MECILLINAM
1
864 have been reported in Mycoplasma infections.2 The impor- tance of the cold agglutinins often seen in Mycoplasma infec- tions is unknown. It is easy to imagine that invasion of the arterial-vessel wall by Mycoplasma may cause a lesion that leads to thrombosis either directly or secondarily to immunolo- gical reactions. Thrombocytosis and increased levels of coagu- lation factors may further contribute to thrombotic complica- tions. Venous thrombosis and disseminated intravascular coagula- tion are well-known complications of infection. The role of in- fection is less obvious in the development of arterial throm- bosis and needs further investigation. Department of Infectious Diseases, University of Lund, General Hospital, S-214 01 Malmö, Sweden BJÖRN ODE STIG CRONBERG MECILLINAM SIR,—Your editorial on mecillinam (Sept. 4, p. 503) states that "Large inocula of sensitive organisms have been found to contain highly resistant mutants." Since this statement has therapeutic implications, is attributed to us, and is untrue, may we put the record straight? Populations of gram-negative bacilli are heterogeneous with respect to internal osmotic pressure,3 4 and, since the lethal effect of s-lactam antibiotics (including mecillinam) is due to osmotic lysis of bacteria with weakened cell walls, those cells having an internal osmolality equal to or less than the environ- ment survive. Mecillinam lacks the ability of other -lactam antibiotics to inhibit bacterial division,5 so that bacteria sur- viving exposure to this antibiotic continue to multiply, albeit in a morphologically abnormal form.6 These multiplying sur- vivors are not mutants, but exhibit phenotypic resistance to mecillinam. The readiness with which such forms emerge depends on the osmotic milieu and the bacterial species. 7 8 In the absence of mecillinam the "resistant" bacteria reassume their normal shape and eventually, though not immediately, revert to normal susceptibility to mecillinam.6 It is possible that these "resistant" forms may not pose a therapeutic prob- lem because of their continuing morphological reactivity to mecillinam (such abnormal forms may be highly susceptible to host defences) and their slower growth-rate. Department of Microbiology, University of Nottingham, City Hospital, Nottingham NG5 1PH DAVID GREENWOOD FRANCIS O’GRADY PENICILLINASE-PRODUCING GONOCOCCI SIR,-Of the antimicrobial drugs you recommend (Oct. 2, p. 725) for treatment of gonorrhoea if penicillin therapy fails one is co-trimoxazole, and it will be interesting to see whether patients infected with such strains and so treated do respond. We have found that patients infected with gonococci rela- tively resistant to penicillin (minimum inhibitory concentra- tion>0.1 ug/ml) do not always respond to co-trimoxazole; in 17 of 43 such patients (39%) treatment failed compared with 1 failure in 58 patients infected with penicillin-sensitive 2. Biberfeld, G., Norberg, R J. Immun. 1974, 112, 413. 3 Greenwood, D., O’Grady, F. Br. J. exp. Path. 1972, 53, 457. 4. Scheie, P. J. Bact 1973, 114, 549. 5 Greenwood, D , O’Grady, F. J. infect. Dis. 1973, 128, 791. b. Greenwood, D., O’Grady, F. J clin. Path 1973, 26, 1. 7. Greenwood, D. Antimicrob. Ag. Chemother. (in the press). 8. Greenwood, D., Linton Brooks, H., Gargan, R., O’Grady, F. J clin. Path 1974, 27, 192. 9 Evans, A J., Churcher, G. M., Human, R. P. Br. J. vener Dis 1972, 48, 179. strains. The use of co-trimoxazole to treat all "penicillin :d. lures," as you suggest, may therefore not be advisable. Plymouth General Hospital Plymouth PL4 8QQ A. J. EVANS G. M. CHURCHER CORONARY-ARTERY SPASM AND MITRAL-VALVE PROLAPSE SIR,—DR Day and Dr Sowton (Aug. 14, p. 334) have d; scribed the clinical features and excellent prognosis of patients. with angina-like chest pain and normal coronary arteria They conclude that the cause of the symptoms in most of the,, patients has yet to be defined. Of particular interest IS the observation that 2 of the 45 patients exhibited coronary-artery spasm during cardiac catheterisation, a higher frequency thar has previously been reported for this procedure. 1 In a similar study, we examined the records of all patient undergoing cardiac catheterisation at our institution, and 8 in- dividuals with otherwise normal coronary arteries were found to have coronary-artery spasm. A review of the ventriculo- grams by independent observers revealed that 7 of these 8 pa- tients also had definite prolapse of one or more scallops of the mitral valve. 2 additional patients with single 50% lesions and proximal spasm in another vessel also had mitral-valve pro- lapse. In 8 of the 10 cases, the spasm was proximal and seemed to be catheter induced; 1 patient had spontaneous (distal spasm and another exhibited both types of spasm. Consider- ing how uncommon spasm and prolapse are it is surprising to find them together in the same patient. Of equal interest is the observation that intravenous phento- lamine, an alpha-adrenoceptor antagonist, abolished the proximal right-coronary-artery spasm in 2 of these panents.2 Mitral-valve prolapse and coronary-artery spasm’ hate been associated with chest pain in people free of coronan- artery disease. The finding of both prolapse and spasm in the same individuals suggests that the symptoms in some cases of mitral-valve prolapse may be the result of transient corona vasoconstriction. Although this hypothesis is attractive, a cau- sal link between these two conditions has not been established, The coincidence of spasm and prolapse could also be explained by a common pathogenetic factor-namely, abnormal alpha- adrenoceptor sensitivity. This explanation is supported by am- mal studies in which large coronary arteries have been shown to constrict in response to alpha-adrenoceptor stimulation. The demonstration that intravenous phenylephrine, an alpha- adrenoceptor agonist, may provoke chest pain in patients with mitral-valve prolapse5 suggests that this event could also h, mediated by these receptors. Since we have studied relatively few patients, further inves- tigations will be needed to determine the existence and nature of any association between coronary-artery spasm and miral- valve prolapse. Meanwhile, it would be interesting to knoBB th: incidence of valve prolapse of Day and Sowton’s series since mitral-valve prolapse is frequently found in patients with ches pain without demonstrable coronary disease. Division of Cardiology, Sunnybrook Hospital, Toronto, Ontario, Canada M4N 3M5 M. G. MYERS A. J. BUDA D. L. LEVENE A. W. CHISHOLM S. J. SHANE 1 Chahine, R A., Raizner, A. E., Ishimori, T., Luchi, R. J., Mclntosh, H. D. Circulation, 1975, 52, 972. 2. Levene, D L., Myers, M G. Can med. Ass. J. 1974, 111, 647. 3 Aranda, J. M , Befeler, B., El-Sherif, N., Castellanos, A, Lazzara, R. Am. J Med., 1976, 60, 997 4 Vatner, S. F., Millard, R W., Higgins, C. B. J. Pharmac. exp. Ther. 1973, 187, 280. 5. LeWinter, M. M., Hoffman, J. R., Shell, W. E., Karliner, J S., O’Rourke, R A Am J Cardiol 1974. 34, 12.
Transcript of MECILLINAM
864
have been reported in Mycoplasma infections.2 The impor-tance of the cold agglutinins often seen in Mycoplasma infec-tions is unknown. It is easy to imagine that invasion of thearterial-vessel wall by Mycoplasma may cause a lesion thatleads to thrombosis either directly or secondarily to immunolo-gical reactions. Thrombocytosis and increased levels of coagu-lation factors may further contribute to thrombotic complica-tions.
Venous thrombosis and disseminated intravascular coagula-tion are well-known complications of infection. The role of in-fection is less obvious in the development of arterial throm-bosis and needs further investigation.Department of Infectious Diseases,University of Lund,General Hospital,S-214 01 Malmö, Sweden
BJÖRN ODESTIG CRONBERG
MECILLINAM
SIR,—Your editorial on mecillinam (Sept. 4, p. 503) statesthat "Large inocula of sensitive organisms have been found tocontain highly resistant mutants." Since this statement hastherapeutic implications, is attributed to us, and is untrue,may we put the record straight?
Populations of gram-negative bacilli are heterogeneous withrespect to internal osmotic pressure,3 4 and, since the lethaleffect of s-lactam antibiotics (including mecillinam) is due toosmotic lysis of bacteria with weakened cell walls, those cellshaving an internal osmolality equal to or less than the environ-ment survive. Mecillinam lacks the ability of other -lactamantibiotics to inhibit bacterial division,5 so that bacteria sur-viving exposure to this antibiotic continue to multiply, albeitin a morphologically abnormal form.6 These multiplying sur-vivors are not mutants, but exhibit phenotypic resistance tomecillinam. The readiness with which such forms emergedepends on the osmotic milieu and the bacterial species. 7 8 Inthe absence of mecillinam the "resistant" bacteria reassumetheir normal shape and eventually, though not immediately,revert to normal susceptibility to mecillinam.6 It is possiblethat these "resistant" forms may not pose a therapeutic prob-lem because of their continuing morphological reactivity tomecillinam (such abnormal forms may be highly susceptible tohost defences) and their slower growth-rate.Department of Microbiology,University of Nottingham,City Hospital,Nottingham NG5 1PH
DAVID GREENWOODFRANCIS O’GRADY
PENICILLINASE-PRODUCING GONOCOCCISIR,-Of the antimicrobial drugs you recommend (Oct. 2,
p. 725) for treatment of gonorrhoea if penicillin therapy failsone is co-trimoxazole, and it will be interesting to see whetherpatients infected with such strains and so treated do respond.We have found that patients infected with gonococci rela-tively resistant to penicillin (minimum inhibitory concentra-tion>0.1 ug/ml) do not always respond to co-trimoxazole; in17 of 43 such patients (39%) treatment failed compared with1 failure in 58 patients infected with penicillin-sensitive
2. Biberfeld, G., Norberg, R J. Immun. 1974, 112, 413.3 Greenwood, D., O’Grady, F. Br. J. exp. Path. 1972, 53, 457.4. Scheie, P. J. Bact 1973, 114, 549.5 Greenwood, D , O’Grady, F. J. infect. Dis. 1973, 128, 791.b. Greenwood, D., O’Grady, F. J clin. Path 1973, 26, 1.7. Greenwood, D. Antimicrob. Ag. Chemother. (in the press).8. Greenwood, D., Linton Brooks, H., Gargan, R., O’Grady, F. J clin. Path
1974, 27, 192.9 Evans, A J., Churcher, G. M., Human, R. P. Br. J. vener Dis 1972, 48,
179.
strains. The use of co-trimoxazole to treat all "penicillin :d.lures," as you suggest, may therefore not be advisable.
Plymouth General HospitalPlymouth PL4 8QQ
A. J. EVANSG. M. CHURCHER
CORONARY-ARTERY SPASM AND MITRAL-VALVEPROLAPSE
SIR,—DR Day and Dr Sowton (Aug. 14, p. 334) have d;scribed the clinical features and excellent prognosis of patients.with angina-like chest pain and normal coronary arteria
They conclude that the cause of the symptoms in most of the,,patients has yet to be defined. Of particular interest IS theobservation that 2 of the 45 patients exhibited coronary-arteryspasm during cardiac catheterisation, a higher frequency tharhas previously been reported for this procedure. 1
In a similar study, we examined the records of all patientundergoing cardiac catheterisation at our institution, and 8 in-dividuals with otherwise normal coronary arteries were foundto have coronary-artery spasm. A review of the ventriculo-
grams by independent observers revealed that 7 of these 8 pa-tients also had definite prolapse of one or more scallops of themitral valve. 2 additional patients with single 50% lesions andproximal spasm in another vessel also had mitral-valve pro-lapse. In 8 of the 10 cases, the spasm was proximal and seemedto be catheter induced; 1 patient had spontaneous (distalspasm and another exhibited both types of spasm. Consider-
ing how uncommon spasm and prolapse are it is surprising tofind them together in the same patient.Of equal interest is the observation that intravenous phento-
lamine, an alpha-adrenoceptor antagonist, abolished the
proximal right-coronary-artery spasm in 2 of these panents.2Mitral-valve prolapse and coronary-artery spasm’ hate
been associated with chest pain in people free of coronan-artery disease. The finding of both prolapse and spasm in thesame individuals suggests that the symptoms in some cases ofmitral-valve prolapse may be the result of transient coronavasoconstriction. Although this hypothesis is attractive, a cau-sal link between these two conditions has not been established,The coincidence of spasm and prolapse could also be explainedby a common pathogenetic factor-namely, abnormal alpha-adrenoceptor sensitivity. This explanation is supported by am-mal studies in which large coronary arteries have been shownto constrict in response to alpha-adrenoceptor stimulation. Thedemonstration that intravenous phenylephrine, an alpha-adrenoceptor agonist, may provoke chest pain in patients withmitral-valve prolapse5 suggests that this event could also h,mediated by these receptors.
Since we have studied relatively few patients, further inves-tigations will be needed to determine the existence and natureof any association between coronary-artery spasm and miral-valve prolapse. Meanwhile, it would be interesting to knoBB th:incidence of valve prolapse of Day and Sowton’s series since
mitral-valve prolapse is frequently found in patients with chespain without demonstrable coronary disease.
Division of Cardiology,Sunnybrook Hospital,Toronto, Ontario, Canada M4N 3M5
M. G. MYERSA. J. BUDAD. L. LEVENEA. W. CHISHOLMS. J. SHANE
1 Chahine, R A., Raizner, A. E., Ishimori, T., Luchi, R. J., Mclntosh, H. D.
Circulation, 1975, 52, 972.2. Levene, D L., Myers, M G. Can med. Ass. J. 1974, 111, 647.3 Aranda, J. M , Befeler, B., El-Sherif, N., Castellanos, A, Lazzara, R. Am.
J Med., 1976, 60, 9974 Vatner, S. F., Millard, R W., Higgins, C. B. J. Pharmac. exp. Ther. 1973,
187, 280.5. LeWinter, M. M., Hoffman, J. R., Shell, W. E., Karliner, J S., O’Rourke,
R A Am J Cardiol 1974. 34, 12.
