Clinics in Neurology: The treatment of Bacterial Meningitis - A Reappraisal

Clinics in Neurology
The Treatment of Bacterial Meningitis
A Reappraisal
Richard Kay

INTRODUCTION preponderance of Gram-negative meningitis is harder to

The introduction of sulphonamides in the late 1930's and explain. A survey of cases admitted to Queen Mary Hospital
penicillin and chloramphenicol in the early 1950's reduced during 1983-6 (unpublished data) revealed that nearly all
dramatically the mortality of bacterial meningitis from 90% cases were associated with 'clinical antecedents' -
to 15% in the Western countries. However, in recent years malignancy, steroid, overwhelming infection and old age.
there has been little evidence of further reduction despite Other organisms tend to affect specific groups of
the availability of an increasing number of antibiotics. patients, in Hong Kong as in elsewhere. Group B
Furthermore, among the survivors the incidence of major Streptococci cause meningitis almost exclusively in
neurological sequelae has remained in the order of 30% (1). neonates; Staphylococci in patients with E.N.T. or
Indeed, current studies suggest that sensorineural deafness neurosurgical conditions. Listeria favours the immuno-
as an early and often irreversible complication may be compromised, but is also seen in previously healthy
unpreventable even by very early treatment of the patients. The fungus, Cryptococcus neoformans, also
meningitis (2). behaves in this way and it is important to be aware of its
This paper examines the current opinions, puts on a not infrequent occurrence in Hong Kong.
Hong Kong perspective and delivers the author's personal
strategy for treatment.
Percentages of total
Organism
EPIDEMIOLOGY U.K. U.S.A. H.K.
Bacterial meningitis is not a single condition. The 29 8
Haemophilus 48
incidence, mortality and morbidity vary considerably
according to the organism responsible. Knowledge of the Meningococcus 25 20 2
factors predisposing meningitis can therefore be useful in
the planning of treatment. Such factors include geographical Pneumococcus 20 13 32
location, age, social environment, presence of immuno- Streptococcus 7 4 20*
suppression, co-existing disease or anatomical defect and
history of trauma or neurosurgery. Staphylococcus 6 1 4
The overall epidemiological pattern of bacterial
Listeria 2 2 5
meningitis in Hong Kong differs significantly from that
described in textbooks written for the Western countries E. coli 4 1 10
The classical meningeal pathogens - Neisseria meningitidis,
Haemophilus influenzae and Streptococcus pneumoniae - Others (mainly Gram-negatives) 7 5 19**
together account for 80 and 75% of all bacteria causing Unknown 6
meningitis in the U.S.A. and U.K. respectively. In contrast,
only S. pneumoniae retains such predominance (32%) in * Including group B Streptococcus (10%) and Streptococcus suis (8%)
Hong Kong, both N. meningitidis and H. influenzae being ** Including Klebsiella (8%) and Pseudonomas (4%)
relatively uncommon (10%) here. (Table 1) Table 1 Epidemiology of Bacterial Meningitis
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 DIAGNOSIS
most common causes of meningitis in adults (3, 4). The Typical cases of acute bacterial meningitis present little
second consists of the Gram-negative bacilli which are three problem in diagnosis. Approximately 80% of patients will
or four times more likely to cause meningitis here than in have the classical triad of fever, stiff neck and altered
Britain or America. consciousness, but this frequency is likely to be much lower
The emergence of S. suis has undoubtedly been due to in the very old and the very young. The definitive diagnosis
increased recognition but the possible existence of nearby rests on the lumbar puncture which should be performed "at
sources of infected pigs merits investigation. Local 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
Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Bonham hand, the question always arises as to whether it is safe to
Road, Hong Kong carry out the lumbar puncture for the fear of provoking
Richard Kay, M.A., M.D., Senior Medical Officer
Correspondence to: Dr. Richard Kay herniation or 'coning' of the brain. Generally speaking, the

185
 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 Gram-
negative 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 Antibiotic
N. meningitidis Penicillin G
S. pneumoniae Penicillin G
and
Other streptococci
H. influenzae Chloramphenicol
and/or
Ampicillin
Staphylococcus Cloxacillin
Gram-negative bacilli Cefotaxime
or
Ceftazidime
Table 2 Antibiotic regimens for bacterial meningitis of known etiology
186
effective in the treatment of meningitis caused by Gram-
negative 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 cephalo-
sporins 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 Gram-
negative infections.
REFERENCES
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IV dosage (mg/kg/day) Frequency (hours)
200,000 units 3-4
200,000 units 3-6
100 6
150-200 3-4
200 4-6
150 8
150 8