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Rapid diagnosis of tuberculous meningitis
334
Letters to the Editor
Rapid diagnosis of tuberculous meningitis Accepted for publication I4 October I99I Sir, Early detection and treatment of tuberculous meningitis ( T B M ) improves its outcome, 1 but investigations to support a clinical diagnosis have been unsatisfactory. T B M is u n c o m m o n in developed countries though it still occurs. 1 In our hospital we have had four cases (three adults, one child) during the last I5 years (I975-I99o). In all of these, Mycobacterium tuberculosis was eventually cultured from the cerebrospinal fluid (CSF) and in two, Ziehl-Nielsen (ZN) staining o f the C S F for acid fast bacilli (AFB) was positive. A high C S F lactate level (5"8 mmol/l) in one o f the latter suggested that the original diagnosis of viral meningitis was incorrect, and a prolonged examination of the C S F eventually revealed AFB. In another case, only post-mortem C S F grew M. tuberculosis after ante-mortem stains and cultures had been negative. These cases illustrate the difficulties that can be encountered in confirming a diagnosis of T B M . T h e diagnosis of T B M is established by identification of M. tuberculosis in Z N stained C S F in Io-4o % cases, and by C S F culture in 45-90 %.2 Various methods of increasing the positive yield of investigations in this condition have been recommended. Raised C S F lactate values may be a useful pointer to T B M . 3 T h e radioactive bromide partition test has been reported as having sensitivity and specificity of around 90 % / a n d has been found superior to E L I S A techniques (detecting antibody to M. tuberculosis antigen) and adenosine deaminase activity in a study of Coovadia et al. 4 Unfortunately the bromide partition test requires a gamma counter which limits its usefulness in developing countries. Better results of 99 % specificity for the adenosine deaminase test have been reported more recently2 E L I S A tests detecting antigen have varied in their specificity and the limitations o f reports published so far have been well summarised. ~ M o r e recently the use of the polymerase chain reaction (PCR) has been reported by Shankar et aL e T h e y compared the technique with E L I S A (antibodies) and bacteriological culture achieving sensitivities o f 75, 57 and 43 Yo respectively in clinically highly probable cases. A false positive rate of 6 % was attributed to crosscontamination of specimen and it was not clear whether the culture positive cases were also P C R positive. This new technique, which may apparently be adapted for use in developing countries, seems to offer great promise and merits further study. In conclusion, given the great importance of making an early diagnosis of T B M , we would suggest that a formal multicentre trial of the various methods mentioned above, in particular lactate, E L I S A (antigen), adenosine deaminase and PCR, should be undertaken. Until such a study has been performed the optimal test, or combination of tests, in this important clinical situation will remain unclear. * Departments of Child Health and t Pathology, East Glamorgan General Hospital, Church Village, Mid Glamorgan, U.K.
D. Cameron* B. M. Ansari* .7. M. H. Boycet
References 1. Molari A, Lefrock JL. Tuberculous meningitis. Med Clin North Am 1985; 69: 315-313. 2. Daniel TM. New approaches to the rapid diagnosis of tuberculous meningitis, ff Infect Dis 1987; I55: 599-6o2.
Letters to the Editor
335
3. Mandal BK, Dunbar EM, Hooper J, Parker L. How useful is cerebrospinal fluid lactate estimation in differential diagnosis of meningitis ? J Infect I983; 6: 231-237. 4. Coovadia YM, Dawood A, Ellis ME et al. Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculous antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculous meningitis. Arch Dis Child 1986; 61: 428-435. 5. Ribera E, Martinez-Vazquez JM, Ocana I et al. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis 1987; 155: 6o3-6o7. 6. Shankar P, Manjunath N, Moham K K et al. Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. Lancet I99I ; 337: 5-7.
Staphylococcus lusdunensis
endocarditis
Accepted for publication 20 November 1991 Sir,
Staphylococcus lugdunensis is a newly described species of coagulase-negative staphylococcus (C.N.S.). 1 Although the organism is less often associated with prosthetic valvular endocarditis than Staphylococcus epidermidisfl its potential virulence makes its differentiation from other C.N.S. essential. A 42-year-old w o m a n presented with malaise, sweating and arthralgia. Six months previously a prosthetic aortic valve had been implanted because of valvular damage sustained during an episode of Streptococcus viridans endocarditis. T h r e e months earlier she was in hospital for the investigation of fatigue and sweating. O n that occasion, two of eight blood cultures grew a C.N.S. which was not S. epidermidis and was considered to be a skin contaminant. Other investigations and clinical examination were normal. She was discharged f r o m hospital and attendance as an outpatient arranged. O t h e r noteworthy aspects of her medical history were longstanding p r i m a r y l y m p h o e d e m a of the legs and m a s t e c t o m y p e r f o r m e d 2 months before the most recent admission. At the time of mastectomy, benzylpenicillin and gentamicin were administered for 7 days. On examination, the patient was apyrexial, pulse rate i o o / m i n and blood pressure lO5/9o min. A systolic m u r m u r was audible in the aortic area. Roth's spots were noted and the spleen was palpable. An echocardiogram showed a normal prosthetic valve. One hour later her t e m p e r a t u r e was 39 ~ Blood for culture was drawn before treatment with benzylpenicillin, gentamicin and metronidazole began. On the following day, flucloxacillin was substituted for benzylpenicillin after a staphylococcus was detected in the blood cultures. Sensitivity of the organism to flucloxacillin and gentamicin was confirmed in vitro. T h e serum was bactericidial at a dilution > I in 32. Even so, a clinical response was not observed over a period of 5 days. Vancomycin was therefore substituted for gentamicin. Within 24 h the patient was afebrile and had symptomatically improved. Nevertheless, 16 days after her admission to hospital, acute left ventricular failure due to valvular dehiscence developed. She was transferred to another hospital and at an emergency operation pus was drained from the root of the aorta. T h e patient died soon afterwards. A haemolytic, DNAase-positive 3 staphylococcus was isolated f r o m all eight blood cultures. T h e tube-coagulase test applied to the organism was negative and its fermentation of maltose and trehalose indicated that it was not Staphylococcus epidermidis. 4 T h e Staphaurex test (Wellcome) was negative also. T h e Staphyslide test
Letters to the Editor
Rapid diagnosis of tuberculous meningitis Accepted for publication I4 October I99I Sir, Early detection and treatment of tuberculous meningitis ( T B M ) improves its outcome, 1 but investigations to support a clinical diagnosis have been unsatisfactory. T B M is u n c o m m o n in developed countries though it still occurs. 1 In our hospital we have had four cases (three adults, one child) during the last I5 years (I975-I99o). In all of these, Mycobacterium tuberculosis was eventually cultured from the cerebrospinal fluid (CSF) and in two, Ziehl-Nielsen (ZN) staining o f the C S F for acid fast bacilli (AFB) was positive. A high C S F lactate level (5"8 mmol/l) in one o f the latter suggested that the original diagnosis of viral meningitis was incorrect, and a prolonged examination of the C S F eventually revealed AFB. In another case, only post-mortem C S F grew M. tuberculosis after ante-mortem stains and cultures had been negative. These cases illustrate the difficulties that can be encountered in confirming a diagnosis of T B M . T h e diagnosis of T B M is established by identification of M. tuberculosis in Z N stained C S F in Io-4o % cases, and by C S F culture in 45-90 %.2 Various methods of increasing the positive yield of investigations in this condition have been recommended. Raised C S F lactate values may be a useful pointer to T B M . 3 T h e radioactive bromide partition test has been reported as having sensitivity and specificity of around 90 % / a n d has been found superior to E L I S A techniques (detecting antibody to M. tuberculosis antigen) and adenosine deaminase activity in a study of Coovadia et al. 4 Unfortunately the bromide partition test requires a gamma counter which limits its usefulness in developing countries. Better results of 99 % specificity for the adenosine deaminase test have been reported more recently2 E L I S A tests detecting antigen have varied in their specificity and the limitations o f reports published so far have been well summarised. ~ M o r e recently the use of the polymerase chain reaction (PCR) has been reported by Shankar et aL e T h e y compared the technique with E L I S A (antibodies) and bacteriological culture achieving sensitivities o f 75, 57 and 43 Yo respectively in clinically highly probable cases. A false positive rate of 6 % was attributed to crosscontamination of specimen and it was not clear whether the culture positive cases were also P C R positive. This new technique, which may apparently be adapted for use in developing countries, seems to offer great promise and merits further study. In conclusion, given the great importance of making an early diagnosis of T B M , we would suggest that a formal multicentre trial of the various methods mentioned above, in particular lactate, E L I S A (antigen), adenosine deaminase and PCR, should be undertaken. Until such a study has been performed the optimal test, or combination of tests, in this important clinical situation will remain unclear. * Departments of Child Health and t Pathology, East Glamorgan General Hospital, Church Village, Mid Glamorgan, U.K.
D. Cameron* B. M. Ansari* .7. M. H. Boycet
References 1. Molari A, Lefrock JL. Tuberculous meningitis. Med Clin North Am 1985; 69: 315-313. 2. Daniel TM. New approaches to the rapid diagnosis of tuberculous meningitis, ff Infect Dis 1987; I55: 599-6o2.
Letters to the Editor
335
3. Mandal BK, Dunbar EM, Hooper J, Parker L. How useful is cerebrospinal fluid lactate estimation in differential diagnosis of meningitis ? J Infect I983; 6: 231-237. 4. Coovadia YM, Dawood A, Ellis ME et al. Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculous antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculous meningitis. Arch Dis Child 1986; 61: 428-435. 5. Ribera E, Martinez-Vazquez JM, Ocana I et al. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis 1987; 155: 6o3-6o7. 6. Shankar P, Manjunath N, Moham K K et al. Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. Lancet I99I ; 337: 5-7.
Staphylococcus lusdunensis
endocarditis
Accepted for publication 20 November 1991 Sir,
Staphylococcus lugdunensis is a newly described species of coagulase-negative staphylococcus (C.N.S.). 1 Although the organism is less often associated with prosthetic valvular endocarditis than Staphylococcus epidermidisfl its potential virulence makes its differentiation from other C.N.S. essential. A 42-year-old w o m a n presented with malaise, sweating and arthralgia. Six months previously a prosthetic aortic valve had been implanted because of valvular damage sustained during an episode of Streptococcus viridans endocarditis. T h r e e months earlier she was in hospital for the investigation of fatigue and sweating. O n that occasion, two of eight blood cultures grew a C.N.S. which was not S. epidermidis and was considered to be a skin contaminant. Other investigations and clinical examination were normal. She was discharged f r o m hospital and attendance as an outpatient arranged. O t h e r noteworthy aspects of her medical history were longstanding p r i m a r y l y m p h o e d e m a of the legs and m a s t e c t o m y p e r f o r m e d 2 months before the most recent admission. At the time of mastectomy, benzylpenicillin and gentamicin were administered for 7 days. On examination, the patient was apyrexial, pulse rate i o o / m i n and blood pressure lO5/9o min. A systolic m u r m u r was audible in the aortic area. Roth's spots were noted and the spleen was palpable. An echocardiogram showed a normal prosthetic valve. One hour later her t e m p e r a t u r e was 39 ~ Blood for culture was drawn before treatment with benzylpenicillin, gentamicin and metronidazole began. On the following day, flucloxacillin was substituted for benzylpenicillin after a staphylococcus was detected in the blood cultures. Sensitivity of the organism to flucloxacillin and gentamicin was confirmed in vitro. T h e serum was bactericidial at a dilution > I in 32. Even so, a clinical response was not observed over a period of 5 days. Vancomycin was therefore substituted for gentamicin. Within 24 h the patient was afebrile and had symptomatically improved. Nevertheless, 16 days after her admission to hospital, acute left ventricular failure due to valvular dehiscence developed. She was transferred to another hospital and at an emergency operation pus was drained from the root of the aorta. T h e patient died soon afterwards. A haemolytic, DNAase-positive 3 staphylococcus was isolated f r o m all eight blood cultures. T h e tube-coagulase test applied to the organism was negative and its fermentation of maltose and trehalose indicated that it was not Staphylococcus epidermidis. 4 T h e Staphaurex test (Wellcome) was negative also. T h e Staphyslide test