RECENT TRENDS IN THE MANAGEMENT OF ACUTE BACTERIAL MENINGITIS by nak14542

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									Editorial
                                                   corrhachia. Care must be taken to examine
                                                   the CSF soon after doing the LP as the cell
                                                   count tends to fall over a period of time and
                                                   may be falsely low after 30-60 min. The cell
RECENT TRENDS IN THE                               count is best done by manual methods as
MANAGEMENT OF ACUTE                                electronic cell counters are inaccurate
BACTERIAL MENINGITIS                               below counts of 1000 cells/cu mm. The nor-
                                                   mal CSF of children contains less than 6
                                                   WBC/ml and in 95%, there are no polymor-
                                                   phonuclear leukocytes(l). Thus, the pres-
                                                   ence of even a single polymorph may be
                                                   regarded as abnormal in a febrile child, to
                                                   initiate therapy pending the results of CSF
    Acute bacterial meningitis (ABM) con-
                                                   culture(2). In neonates the average WBC
tinues to be a major life-threatening illness
                                                   count in the CSF is 8/µ1 (range 0-32), 60%
in children. Although the introduction of
                                                   of which may be polymorphs(3). A CSF cell
new antimicrobial agents has had an impact,
                                                   count of >20/µl and/or polymorphs >5/µl
the outcome of meningitis has not improved
                                                   are considered abnormal(4). As there is a
appreciably. Recent research on animal
                                                   considerable overlap of all CSF indices be-
models has given a significant insight into -
                                                   tween infected and non-infected neonates, it
the pathogenesis which may, hopefully,
                                                   is ad\us4ble to treat whenever the CSF
lead to the development of innovative mo-
                                                   parameters are suggestive of ABM. It must
dalities for the management of meningitis.
                                                   be remembered, that in the early stages of
The management issues that currently con-
                                                   ABM, the CSF may be normal or may at
front us in our endeavour to reduce the mor-
                                                   times show lymphocytosis and also that cas-
bidity and mortality of ABM are: early
                                                   es of aseptic meningitis may have 30-90%
diagnosis, choice of initial antibiotics, use of
                                                   polymorphs in their initial CSF. A normal
adjunctive anti-inflammatory agents,
                                                   initial LP does not exclude ABM, and in the
effective supportive therapy including
                                                   presence of a strong clinical suspicion, it
role of fluid restriction and the role of neuro-
                                                   should be repeated few hours later.
imaging.
Diagnosis                                              Hypoglycorrhachia is present when CSF
                                                   glucose value is less than 50-60% of blood
    Prompt diagnosis is the cornerstone for
                                                   glucose in the older child and less than 75%
effective management. The clinical features
                                                   in the neonate. In any case, a CSF glucose
of meningitis are often non-specific, espe-
                                                   less than 40 mg/dl is considered definitive
cially in infants. A lumbar puncture (LP)
                                                   hypoglycorrhachia. Blood samples for glu-
performed at the earliest suspicion is, there-
                                                   cose estimation must be drawn before the
fore, important for making a presumptive
                                                   LP as the procedure may result in elevation
diagnosis and starting treatment. This is
                                                   of blood glucose levels.
based mainly on the finding of CSF poly-
morphonuclear leukocytosis and hypogly-                Gram stain of the CSF, if done properly
EDITORIAL


by an experienced person, is a highly sensi-          Culture results take at least 24-48 hours.
tive and specific, rapid and cheap bedside       Rapid diagnostic immunological tests are
diagnostic test. Fluorescent staining of bac-    useful for quick detection of bacterial anti-
terial DNA with acridine orange may show         gen or antibody even in partially treated
the bacterial morphology in cases where the      cases. The antigen does not disappear rapid-
Gram stain is negative(5).                       ly after killing of the bacteria, and may per-
                                                 sist for few days after antibiotic therapy.
    The LP may have to be withheld or                Latex particle agglutination (LPA),
delayed in children with signs of raised ICP     countercurrent        immunoelectrophoresis
and/or focal deficits because of the risk of     (CIEP), enzyme-linked immunosorbent as-
brain herniation. Control of intracranial        says (ELISA) and coagglutination (CO)
pressure (ICP), and a CT scan is required        tests detect bacterial antigen. The diagnostic
before doing the LP. Postponement of the         yield of these tests has been variably report-
LP is also indicated in children with hemo-      ed from 45-97%(7). It increases when the
dynamic instability, local infection at LP       CSF, blood and urine are examined con-
site, or DIC, until the conditions are man-      comitantly. The LPA is more sensitive than
aged and the procedure can be tolerated.         CIEP especially in detecting PRP antigen of
However, the treatment of ABM must be            H. influenzae b(2). However, false positive
started immediately, without waiting for the     results are not uncommon, and negative
LP. Administration of few doses of antibio-      results do not exclude meningitis. Specific
tics does not appreciably alter the results of   antibody detection tests are available for
the LP(2,5). The Gram stain and culture          anti PRP antibody of H. influenzae and IgM
positivity yield may however be reduced.         antibody to N. meningi-tidis Group A. The
As blood cultures reveal the bacterial patho-    Indian experience in this area is limit-
gen in >80% cases of untreated meningitis,       ed(7,9). The cost of these tests prohibits
these should be drawn before initiating anti-    their routine use in our country. They may
biotic therapy(2,5).                             have a useful role in partially treated cases
                                                 and where the Gram stain is negative.
    The definitive etiologic diagnosis of
meningitis is made by isolation of organ-        Antibiotic Therapy
isms from cultures of the CSF. Even a cyto-          It is imperative to start early and ade-
logically and biochemically normal CSF,          quate antibiotic therapy sometimes even be-
presumably done in the early stage of ABM,       fore the results of CSF examination become
may grow bacteria. Hence, culturing of all       available. The initial regimen has to be
CSF samples is important. A survey of            broad enough to affect all the likely patho-
ABM in our country revealed isolation of         gens anticipated according to the age of the
causative organisms in only 15.8%(6). The        child. Even though Gram stain smears or
causes of such a poor yield are non-avail-       immunological tests may indicate a specific
ability of CSF culture facilities round the      pathogen, broad-spectrum therapy is started
clock, delayed and faulty inoculation of         until results of culture and sensitivity are
CSF in culture media, and majority of cases      available.
having received antibiotics before hospital-
                                                 Birth to 3 months age
ization and LP. Some improvement in yield
can be achieved by direct plating of CSF.            In neonates a combination of penicillin

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INDIAN PEDIATRICS                                                 VOLUME 31-NOVEMBER 1994


and an aminoglycoside—generally ampicil-        resistant H. influenzae is rare in our country.
lin and gentamicin or amikacin have been        Chloramphenicol has the advantage that it
conventionally used. This has been based on     can be used orally after the initial 3-4 days
the bacteriological profile of ABM in this      of IV therapy, when the child can tolerate
age group as seen in Western countries.         oral feeds. It may be noted that a study from
This includes group B Streptococcus, Lis-       Delhi has found the use of chloramphenicol
teria monocytogenes and Gram negative           alone as initial therapy to be as effective as
pathogens. From the limited data available      the combination of penicillin and chloram-
from our country, Group B streptococcus         phenicol, with fewer side-effects(l0). Mul-
and Listeria are not significant pathogens      ticentric data are, however, needed before a
whereas Gram negative organisms are the         general recommendation can be made.
commonest(6). Ampicillin along with an          Newer Antibiotics
aminoglycoside has been an effective regi-
                                                    In developed countries, third generation
men. However, recently, due to the emerg-
                                                cephalosporins are now the preferred initial
ing resistance of Gram negative organisms
                                                antibiotics for meningitis. Both cefotaxime
to ampicillin, and reduced sensitivity to
                                                (150-200 mg/kg/day) and ceftriaxone (100
aminoglycosides, we have switched over to
                                                mg/kg/day) are effective against most of the
using a third generation cephalosporin
                                                bacteria causing meningitis, including mul-
either alone or in combination with amino-
                                                tiple resistant H. influenzae type b and peni-
glycosides. Cefotaxime is preferred in neo-
                                                cillin resistant pneumococcal strains(2,5).
nates, both because it has been used more
                                                The advantage of ceftriaxone is its once a
extensively and because it is not excreted by
                                                day dosage. Due to their cost, it may not be
the bile(2). Infants 1-3 months of age may
                                                possible to use them as first line antibiotics
have pathogens commonly encountered in
                                                in all cases of meningitis in our country.
the neonatal period or those seen beyond the
                                                They would, however be preferred in Gram
neonatal period. Indian data shows that
                                                negative ABM, and if affordability is not a
most cases of ABM in this age group also
                                                problem. Aztreonam, a synthetic monocylic
are caused by Gram negative organisms(6).
                                                B lactam antibiotic has also been shown to
Hence, the same regimen as for neonates is
                                                be effective against Gram negative patho-
recommended.
                                                gens, with good penetration into CSF.
Beyond 3 months of age                          Improvement in outcome has not yet been
                                                documented.
    The main causative organisms are me-
ningococcus, pneumococcus, and H. influ-            At times specific conditions or clinical
enzae; sometimes Gram negative bacilli and      clues towards specific organisms may war-
staphylococcus. H. influenzae is rarely seen    rant a change in the initial empiric therapy,
after 5 years of age. A combination of ampi-    viz., cover for staphylococcus in children
cillin 300-400 mg/kg/day (or penicillin         having meningitis with CSF shunts, and use
3,00,00 U/kg/day) and chloromycetin 75-         of ceftazidime for suspected pseudomonas
100 mg/kg/day has traditionally been used.      in nosocomial infections and immuno-
The use of ampicillin and chloromycetin         compromised children.
has been dictated by the need to cover H.       Subsequent Antibiotic Therapy
influenzae type b which may be resistant to
either one of these antibiotics. However,           Once the organism is isolated, specific

                                                                                          1323
EDITORIAL


antibiotic therapy can be used according to      reducing brain water content, CSF pressure,
its sensitivity. A minimum of 14-21 days         pleocytosis and lactate concentration, TNF
therapy is needed for neonates and 10-14         activity and other indices of meningeal in-
days for older infants and children. The         flammation has been proven in animal stud-
period may need to be extended as a result       ies(12) and has formed the basis of several
of complications.                                clinical trials. It is now recognized that
                                                 dexamethasone when used in the initial
    Repeat CSF examination either during,        stages of ABM, concomitantly with anti-
or prior to cessation of therapy, is not need-   biotics, reduces the incidence of neurologic
ed if the child responds appropriately. It       and/or audiologic sequelae of meningitis
should be done only if the clinical course       due to H. influenzae and probably also
indicates reason to doubt effectiveness of       pneumococcus(14,15). A dose of 0.15
therapy.                                         mg/kg of dexamethasone is given IV along-
Adjunctive Therapy                               with antibiotic administration, and repeated
                                                 every 6 hourly for 4 days. In the rare (<1%)
    An improved understanding of the             instance of gastrointestinal bleeding,
pathophysiology of meningitis(ll,12) has         steroids should be stopped(2).
focussed attention on non-antibiotic man-
                                                 Pentoxifylline
agement in search for a better outcome. Re-
search has shown that much of the cellular          This is a phosphodiesterase inhibitor
damage in meningitis results from the re-        which decreases adherence of leukocytes to
lease of toxic inflammatory mediators from       endothelial cells, reduces production of
macrophages, astrocytes and microglia in         superoxide and other toxic oxygen radicals
response to bacterial products and circulat-     and attenuates the release of proteolytic
ing endotoxin. CSF levels of endotoxin,          substances from neutrophils. It also sup-
interleukin (IL-1) and tumor necrosis factor     presses JNF production, and has been
(TNF) correlate with an adverse outcome. It      shown to reduce meningeal inflammation in
is of particular concern that levels rise        animals(16).
further following the administration of
antibiotics(13).                                     Non-steroidal anti-inflammatory agents
                                                 including indomethacin, monoclonal anti-
    The consequences of the inflammatory         bodies (anti-endotoxin, anti-TNF, anti-IL-
reaction, viz., severe cerebral edema, raised    IB, and anti-CD), oxygen radical scavengers
intracranial pressure, and reduced cerebral      and pharmacologic agents to modulate in-
blood flow (CBF) with loss of autoregula-        tracellular calcium flux are other areas of
tion further add to neuronal injury. It is       active research. Applicability of these mo-
hoped that severe and irreversible neuronal      dalities in human beings has yet to be estab-
injury may be prevented by modalities            lished. The use of human intravenous im-
directed at interrupting the inflammatory        munoglobulin may be important in neonates
cascade and timely correction of raised          and immune deficiency states.
ICP and cerebral edema.
                                                 Supportive Therapy
Steroids
                                                     This is particularly directed at control of
    The efficacy of dexamethasone in             raised ICP and seizures, and ensuring hemo-

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INDIAN PEDIATRICS                                                VOLUME 31-NOVEMBER 1994


dynamic and metabolic stability. Repeated          sequelae. Indeed, in experimental meningi-
evaluation during the first 48-72 hours is es-     tis in rabbits, fluid restriction has been
sential. A rapidly progressive or complicat-       shown to cause lowering of mean arterial
ed course, deep coma, intracranial hyperten-       blood pressure as well as cerebral blood
sion, shock or DIC warrant admission to the        flow and increase in CSF lactate(22).
Pediatric Intensive Care Unit (PICU), and              The last word on fluid administration
expeditious management 17). One of the             has yet to be said. It might be prudent to ad-
important issues currently under discussion        minister enough fluids to maintain normal
is that of fluid therapy.                          blood pressure and thereby achieve ade-
                                                   quate cerebral perfusion. All manipulations
Fluids                                             of fluids and electrolytes must be accompa-
                                                   nied by careful monitoring of the hydration
    The frequent occurrence of the syn-            status, hemodynamic variables, and plasma
drome of inappropriate secretion of antidi-        and urine electrolytes and osmolarity.
uretic hormone (SIADH) in meningitis has
led to the recommendation of giving re-            Role of Neuroimaging
stricted fluids during the initial stages of the
                                                       Ultrasonography in infants with open
disease(2,5). However, this concept is now
                                                   fontanelle is being increasingly used as an
being questioned. Powell et al. (18) assumed
                                                   important tool for early detection and moni-
that children with meningitis have hypovol-
                                                   toring of complications especially cerebral
emia, and should therefore receive normal
                                                   edema, and ventriculitis(23,24). It also has a
maintenance plus replacement fluids. This
                                                   therapeutic role in doing guided aspirations
was based on the finding that these patients
                                                   of ventricular fluid and brain abscesses, and
had high plasma arginine vasopressin
                                                   shunt placements. It may, however miss
(AVP) levels which rapidly normalized after
                                                   subdural effusions and infarcts(25). CT scan
IV administration of sodium and fluids
                                                   is needed where the sonographic findings
equal to 1.4 times maintenance require-
                                                   are doubtful. In older children, a CT is indi-
ments. However, no direct proof of hypo-
                                                   cated whenever the course is complicated,
volemia in meningitis has ever been pre-
                                                   viz, significant and persistent raised ICP,
sented. On the other hand it has been clearly
                                                   focal seizures or deficits, increasing head
shown that a majority of these patients have
                                                   circumference, and unexplained high and/or
increased body water and extracellular fluid
                                                   prolonged fever.
(ECW), which correlates with the severity
of the disease(19). At the same time, how-         Conclusions
ever, our studies have not shown any benefit
of fluid restriction on the outcome of men-            Management of meningitis warrants
ingitis, even in those with SIADH(20,21). It       immediate and appropriate antibiotic thera-
is possible that the increase in ECW is a          py, judicious use of dexamethasone, and
compensatory response to reduction in cere-        effective supportive therapy to control
bral flow and selective hypoperfusion of the       raised ICP and seizures. The traditional
cortex(19). Restriction of fluids could then       concept of fluid restriction needs re-exami-
have adverse effects on hemodynamic                nation. A consistent aggressive approach
stability and cerebral blood flow and              towards management of raised ICP and the
might lead to cerebral ischemia and more           use of therapeutic agents targeted against

                                                                                            1325
EDITORIAL


the inflammatory cascade are expected to                 Bacterial meningitis: Diagnosis by latex
improve the outcome of this serious disease.             agglutination test and clinical features.
                                                         Indian Pediatr 1993, 30: 495-500.
                        Pratibha D. Singhi,
                                                   10.   Kumar P, Verma IC. Antibiotic therapy
                       Additional Professor,             for bacterial meningitis in children in
                   Department of Pediatrics,             developing countries. Bull WHO 1993,
            Postgraduate Institute of Medical            71: 183-188.
                    Education and Research,
                                                   11.   Tunkel AR, Scheld WM. Pathogenesis
                       Chandigarh 160 012.               and pathophysiology of bacterial infec-
                                                         tions of the central nervous system. In:
REFERENCES                                               Infections of the Central Nervous System.
  1.   Portnoy JM, Olson LC. Normal cerebro-             Eds Scheld WM, Whitley RJ, Durack DT.
       spinal fluid values in children: Another          New York, Raven Press Ltd, 1991, pp
       look. Pediatrics 1985, 75: 484-487.               297-312.
  2.   Feigin RD, Me Cracken GH, Klein JO.         12.   Saez-Llorens X, Me Cracken GH.
       Diagnosis and management of meningitis.           Molecular pathophysiology of bacterial
       Pediatr Infect Dis J 1992, 11: 785-814.           meningitis. Recent Adv Pediatr 1993, 11:
                                                         93-106.
  3.   Sarff LD, Platt LH, Me Cracken GH. Ce-
       rebrospinal fluid evaluation in neonates.   13.   Arditi M, Abies L, Yoger R. Cerebrospi-
       Comparison of high risk infants with and          nal fluid endotoxin levels in children with
       without meningitis. J Pediatr 1976, 88:           H. influenzae meningitis before and after
       473-477.                                          administration of intravenous ceftriaxone.
                                                         J Infect Dis 1989, 160: 1005-1011.
  4.   Smith AL, Haas J. Neonatal bacterial
       meningitis. In: Infections of the Central   14.   Girchis NI, Farid Z, Mikhail IA, Farag I,
       Nervous System. Eds Scheld WM,                    Sultan Y. Dexamethasone treatment for
       Whitley RJ, Durack DT. New York,-                 bacterial meningitis in children and
       Raven Press Ltd, 1991, pp 313-333.                adults. Pediatr Infect Dis J 1989, 8: 848-
                                                         851.
  5.   Behrman RE. Acute bacterial meningitis
       beyond the neonatal period. In: Nelson      15.   Odio CM, Faingezicht I, Paris M, et al.
       Textbook of Pediatrics, 14th edn. Eds             The beneficial effects of early administra-
       Behrman RE, Kleigman RM, Nelson WE,               tion of dexamethasone in infants and chil-
       Vaughan VC. Philadelphia, WB Saunders             dren with bacterial meningitis. N Engl J
       Company, 1992, pp 683-691.                        Med 1991, 324: 1525-1531.
  6.   Kalra SK, Kumar P, Verma IC, et al. Bac-    16.   Sullivan GW, Carper HT, Novick WJ,
       terial meningitis in India: An UP survey.         Mandell GL. Inhibition of the inflamma-
       Indian J Pediatr 1991, 58: 505-511.               tory action of interleukin-1 and tumor ne-
                                                         crosis factor alpha on neutrophil function
  7.   Kalra     V.    Diagnostic tests for              by pentoxifylline. Infect Immun 1988, 56:
       meningitis—A dilemma. Indian Pediatr              1722-1729.
       1989,26: 1177-1180.
                                                   17.   Ackerman AD. Meningitis, infectious
  8.   Singh H, Safkar P, Sachdev HPS, Saini L.          encephalopathies, and other central ner-
       Immunological tests in bacterial menin-           vous system infections. In: Textbook of
       gitis. Indian Pediatr 1988, 25: 323-328.          Pediatric Intensive Care, 2nd edn. Ed
  9.   Deivanayagam     N,     Ashok      TP,            Rogers MC. Baltimore, Williams and
       Nedunchelian K, Ahamed SS, Mala N.                Wilkins, 1992, pp 1040-1083.

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INDIAN PEDIATRICS                                                          VOLUME 31-NOVEMBER 1994


 18.   Powell KR, Sugarman LI, Eskenazi AE, et             Child Neurology Society and the Inter-
       al. Normalization of plasma arginine                national Child Neurology Association,
       vasopressin concentrations when children            October 2-8, 1994, San Francisco, USA.
       with meningitis are given maintenance         22.   Tureen JH, Tauber MG, Sande MA. Ef-
       plus replacement fluid therapy. J Pediatr           fect of hydration status on cerebral blood
       1990, 117: 515-522.                                 flow and cerebrospinal fluid lactic acido-
 19.   Kumar V, Singhi P, Singhi S. Changes in             sis in rabbits with experimental menin-
       body water compartments in children with            gitis. J Clin Invest 1992, 89: 947-953.
       acute meningitis. Pediatric Infect Dis J      23.   Chowdhary V, Gulati P, Sachdev A,
       1994, 13: 299-305.                                  Mittal    SK.    Pyogenic   meningitis:
                                                           Sonographic evaluation. Indian Pediatr
 20.   Narakesari IIP, Kumar V. Fluid restric-
                                                           1991, 28: 749-755.
       tion in pyomeningitis. In: Conference
       Abstracts 1992. The Indian Academy of         24.   Talwar R, Talukdar B, Gupta NC, Rath B.
       Pediatrics, Eds Lokeshwar MR, Bhave                 Ultrasonographic study in meningitis.
       SY. Bombay, 1992, p 2.                              Indian Pediatr 1993, 30: 1225-1228.
 21.   Singhi P, Singhi S, Srinivas B, et al. Does   25.   Arrumugham R, Katariya S, Singhi P,
       fluid restriction improve the outcome of            Singhi S. Suri S, Walia BNS. Sonography
       acute meningitis? Paper accepted for pre-           in pyogenic meningitis. Indian Pediatr
       sentation at the Conjoint Meeting of the            1994, 1329-1336.




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