832
ing the patient with sodium and water until the blood-pressure recovers while angiotensin blockade is maintained unchanged.7
alertness in
narcoleptics or to improve cataplexy suggests that dopamine may not be of great importance in the regulation of the sleep-waking cycle or of loss of muscle tone in these patients. This is consistent with Jouvet’s hypothesis that noradrenaline rather than dopamine is the catecholamine mainly concerned in modulating the sleep-waking cycle. 10 The alerting effect of amphetamine is unlikely to result from an increase in the availability of dopamine at receptor sites in the brain. We thank Prof. J. Knoll, department of pharmacology, Semmelweis University of Medicine, Budapest, and the Chinoin Pharmaceutical firm for supplies of (-)-deprenyl.
University Department of Neurology, King’s College Hospital and Institute of Psychiatry, London SE5
M. SCHACHTER P. A. PRICE J. D. PARKES
necessary to normalise blood-pressure.8 Furthermore, reducing the dose of captopril will not prevent hypotensive episodes since even very small doses still inhibit angiotensin conversion. If hypotension occurs with captopril an effective and more rational therapy than dose reduction consists in repletare
J.
Lancet, 1974, i, 408. 2. Gavras, H., Brunner, H R., Gavras, I., Laragh, J. H. ibid. 1974, ii, 353. 3. Brunner, H. R., Gavras, H., Laragh, J. H. Progr. cardiovasc. Dis. 1974, 17, 87. 4. Posternak, L.,
HARALAMBOS GAVRAS
gentamicin remains which have Control measures hospital. problem proved successful in some previous outbreaks,1,2 including barrier nursing of all cases and restruction of co-trimoxazole usage, have failed to eradicate these resistant strains, although the prevalence of patient colonisation has been reduced. In this respect, our experience is similar to that of several other London hospitals where gentamicin-resistant klebsiellx are now endemic. Our situation is aggravated by a high readmission-rate of colonised patients. SIR,-Klebsiella
dence columns of The Lancet1,2 conerning the parenterally active angiotensin-converting-enzyme inhibitor SQ 20, 881. Both observations confirm the physiological concept that we have advocated for several years.3 Dependence of blood pressure on the renin-angiotensin system is largely determined by the concomitant state of sodium balance. Thus, a decrease in the total body sodium of a hypertensive patient can shift the blood-pressure from a renin-independent state to a situation of exquisite renin dependence. Similarly, maintenance of normal blood-pressure requires the pressor effect of the renin-angiotensin system only after sodium depletion. Atkinson’s patient lost 3-1kg in weight and his serumsodium fell to 123 mmol/1 and serum-potassium to 2.0mmol/l while on "conventional antihypertensive therapy" (details not given). Presumably, large doses of diuretics had been administered previously, but even if without such therapy the data strongly suggest that the patient was severely sodium depleted, whatever the cause may have been; thus serious hypotension after blockade of the renin-system should have been expected. Atkinson et al. state that captopril was started at a "low dose" of 25 mg. However, as we have shown,5 even 20 mg can almost completely block angiotensin-i conversion up to angiotensin-i doses of 160 ng/kg body-weight. As little as 2.5 mg captopril produced considerable inhibition. There is no clinical evidence that increasing the dose of captopril beyond 25 mg enhances its antihypertensive effect. Higher doses merely prolong the duration of converting-enzyme inhibition.6 Physicians using captopril to treat hypertension can avoid hypotension in their patients by remembering some simple rules. An antagonist of the renin system should not be administered to patients who might be sodium and/or volume depleted. Only after blockade of the renin system has been started should sodium depletion be introduced by adding diuretics, if
10. Jouvet, M., Pujol, J. F. Adv. Biochem. Psychopharm. 1974, 11, 191. 1 Duhme, D. W., Sancho, J., Athanasoulis, C., Haber, E., Koch-Weser,
BERNARD WAEBER
Thorndike Memorial Laboratories, Boston City Hospital, Boston, Massachusetts, U.S.A.
Brunner, H. R., Gavras, H., Brunner, D. B. Kidney Int. 1977, 11, 197. 5. Ferguson, R. K , Turini, G. A., Brunner, H. R , Gavras, H., McKinstry, D.N Lancet 1977, i, 775 6. Brunner, H. R , Gavras, H , Waeber, B , Kershaw, G. R., Tunni, G. A., Vukovich, R A., McKinstry, D. N., Gavras, I. Ann. intern. Med. 1979, 90, 19. 7. Brunner, H. R , Waeber, B., Wauters, J. P., Turini, G. A., McKinstry, D N., Gavras, H. Lancet 1971, ii, 704.
aerogenes resistant to
at our
a
SIR, The letter by Dr Atkinson and colleagues (March 10, 557) reminds us of an earlier exchange in the correspon-
they
HANS R. BRUNNER
1011 Lausanne, Switzerland
KLEBSIELLA CROSS-INFECTION WITH CAPSULAR SEROTYPES 68 AND 21
RATIONAL USE OF CAPTOPRIL p.
Department of Medicine, Centre Hospitalier Universitaire,
In the eleven months since March
105
1, 1978,
we
have detected
predominantly elderly males admitted forurological procedures. Male renal-transplant recipients sharing a ward with these patients were also frequently colonised, as were, to a lesser extent, female urological and renal patients sharing a similar ward. Resistant klebsiellx were most frequently isolated from the urinary tract,. 86 out of 105 primary isolations being from urine, but faecal carriage was common, new
cases,
and there were a few isolations from sputum, wound swabs, and peritoneal dialysis fluid. Septicaemia occurred in 2 patients and was thought to be a contributory factor to the death of 1 of these. Environmental sampling detected resistant klebsiellæ in a soaking tub for urinals, a plastic bucket, and a ward sluice mop, suggesting that modes of transfer other than hand carriage3 may have been important early in the outbreak. Antibiotic treatment was for the most part restricted to those patients who showed clinical signs or symptoms of infection, or in whom pyuria was present, but renal-transplant recipients received more aggressive therapy. The usual regimen was a week’s course of either amikacin or cefuroxime, cefuroxime being preferred where there was impaired renal function. Capsular serotyping of 51 isolates by Coventry Public Health Laboratory showed a preponderance of types 21 and 68, indicating a common source or cross-infection. 16 of the strains were type 68 (31%) although this type accounts for only 2-3% of random isolations. Type 21, which constitutes 15-20% of random isolations but which is also commonly implicated in hospital outbreaks, accounted for 58% in our series. Disc sensitivity testing of 8 type-21 strains and 6 type-68 strains by the comparative method, showed that while all strains were fully sensitive to cefoxitin, type-68 strains were resistant to cefuroxime with zone diameters of less than 12 mm compared with a zone of 22.8 mm diameter for the Escherichia coli control. Type 68 also differed from type 21 in its ability to ferment dulcitol. These preliminary findings suggest that cefoxitin is preferable to cefuroxime for the treatment of such infections, especially in life-threatening situations where antibiotic sensitivities are not available. C. J. NOBLE G. DOWN Dulwich Public Health Laboratory, S. CHAMBERS Dulwich Hospital, London SE22 8QF C. DULAKE Coventry Public Health Laboratory, Warwickshire Hospital, Coventry CV14FH
1. Curie, K., and others. J. Hyg. Camb. 1978, 80, 115 2. Forbes, L, and others.Med. J. Aust. 1977, i, 14. 3 Casewell, M., Phillips, I. Br. med. J. 1977, ii, 1315.
P.R. MORTIMER J. PALFBEYMAN
ing the patient with sodium and water until the blood-pressure recovers while angiotensin blockade is maintained unchanged.7
alertness in
narcoleptics or to improve cataplexy suggests that dopamine may not be of great importance in the regulation of the sleep-waking cycle or of loss of muscle tone in these patients. This is consistent with Jouvet’s hypothesis that noradrenaline rather than dopamine is the catecholamine mainly concerned in modulating the sleep-waking cycle. 10 The alerting effect of amphetamine is unlikely to result from an increase in the availability of dopamine at receptor sites in the brain. We thank Prof. J. Knoll, department of pharmacology, Semmelweis University of Medicine, Budapest, and the Chinoin Pharmaceutical firm for supplies of (-)-deprenyl.
University Department of Neurology, King’s College Hospital and Institute of Psychiatry, London SE5
M. SCHACHTER P. A. PRICE J. D. PARKES
necessary to normalise blood-pressure.8 Furthermore, reducing the dose of captopril will not prevent hypotensive episodes since even very small doses still inhibit angiotensin conversion. If hypotension occurs with captopril an effective and more rational therapy than dose reduction consists in repletare
J.
Lancet, 1974, i, 408. 2. Gavras, H., Brunner, H R., Gavras, I., Laragh, J. H. ibid. 1974, ii, 353. 3. Brunner, H. R., Gavras, H., Laragh, J. H. Progr. cardiovasc. Dis. 1974, 17, 87. 4. Posternak, L.,
HARALAMBOS GAVRAS
gentamicin remains which have Control measures hospital. problem proved successful in some previous outbreaks,1,2 including barrier nursing of all cases and restruction of co-trimoxazole usage, have failed to eradicate these resistant strains, although the prevalence of patient colonisation has been reduced. In this respect, our experience is similar to that of several other London hospitals where gentamicin-resistant klebsiellx are now endemic. Our situation is aggravated by a high readmission-rate of colonised patients. SIR,-Klebsiella
dence columns of The Lancet1,2 conerning the parenterally active angiotensin-converting-enzyme inhibitor SQ 20, 881. Both observations confirm the physiological concept that we have advocated for several years.3 Dependence of blood pressure on the renin-angiotensin system is largely determined by the concomitant state of sodium balance. Thus, a decrease in the total body sodium of a hypertensive patient can shift the blood-pressure from a renin-independent state to a situation of exquisite renin dependence. Similarly, maintenance of normal blood-pressure requires the pressor effect of the renin-angiotensin system only after sodium depletion. Atkinson’s patient lost 3-1kg in weight and his serumsodium fell to 123 mmol/1 and serum-potassium to 2.0mmol/l while on "conventional antihypertensive therapy" (details not given). Presumably, large doses of diuretics had been administered previously, but even if without such therapy the data strongly suggest that the patient was severely sodium depleted, whatever the cause may have been; thus serious hypotension after blockade of the renin-system should have been expected. Atkinson et al. state that captopril was started at a "low dose" of 25 mg. However, as we have shown,5 even 20 mg can almost completely block angiotensin-i conversion up to angiotensin-i doses of 160 ng/kg body-weight. As little as 2.5 mg captopril produced considerable inhibition. There is no clinical evidence that increasing the dose of captopril beyond 25 mg enhances its antihypertensive effect. Higher doses merely prolong the duration of converting-enzyme inhibition.6 Physicians using captopril to treat hypertension can avoid hypotension in their patients by remembering some simple rules. An antagonist of the renin system should not be administered to patients who might be sodium and/or volume depleted. Only after blockade of the renin system has been started should sodium depletion be introduced by adding diuretics, if
10. Jouvet, M., Pujol, J. F. Adv. Biochem. Psychopharm. 1974, 11, 191. 1 Duhme, D. W., Sancho, J., Athanasoulis, C., Haber, E., Koch-Weser,
BERNARD WAEBER
Thorndike Memorial Laboratories, Boston City Hospital, Boston, Massachusetts, U.S.A.
Brunner, H. R., Gavras, H., Brunner, D. B. Kidney Int. 1977, 11, 197. 5. Ferguson, R. K , Turini, G. A., Brunner, H. R , Gavras, H., McKinstry, D.N Lancet 1977, i, 775 6. Brunner, H. R , Gavras, H , Waeber, B , Kershaw, G. R., Tunni, G. A., Vukovich, R A., McKinstry, D. N., Gavras, I. Ann. intern. Med. 1979, 90, 19. 7. Brunner, H. R , Waeber, B., Wauters, J. P., Turini, G. A., McKinstry, D N., Gavras, H. Lancet 1971, ii, 704.
aerogenes resistant to
at our
a
SIR, The letter by Dr Atkinson and colleagues (March 10, 557) reminds us of an earlier exchange in the correspon-
they
HANS R. BRUNNER
1011 Lausanne, Switzerland
KLEBSIELLA CROSS-INFECTION WITH CAPSULAR SEROTYPES 68 AND 21
RATIONAL USE OF CAPTOPRIL p.
Department of Medicine, Centre Hospitalier Universitaire,
In the eleven months since March
105
1, 1978,
we
have detected
predominantly elderly males admitted forurological procedures. Male renal-transplant recipients sharing a ward with these patients were also frequently colonised, as were, to a lesser extent, female urological and renal patients sharing a similar ward. Resistant klebsiellx were most frequently isolated from the urinary tract,. 86 out of 105 primary isolations being from urine, but faecal carriage was common, new
cases,
and there were a few isolations from sputum, wound swabs, and peritoneal dialysis fluid. Septicaemia occurred in 2 patients and was thought to be a contributory factor to the death of 1 of these. Environmental sampling detected resistant klebsiellæ in a soaking tub for urinals, a plastic bucket, and a ward sluice mop, suggesting that modes of transfer other than hand carriage3 may have been important early in the outbreak. Antibiotic treatment was for the most part restricted to those patients who showed clinical signs or symptoms of infection, or in whom pyuria was present, but renal-transplant recipients received more aggressive therapy. The usual regimen was a week’s course of either amikacin or cefuroxime, cefuroxime being preferred where there was impaired renal function. Capsular serotyping of 51 isolates by Coventry Public Health Laboratory showed a preponderance of types 21 and 68, indicating a common source or cross-infection. 16 of the strains were type 68 (31%) although this type accounts for only 2-3% of random isolations. Type 21, which constitutes 15-20% of random isolations but which is also commonly implicated in hospital outbreaks, accounted for 58% in our series. Disc sensitivity testing of 8 type-21 strains and 6 type-68 strains by the comparative method, showed that while all strains were fully sensitive to cefoxitin, type-68 strains were resistant to cefuroxime with zone diameters of less than 12 mm compared with a zone of 22.8 mm diameter for the Escherichia coli control. Type 68 also differed from type 21 in its ability to ferment dulcitol. These preliminary findings suggest that cefoxitin is preferable to cefuroxime for the treatment of such infections, especially in life-threatening situations where antibiotic sensitivities are not available. C. J. NOBLE G. DOWN Dulwich Public Health Laboratory, S. CHAMBERS Dulwich Hospital, London SE22 8QF C. DULAKE Coventry Public Health Laboratory, Warwickshire Hospital, Coventry CV14FH
1. Curie, K., and others. J. Hyg. Camb. 1978, 80, 115 2. Forbes, L, and others.Med. J. Aust. 1977, i, 14. 3 Casewell, M., Phillips, I. Br. med. J. 1977, ii, 1315.
P.R. MORTIMER J. PALFBEYMAN
