minor component of the index. The table shows that the contribution of the various fatty acids to the two indices was strikingly similar. The relation of 14:0 was somewhat stronger with the atherogenicity index than with the thrombogenicity index and n-3 PUFA were more strongly inversely related to the thrombogenicity index than to the atherogenicity index. However, the table also shows that there were very strong associations between both these indices and total saturated fatty acids (as a percentage of total fat and as a percentage RELATIONS BETWEEN FATTY-ACID INTAKES AND INDICES OF ATHEROGENICITY AND THROMBOGENICITY (PEARSON CORRELATION COEFFICIENTS)
SIR,-Dr Isles and colleagues conclude that smoking habits, blood pressure, serum cholesterol, body mass index, and social class
explain the differences in coronary mortality between men and women. They do briefly mention that indices of central obesity could have greater predictive power than body mass index for coronary heart disease (CHD). These indicators of fat distribution may also be especially relevant in the sex difference in CHD. We1 and others23 have shown that gender differences in HDL-cholesterol and serum triglyceride concentrations disappear after adjustment for differences in indices of fat distribution between men and women. In fact, a preliminary prospective study’ shows that the difference in incidence of CHD between men and women could be attributed to variations in fat distribution. At a specific weight and height men have more fat stored in their abdominal cavity5 than women. In particular, the mesenteric and
cannot
All correlation coefficients greater than 0 10
are
statistically significant
988
of energy) and with total PUFA. Hence, although these formulae take account of the latest research on the effects of individual fatty acids, the indices are unlikely to be better predictors of CHD risk than more simple approaches using total saturates, total polyunsaturates, or fatty fish consumption (the major source of n-33
PUFA). MRC Epidemiology Unit (South Wales), Llandougt Hospital, Penarth, South Glamorgan CF6 1XX, UK
A. M. FEHILY J. W. G. YARNELL J. PICKERING P. C. ELWOOD
Collaborative
1. Caerphilly and Speedwell Group. Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Commun Hlth 1984; 38: 259-62. 2. Fehily AM, Yamell JWG, Bolton CH, Butland BK. Dietary determinants of plasma lipids and lipoproteins: the Caerphilly Study. Eur J Clin Nutr 1988; 42: 405-13. 3. Paul AA, Southgate DAT, Russell J. First supplement to McCance and Widdowson’s The composition of foods. London: HM Stationery Office, 1980.
Atypical treatments for schizophrenia SIR,-Your Feb 1 editorial rightly cautions against overenthusiasm for unproven treatments for schizophrenia. Your comment, however, that between 5% and 10% of patients do not respond at all to neuroleptics is not accurate. The study to which fer1 showed that 6-5% of patients did not achieve discharge, yr v i is not the same at all. More useful is the widely cited figure o. oliound 25% of schizophrenic patients having significant symptoms on traditional neuroleptics.2 This represents a major clinical challenge and is a source of considerable distress to
patients. Clozapiae does not, as you state, seem to offer a 20% increase in benefit over other neuroleptics in poorly responsive patients. The study you cite3shows a significant response in a treatment-resistant group in 30% of those on clozapine and in only 4% of those on chlorpromazine. This benefit, shown by a 20% improvement in the brief psychiatric rating scale (BPRS), is not therefore universal. It is, however, important to realise that these modest benefits can result in considerable relief for quite a few patients whose symptoms have been a source of torment for many years.
Participating physicians were free to prescribe the antibiotic(s) thought most suitable for the empirical treatment of pneumonia. Of the 115 patients with a clinical diagnosis of pneumococcal pneumonia who were followed prospectively, 79 were treated with penicillins (G 6-18 megaunits, amoxycillin 3-8 g daily) and the remainder were given erythromycin, a cephalosporin, or both. No significant differences in outcome were found between patients treated with penicillins and those treated with other antibiotics. 5 patients died; 2 deaths were thought to be directly related to the respiratory infection. In none of these cases was a penicillinresistant pneumococcus isolated. 8 of the 23 confirmed cases were caused by penicillin-resistant strains (5 with MICs from z 12-1 mg/l ; 3 with MICs of 2 mg/I). No significant differences were found in terms of demography, predisposing factors, underlying disease, severity of pneumonia, or outcome between patients treated with penicillins and others. I patient with a penicillin-resistant pneumococcus (MIC 1 mg/1) died; he had been treated with cefotaxime plus erythromycin. 2 patients on erythromycin had worsening pneumonia and needle aspiration of the lung revealed erythromycin-resistant pneumococci (MIC > 8 mg/1) in both; they responded to beta-lactams. Penicillin seems to be effective in the treatment of community-
acquired pneumococcal pneumonia caused by penicillin-resistant strains with MICs up to 2 mg/l, when given to adults at doses of 12 or more megaunits daily. Less than 2% of all pneumococci are found to have MICs higher than 2 mg/1.1 Such highly resistant strains are significantly associated with identifiable risk factors4 and are frequently of nosocomial origin,s and only in those circumstances should penicillin be considered inadequate and other empirical antibiotic treatment selected. Our 2 recent erythromycin failures, coupled with the increasing incidence of erythromycin resistance in pneumococci (up to 20% in a French survey’) indicate the need for caution in the widespread use of macrolides in the community. Department of Medicine, Hospital de Mutua de Terrassa, University of Barcelona, 08221 Terrassa, Spain
CARLOS SÁNCHEZ RAMONA ARMENGOL JOSEP LITE ISABEL MIR JAVIER GARAU
Horton
Hospital, Epsom, Surrey KT19 8PS, UK
JONATHAN EVANS
1. Macmillan JF, Crow TJ, Johnson AL,
Johnstone EC. The Northwick Park Study of episodes of schizophrenia III: short term outcome in trial entrants and trial eligible patients. Br J Psychiatry 1986; 148: 128-33. 2. Davis JM, Casper R. Antipsychotic drugs: clinical pharmacology and therapeutic use. Drugs 1977; 14: 260-82. 3. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment resistant schizophrenic. Arch Gen Psychiatry 1988; 45: 784-96. first
Penicillin-resistant pneumococci and
community-acquired pneumonia Sip,—The prevalence of penicillin-resistant pneumococci in Spain is on the increase. In 1988, up to 37 8% of all blood and cerebrospinal fluid (CSF) isolates were reported to be resistant to penicillin (MIC 0 125 mg/1 or more).’ This prompted us to recommend other antimicrobials for pneumococcal infections in Spain, a policy disputed by others, who argue from in-vitro data that patients diagnosed with pneumococcal pneumonia should still be treated with this antibiotic provided that most cases are still caused by susceptible or only moderately resistant strains.2 We have followed up all 232 patients with community-acquired pneumonia seen in our hospital from February, 1989, to January, 1990. We have evaluated treatment with intravenous penicillin and outcome in those diagnosed on clinical grounds as having pneumococcal pneumonia that required hospital admission. Also, but retrospectively, we examined the results of treatment in all 23 confirmed cases of community-acquired pneumococcal pneumonia seen from January, .1988, to January, 1990; those diagnoses were confirmed by positive blood cultures (15), or by transthoracic needle aspiration (5), brush (1), or pleural fluid (1) sampling. 12 of these 23 patients were seen during the prospective study (a detailed ount is to be published3).
J, Fenoll A, Vicioso M, Muñoz R. Increase in resistance to penicillin m pneumococci in Spain. Lancet 1989; i: 735. 2. Manresa F, Dorca J, Linares J, Martin R, Pallares R. Empirical treatment of pneumococcal pneumonia in Spain. Lancet 1989; i: 1338-39. 3. Sánchez C, Mir I, Armengol R, Lite J, Garau J. Neumococos resistentes a la penicilina y la utilizatión empirica de penicilinas en el tratamiento de la neumonia aguda extrahospitalaria. Enf Inf Microbiol Clin (in press). 4. Nava JM, Bella F, Garau J, et al. Streptococcus pneumoniae invasive disease factors predictive of infection by penicillin-resistant strains. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (October, 1991, Chicago): abstr 1. Casal
1032. 5. Pallares R, Gudiol F, Linares J, et al. Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin resistant pneumococci. N Engl JMed 1987; 317: 18-22. 6. Buu-Hoi AY, Goldstein FW, Acar JF. A seventeeen-year epidemiological survey of antimicrobial resistance in pneumococci in two hospitals. J Antimicrob Chemother 1988; 22 (suppl B): 41-52.
Cholera
diagnosed in clinical laboratory by DNA hybridisation
S1R,-Cholera is one of eleven infections coming under Japanese legislation on communicable diseases. When a cholera case (ie, toxigenic Vibrio cholerae 01 infected) is reported to a regional public health centre the patient must be admitted to a reference hospital and isolated until V cholerae 01disappears from their stools.’ Those positive for non-toxigenic V cholerae 01are not subject to hospital isolation, because their disease will be milder. The accurate and rapid detection of toxigenic V cholerae 01is thus very important, both to the individual and to the public health care, in Japan. DNA hybridisation tests based on probes constructed from fragments of recombinant plasmids coding the gene for cholera toxin2-S or a similar toxin6,7 have been shown to be useful in molecular and in experimental work on the toxigenicity of V cholerae 01. However, these tests have not been applied in the clinical diagnostic laboratory.
epidemiology
that oestrogen therapy is cardioprotective,’ Isles et al grudgingly state that lower CHD rates "might be conferred by female sex hormones". Nevertheless, as they admit, raised cholesterol concentrations play only a minor part in the pathogenesis of CHD in women. They have ignored the fact that whereas oestrogen therapy reduces the risk of CHD by up to 50%,1 especially in women with coronary atheroma,2it lowers low-density lipoprotein cholesterol by only 5-9%.3 Furthermore, in ovariectomised monkeys fed an atherogenic diet oestrogens reduced the degree of coronary atheroma by about 30%, irrespective of cholesterol concentrations.4 Their advice, especially for women with a history of CHD, should therefore have included consideration of oestrogen therapy. Isles et al correctly underscore the inadvisability of extrapolating data from men to women, an aspect we have also emphasised.5,6 Women are haemodynamically younger than men by some 15 years. The question at issue is, what is the physiological basis of this difference? But there is a regrettable lack of data on this subject.6 Our studies show substantial cardiovascular differences between the sexes. Although peripheral (forearm) blood-flow increases with age in both men and women, the main increase in women takes place in the seventh decade, by contrast with an earlier but gradual increase in men; the trend is similar with vascular reactivity, which decreases with age. In premenopausal women, endogenous oestradiol concentrations correlate negatively with peripheral blood flow, an association that has not been reported for serum testosterone in men. On the other hand, exogenous oestradiol increases forearm flow (and cardiac output) in non-flushing women.7 In hypertensive adults, premenopausal women have a higher cardiac output and lower peripheral resistance than men; a difference not seen after the menopause.8 Studies of the precise circulatory differences between the sexes could therefore potentially prove more relevant to the elucidation of female cardiovascular superiority than "waiting for Godot", in the form of more trials of treatment of hypercholesterolaemia in women, as Isles et al advocate. Department of Endocrinology, Royal Free Hospital School of Medicine, London NW3 2QG, UK
1
JEAN GINSBURG STANLEY OKOLO PAUL HARDIMAN
Stampfner MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. ten-year follow-up from the Nurses’ Health Study. N Engl J Med 1991, 325: 756-62.
2. Sullivan JM, Zwaag RV, Hughes JP, et al. Estrogen replacement and coronary artery disease effect on survival in postmenopausal women Arch Intern Med 1990; 150:
2557-62. 3 Samisoe G Cardiovascular disease and lipid metabolism: the influence of HRT. Long-term HRT. perceptions and realities. Carnforth: Parthenon Publishing, 1991. 4 Koudy Williams J, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 1990; 81: 1680-87. 5 Ginsburg J, ed. The circulation in the female from the cradle to the grave. Camforth: Parthenon Publishing, 1989. 6 Ginsburg J. The menopause, hormone replacement therapy and the cardiovascular system. In: Burger H, Boulet M, eds. A portrait of the menopause: expert reports on medical and therapeutic strategies for the 1990s. Carnforth: Parthenon Publishing, 1991. 7. Ginsburg J, Hardiman P Cardiovascular effects of transdermal oestradiol in postmenopausal women. Ann NY Acad Sci 1990; 592: 424-25. 8 Messerli FH, Garavaglia GE, Schmieder RE, et al. Disparate cardiovascular findings in men and women with essential hypertension. Ann Intern Med 1987; 107: 158-61.
omental adipose tissues, which have a high turnover of free fatty acids and are drained by the portal vein, have been implicated in unfavourable risk patterns for CHD. Advice for women with respect to weight loss to lower their risk for cardiovascular disease may therefore be mainly dependent on their fat distribution. Department of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV Wageningen,
JACOB C. SEIDELL
Netherlands
1. Seidell
JC, Cigolini M, Charzewska J, et al. Fat distribution and gender differences in lipids m men and women from four European communities. Atherosclerosis 1991; 87: 203-10. 2. Freedman DS, Jacobsen SJ, Barboriak JJ, et al. Body fat distribution and male/female differences in lipids and lipoproteins. Circulation 1990; 81: 1498-03. 3. Ostlund RE, Staten M, Kohrt WM, Schultz J, Malley M. The ratio of waist-to-hip circumference, plasma insulin level, and glucose tolerance as independent predictors of HDL2 cholesterol in older adults. N Engl J Med 1990; 332: 229-33. 4. Larsson B, Bengtsson C, Björntorp P, et al. Is abdominal fat distribution a main explanation for the male/female difference in the risk of myocardial infarction? Int J Obesity 1990; 14 (suppl 2): 80. 5. Seidell JC, Oosterlee A, Thijssen MAO, et al. Assessment of intra-abdominal and subcutaneous fat: relation between anthropometry and computed tomography. Am J Clin Nutr 1987; 45: 7-13. 6. Bjomtorp P. "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493-97 serum
Coronary heart disease and dietary factors W R, 1’rofessor Ulbricht and Proiessor Southgate (Oct 19,
985) propose two indices, one of atherogenicity and one of thrombogenicity, to assess the effect of dietary fat on coronary heart disease (CHD). We have calculated these indices from 7-day weighed food intake records for 665 men aged 45-59 years in the Caerphilly Prospective Heart Disease Study.’Fatty-acid intakes were calculated with the aid of food composition tables3 together with data from manufacturers on the composition of spreading fats and cooking fats and oils. The mean (SD) atherogenicity index was 0-92 (0-20) and thrombogenicity index 1-27 (0-23). The two indices were positively associated with each other (r=0’87). Although there were differences in the numerators, intakes of the saturated fatty acids 14:0, 16:0, and 18:0 were strongly positively associated with each other (r 0-80 to 0-96). This is because their major food sources are p
=
similar. The main difference in the denominators is the greater emphasis on n-3 polyunsaturated fatty acids (PUFA) in the thrombogenicity index. However, intakes of these fatty acids are low in the British diet and therefore constitute a minor component of the index. The table shows that the contribution of the various fatty acids to the two indices was strikingly similar. The relation of 14:0 was somewhat stronger with the atherogenicity index than with the thrombogenicity index and n-3 PUFA were more strongly inversely related to the thrombogenicity index than to the atherogenicity index. However, the table also shows that there were very strong associations between both these indices and total saturated fatty acids (as a percentage of total fat and as a percentage RELATIONS BETWEEN FATTY-ACID INTAKES AND INDICES OF ATHEROGENICITY AND THROMBOGENICITY (PEARSON CORRELATION COEFFICIENTS)
SIR,-Dr Isles and colleagues conclude that smoking habits, blood pressure, serum cholesterol, body mass index, and social class
explain the differences in coronary mortality between men and women. They do briefly mention that indices of central obesity could have greater predictive power than body mass index for coronary heart disease (CHD). These indicators of fat distribution may also be especially relevant in the sex difference in CHD. We1 and others23 have shown that gender differences in HDL-cholesterol and serum triglyceride concentrations disappear after adjustment for differences in indices of fat distribution between men and women. In fact, a preliminary prospective study’ shows that the difference in incidence of CHD between men and women could be attributed to variations in fat distribution. At a specific weight and height men have more fat stored in their abdominal cavity5 than women. In particular, the mesenteric and
cannot
All correlation coefficients greater than 0 10
are
statistically significant
988
of energy) and with total PUFA. Hence, although these formulae take account of the latest research on the effects of individual fatty acids, the indices are unlikely to be better predictors of CHD risk than more simple approaches using total saturates, total polyunsaturates, or fatty fish consumption (the major source of n-33
PUFA). MRC Epidemiology Unit (South Wales), Llandougt Hospital, Penarth, South Glamorgan CF6 1XX, UK
A. M. FEHILY J. W. G. YARNELL J. PICKERING P. C. ELWOOD
Collaborative
1. Caerphilly and Speedwell Group. Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Commun Hlth 1984; 38: 259-62. 2. Fehily AM, Yamell JWG, Bolton CH, Butland BK. Dietary determinants of plasma lipids and lipoproteins: the Caerphilly Study. Eur J Clin Nutr 1988; 42: 405-13. 3. Paul AA, Southgate DAT, Russell J. First supplement to McCance and Widdowson’s The composition of foods. London: HM Stationery Office, 1980.
Atypical treatments for schizophrenia SIR,-Your Feb 1 editorial rightly cautions against overenthusiasm for unproven treatments for schizophrenia. Your comment, however, that between 5% and 10% of patients do not respond at all to neuroleptics is not accurate. The study to which fer1 showed that 6-5% of patients did not achieve discharge, yr v i is not the same at all. More useful is the widely cited figure o. oliound 25% of schizophrenic patients having significant symptoms on traditional neuroleptics.2 This represents a major clinical challenge and is a source of considerable distress to
patients. Clozapiae does not, as you state, seem to offer a 20% increase in benefit over other neuroleptics in poorly responsive patients. The study you cite3shows a significant response in a treatment-resistant group in 30% of those on clozapine and in only 4% of those on chlorpromazine. This benefit, shown by a 20% improvement in the brief psychiatric rating scale (BPRS), is not therefore universal. It is, however, important to realise that these modest benefits can result in considerable relief for quite a few patients whose symptoms have been a source of torment for many years.
Participating physicians were free to prescribe the antibiotic(s) thought most suitable for the empirical treatment of pneumonia. Of the 115 patients with a clinical diagnosis of pneumococcal pneumonia who were followed prospectively, 79 were treated with penicillins (G 6-18 megaunits, amoxycillin 3-8 g daily) and the remainder were given erythromycin, a cephalosporin, or both. No significant differences in outcome were found between patients treated with penicillins and those treated with other antibiotics. 5 patients died; 2 deaths were thought to be directly related to the respiratory infection. In none of these cases was a penicillinresistant pneumococcus isolated. 8 of the 23 confirmed cases were caused by penicillin-resistant strains (5 with MICs from z 12-1 mg/l ; 3 with MICs of 2 mg/I). No significant differences were found in terms of demography, predisposing factors, underlying disease, severity of pneumonia, or outcome between patients treated with penicillins and others. I patient with a penicillin-resistant pneumococcus (MIC 1 mg/1) died; he had been treated with cefotaxime plus erythromycin. 2 patients on erythromycin had worsening pneumonia and needle aspiration of the lung revealed erythromycin-resistant pneumococci (MIC > 8 mg/1) in both; they responded to beta-lactams. Penicillin seems to be effective in the treatment of community-
acquired pneumococcal pneumonia caused by penicillin-resistant strains with MICs up to 2 mg/l, when given to adults at doses of 12 or more megaunits daily. Less than 2% of all pneumococci are found to have MICs higher than 2 mg/1.1 Such highly resistant strains are significantly associated with identifiable risk factors4 and are frequently of nosocomial origin,s and only in those circumstances should penicillin be considered inadequate and other empirical antibiotic treatment selected. Our 2 recent erythromycin failures, coupled with the increasing incidence of erythromycin resistance in pneumococci (up to 20% in a French survey’) indicate the need for caution in the widespread use of macrolides in the community. Department of Medicine, Hospital de Mutua de Terrassa, University of Barcelona, 08221 Terrassa, Spain
CARLOS SÁNCHEZ RAMONA ARMENGOL JOSEP LITE ISABEL MIR JAVIER GARAU
Horton
Hospital, Epsom, Surrey KT19 8PS, UK
JONATHAN EVANS
1. Macmillan JF, Crow TJ, Johnson AL,
Johnstone EC. The Northwick Park Study of episodes of schizophrenia III: short term outcome in trial entrants and trial eligible patients. Br J Psychiatry 1986; 148: 128-33. 2. Davis JM, Casper R. Antipsychotic drugs: clinical pharmacology and therapeutic use. Drugs 1977; 14: 260-82. 3. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment resistant schizophrenic. Arch Gen Psychiatry 1988; 45: 784-96. first
Penicillin-resistant pneumococci and
community-acquired pneumonia Sip,—The prevalence of penicillin-resistant pneumococci in Spain is on the increase. In 1988, up to 37 8% of all blood and cerebrospinal fluid (CSF) isolates were reported to be resistant to penicillin (MIC 0 125 mg/1 or more).’ This prompted us to recommend other antimicrobials for pneumococcal infections in Spain, a policy disputed by others, who argue from in-vitro data that patients diagnosed with pneumococcal pneumonia should still be treated with this antibiotic provided that most cases are still caused by susceptible or only moderately resistant strains.2 We have followed up all 232 patients with community-acquired pneumonia seen in our hospital from February, 1989, to January, 1990. We have evaluated treatment with intravenous penicillin and outcome in those diagnosed on clinical grounds as having pneumococcal pneumonia that required hospital admission. Also, but retrospectively, we examined the results of treatment in all 23 confirmed cases of community-acquired pneumococcal pneumonia seen from January, .1988, to January, 1990; those diagnoses were confirmed by positive blood cultures (15), or by transthoracic needle aspiration (5), brush (1), or pleural fluid (1) sampling. 12 of these 23 patients were seen during the prospective study (a detailed ount is to be published3).
J, Fenoll A, Vicioso M, Muñoz R. Increase in resistance to penicillin m pneumococci in Spain. Lancet 1989; i: 735. 2. Manresa F, Dorca J, Linares J, Martin R, Pallares R. Empirical treatment of pneumococcal pneumonia in Spain. Lancet 1989; i: 1338-39. 3. Sánchez C, Mir I, Armengol R, Lite J, Garau J. Neumococos resistentes a la penicilina y la utilizatión empirica de penicilinas en el tratamiento de la neumonia aguda extrahospitalaria. Enf Inf Microbiol Clin (in press). 4. Nava JM, Bella F, Garau J, et al. Streptococcus pneumoniae invasive disease factors predictive of infection by penicillin-resistant strains. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (October, 1991, Chicago): abstr 1. Casal
1032. 5. Pallares R, Gudiol F, Linares J, et al. Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin resistant pneumococci. N Engl JMed 1987; 317: 18-22. 6. Buu-Hoi AY, Goldstein FW, Acar JF. A seventeeen-year epidemiological survey of antimicrobial resistance in pneumococci in two hospitals. J Antimicrob Chemother 1988; 22 (suppl B): 41-52.
Cholera
diagnosed in clinical laboratory by DNA hybridisation
S1R,-Cholera is one of eleven infections coming under Japanese legislation on communicable diseases. When a cholera case (ie, toxigenic Vibrio cholerae 01 infected) is reported to a regional public health centre the patient must be admitted to a reference hospital and isolated until V cholerae 01disappears from their stools.’ Those positive for non-toxigenic V cholerae 01are not subject to hospital isolation, because their disease will be milder. The accurate and rapid detection of toxigenic V cholerae 01is thus very important, both to the individual and to the public health care, in Japan. DNA hybridisation tests based on probes constructed from fragments of recombinant plasmids coding the gene for cholera toxin2-S or a similar toxin6,7 have been shown to be useful in molecular and in experimental work on the toxigenicity of V cholerae 01. However, these tests have not been applied in the clinical diagnostic laboratory.
epidemiology
