Neonates: ampicillin and a third generation cephalosporin Children and adults: a third generation cephalosporin Adults over age 50 years: ampicillin and a third generation cephalosporin
History of beta-lactam anaphylaxis: chloramphenicol and vancomycin (plus co-trimoxazole if Listeria is thought possible)
practice because meningeal inflammation disrupts the barrier and allows sufficient penetration. It should be active within purulent and acidic CSF and the rate at which it is metabolised and cleared from CSF determines the frequency and dose that should be given. The choice of antibiotic will be modified by knowledge of local drug resistance patterns for pneumococci and H. influenzae (penicillin-resistant meningococci do not pose a therapeutic problem).80 Antibiotics should be given intravenously in high doses. They should not be given intrathecally. It is prudent to discuss the treatment of any but the most straightforward case of meningitis with a microbiologist or a specialist in infectious diseases.
In cases where an organism cannot be identified, children or adults with presumed bacterial meningitis should be treated with a third generation cephalosporin (cefotaxime or ceftriaxone).88 If cephalosporin-resistant pneumococci are common in the part of world the patient comes from (e.g. Spain or parts of the USA),101-105 then vancomycin or rifampicin should be added. Patients over 50 years and those with defective cell mediated immunity should have ampicillin added (to cover Listeria infection). If there is a clear history of anaphylactic allergy to beta-lactam antibiotics then chloramphenicol and vancomycin should be used (with co-trimoxazole added for the over-50s).88 For empirical treatment of the neutropenic patient, meropenem and an aminoglycoside (to cover possible Pseudomonas infection) are suggested.
Treatment may be modified once pathogens have been identified. For H. influenzae type b infections, ampicillin and chloramphenicol are no longer suitable for empirical treatment, owing to widespread antibiotic resistance. The third generation cephalosporins, cefotaxime or ceftriaxone, have been demonstrated to be effective and are the drugs of choice.80 For meningococcal meningitis, IV benzylpenicillin remains the preferred drug. There have been reports of meningococci resistant to penicillin,106 but this is not associated with clinical failure if the high doses of penicillin used for meningitis are given. Chloramphenicol or a third generation cephalosporin may be used in people who react adversely to penicillin.
Pneumococcal meningitis caused by fully sensitive organisms can be treated with penicillin but penicillin resistant strains are common and a third generation cephalosporin is now the best choice empirical therapy. Once the sensitivity of the pneumococcus to penicillin is confirmed, benzylpenicillin can be chosen. If the pneumococcus is shown to be penicillin resistant but cephalosporin sensitive then the vancomycin and/or rifampicin can be discontinued.
Third generation cephalosporins and meropenem have been shown to be more effective than aminoglycosides for the treatment of gram negative bacillary meningitis and should now be used.107,108 Group B streptococcal infection should be treated with penicillin or ampicillin. Listerial infection responds to ampicillin and for those with penicillin allergy, co-trimoxazole is effective. Flucloxacillin or oxacillin in high doses is recommended for Staphylococcus aureus meningitis, with vancomycin for those who cannot have penicillin or if the organism is methicillin resistant (MRSA).
Shunt infections are commonly caused by coagulase negative staphylococci, and vancomycin, perhaps with added rifampicin, is effective. In most cases it is necessary to remove the device to eradicate the infection completely.109 The combination of penicillin with metronidazole is recommended for anaerobic infections.
The length of time for which treatment is given should be tailored to each case: meningococcal meningitis needs five days of parenteral therapy, H. influenzae 7-10 days, and other forms a minimum of 14 days. Failure to respond adequately prompts a review of the diagnosis and treatment, search for a continuing source of infection, and repeat brain imaging to demonstrate abscess or subdural fluid accumulation. Repeat CSF examination should be considered in cases where the patient is not responding satisfactorily and no explanation can be found.
As mentioned earlier, the release of bacterial cell wall products into the CSF stimulates inflammation, mediated in part by cytokines. Studies to determine the efficacy of the anti-inflammatory action of corticosteroids in reducing this inflammation have produced encouraging results. There is evidence in children that dexamethasone in a dose of 015 mg/kg body weight every six hours for four days reduces the incidence of neurological sequelae,110,111 and this should be given just before antibiotics are started. There is now evidence that a similar approach (dexamethasone 10 mg given just before or with the first dose of antibiotics and continued every six hours for four days) improves the outcome in most adults with acute bacterial meningitis, particularly that caused by pneumococci.112 There is some concern that dexamethasone might reduce the penetration of vancomycin into the CSF and hence there is still some doubt about the routine use of dexamethasone in cases where there is suspicion of meningitis caused by pneumococci that are highly resistant to penicillin or cephalosporin.113
Several other anti-inflammatory agents which act at different stages have been tried but are unhelpful, including non-steroidal anti-inflammatory drugs, pentoxifylline, naloxone, and monoclonal antibodies targeted specifically against human p-integrin.114 Encouraging results have been obtained in meningococcal sepsis with recombinant bactericidal/ permeability increasing protein115 and recombinant activated protein C.116'117
Adjunctive management of bacterial meningitis includes measures to lower any raised intracranial pressure, appropriate intensive care support of cardiorespiratory, coagulation, and renal problems, and maintenance of electrolyte balance.88 Details of these measures are beyond the scope of this account.
In the United Kingdom all cases of bacterial meningitis need to be reported to the Public Health Authorities who are charged with the responsibility for ensuring appropriate steps are taken to minimise the risk of secondary cases (particularly of meningococcal disease). These measures include the use of prophylactic antibiotics and, if necessary, vaccination.118
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