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The treatment of Bacterial Meningitis - A Reappraisal
Clinics in Neurology The Treatment of Bacterial Meningitis A Reappraisal
INTRODUCTION The introduction of sulphonamides in the late 1930's and penicillin and chloramphenicol in the early 1950's reduced dramatically the mortality of bacterial meningitis from 90% to 15% in the Western countries. However, in recent years there has been little evidence of further reduction despite the availability of an increasing number of antibiotics. Furthermore, among the survivors the incidence of major neurological sequelae has remained in the order of 30% (1). Indeed, current studies suggest that sensorineural deafness as an early and often irreversible complication may be unpreventable even by very early treatment of the meningitis (2). This paper examines the current opinions, puts on a Hong Kong perspective and delivers the author's personal strategy for treatment. EPIDEMIOLOGY Bacterial meningitis is not a single condition. The incidence, mortality and morbidity vary considerably according to the organism responsible. Knowledge of the factors predisposing meningitis can therefore be useful in the planning of treatment. Such factors include geographical location, age, social environment, presence of immunosuppression, co-existing disease or anatomical defect and history of trauma or neurosurgery. The overall epidemiological pattern of bacterial meningitis in Hong Kong differs significantly from that described in textbooks written for the Western countries The classical meningeal pathogens - Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae together account for 80 and 75% of all bacteria causing meningitis in the U.S.A. and U.K. respectively. In contrast, only S. pneumoniae retains such predominance (32%) in Hong Kong, both N. meningitidis and H. influenzae being relatively uncommon (10%) here. (Table 1) Two organisms (or groups of organisms) stand out in this locality as important meningeal pathogens. The first is Streptococcus suis which is now recognized as one of the most common causes of meningitis in adults (3, 4). The second consists of the Gram-negative bacilli which are three or four times more likely to cause meningitis here than in Britain or America. The emergence of S. suis has undoubtedly been due to increased recognition but the possible existence of nearby sources of infected pigs merits investigation. Local preponderance of Gram-negative meningitis is harder to explain. A survey of cases admitted to Queen Mary Hospital during 1983-6 (unpublished data) revealed that nearly all cases were associated with 'clinical antecedents' malignancy, steroid, overwhelming infection and old age. Other organisms tend to affect specific groups of patients, in Hong Kong as in elsewhere. Group B Streptococci cause meningitis almost exclusively in neonates; Staphylococci in patients with E.N.T. or neurosurgical conditions. Listeria favours the immunocompromised, but is also seen in previously healthy patients. The fungus, Cryptococcus neoformans, also behaves in this way and it is important to be aware of its not infrequent occurrence in Hong Kong.
Percentages of total
29 25 20 7 6 2 4 7
8 2 32 20* 4 5 10
48 20 13
4 1 2 1 5 6
Meningococcus Pneumococcus Streptococcus Staphylococcus
E. coli Others (mainly Gram-negatives)
* Including group B Streptococcus (10%) and Streptococcus suis (8%) ** Including Klebsiella (8%) and Pseudonomas (4%)
Table 1 Epidemiology of Bacterial Meningitis DIAGNOSIS Typical cases of acute bacterial meningitis present little problem in diagnosis. Approximately 80% of patients will have the classical triad of fever, stiff neck and altered consciousness, but this frequency is likely to be much lower in the very old and the very young. The definitive diagnosis rests on the lumbar puncture which should be performed "at the time it is thought of. Because the consequences of missing meningitis are so serious, it is axiomatic that "a normal spinal tap in a patient with clinically suspect meningitis is never cause for apology" (5). On the other hand, the question always arises as to whether it is safe to carry out the lumbar puncture for the fear of provoking herniation or 'coning' of the brain. Generally speaking, the
Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Bonham Road, Hong Kong Richard Kay, M.A., M.D., Senior Medical Officer Correspondence to: Dr. Richard Kay
Journal of the Hong Kong Medical Association Vol. 39, No. 3, 1987 risk is highest when there is raised intracranial pressure due to a mass lesion. C.T. scanning is the most sensitive method of detecting an intracranial mass and should be undertaken if access to it does not delay unduly the initiation of treatment. Otherwise, careful clinical evaluation is required. A mass lesion is suggested by sub-acute history, papilloedema and focal signs. Because of the diversity of organisms capable of causing meningitis, it is not recommended to omit lumbar puncture and institute treatment blindly which may well fail and endanger life. ANTIBIOTIC SELECTION Empirical therapy in meningitis is justified and necessary in two situations. The first is after the lumbar puncture but before the culture and sensitivity of the C.S.F. is known; the second is when bacterial meningitis is strongly suspected on the basis of C.S.F. leucocytosis and hypoglycorrachia, and yet the culture is negative. The selection of antibiotics empirically is based on local knowledge of the most likely pathogen considering the patient's age and immune status and whether the infection is community or hospital acquired or neurosurgically related. In Hong Kong, because of the prevalence of S. suis meningitis, the patient's occupation should be ascertained in order to determine if it brings the patient into contact with pigs, pork or pork-products in any way. Current recommendations as contained in the major textbooks (e.g. Oxford Textbook of Medicine, 1984; Harrison's Principle of Internal Medicine, 1987) usually quote ampicillin (or penicillin G) plus chloramphenicol (or gentamicin in the case of neonatal meningitis) as the first line treatment of meningitis of unknown etiology. This combination will adequately deal with S. pneumoniae, N. meningitidis and H. influenzae, but will not cover the Gramnegative bacilli unless gentamicin is actually used. Unfortunately, the poor lipid solubility of aminoglycosides limits their C.S.F. penetration, and nephrotoxicity and ototoxicity restrict the amount that can be given. In Hong Kong, as we have seen, the proportion of meningitis caused by Gram-negative bacilli may be as high as 30%. Empirical treatment here must therefore provide reliable cover against this group of organisms as well as, of course, the more classical pathogens. In this context, the newer (so-called third generation) cephalosporins appear to satisfy the demands of adequate C.S.F. penetration, potent bactericidal activity, low host toxicity and wide antimicrobial spectrum. Clinical trials (6) are beginning to show that these cephalosporins - particularly Cefotaxime (Claforan), Ceftriaxone (Rocephin) and Ceftazidime (Fortum) - are
Organism N. meningitidis S. pneumoniae and Other streptococci H. influenzae Antibiotic Penicillin G Penicillin G
effective in the treatment of meningitis caused by Gramnegative bacilli, while their activity against the more classical pathogens is about equivalent to ampicillin alone or in combination with chloramphenicol. While cephalosporins are not necessarily the drug of choice for certain known infections (e.g. they are ineffective against Listeria, unpredictable against Pseudonomas and unwanted against Staphylococci), it is likely that worldwide acceptance of their place in the empirical treatment of bacterial meningitis will follow once large-scale controlled trials have been completed. Definitive therapy replaces empirical treatment once the organism is identified and its sensitivity known. Table 2 lists the antibiotic regimens for the more common bacterial meningitis. Common and avoidable mistakes are found not as much as in the choice of antibiotics than in the dosage and duration given. The dosage must be large enough to ensure high C.S.F. drug concentrations and often this is several times the amount of the same drug one would normally give for the treatment of other less severe infections. The duration of therapy in meningitis should be at least 10 days for the classical pathogens and 3 weeks for the Gram-negative bacilli. Intravenous adminstration is mandatory and substitution of oral therapy once the patient becomes afebrile is not recommended. CONCLUSION The outcome of bacterial meningitis depends critically on early diagnosis and prompt treatment, and further reduction of current mortality and morbidity will have to come from improvements in the methods of detection as well as a reappraisal of therapeutic options. The newer cephalosporins appear to be appropriate alteratives for the empirical treatment of meningitis of unknown etiology in Hong Kong. They are also recommended for the majority of Gramnegative infections.
REFERENCES 1. Swartz MN. Bacterial meningitis: more involved than just the meninges. N. Engt J Med 1984; 311:912-914. 2. Dodge PR. Sequelae of bacterial meningitis. Paediatr Infect Dis 1986; 5:618-620. 3. Chau PY, Huang CY, Kay R. Streptococcus suis meningitis: an important underdiagnosed disease in Hong Kong. Med J Aust 1983; 1:414-417. 4. Oo KT, Chan J. The epidemic of group R streptococcal (Streptococcus suis) meningitis and septicaemia in Hong Kong. J Hong Kong Med Assoc 1985; 37:134136. 5. Levin S, Harris AA, Sokalski SJ. Bacterial meningitis. In: Vinken PJ, Bruyn GW (eds) Handbook of Clinical Neurology Vol. 33 1978, Amsterdam, North Holland; pp 1-19. 6. Whitby M, Finch R. Bacterial meningitis: rational selection and use of antibacterial drugs. Drugs 1986; 31:266-278.
IV dosage (mg/kg/day) 200,000 units 200,000 units
Chloramphenicol and/or Ampicillin Cloxacillin Cefotaxime or Ceftazidime
Staphylococcus Gram-negative bacilli
Table 2 Antibiotic regimens for bacterial meningitis of known etiology
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