Central Nervous System Infections

CENTRAL NERVOUS SYSTEM INFECTIONS

The brain, its surrounding covering of meninges and the spinal cord are subject to infection, which is generally blood-borne but may also complicate neurosurgery, penetrating injuries or direct spread from infection in the middle ear or nasal sinuses. Viral meningitis is the most common infection but is generally self-limiting. Occasionally destructive forms of encephalitis occur; an example is herpes simplex encephalitis. Bacterial infections include meningitis and brain abscesses and carry a high risk of mortality, while in those who recover, residual neurological damage or impairment of intellectual function may follow. This occurs despite the availability of antibiotics active against the responsible bacterial pathogens. Fungal infections of the brain, although rare, are increasing in frequency, particularly among immunocompromised patients who either have underlying malignant conditions or are on potent cytotoxic drugs.

The treatment of bacterial infections of the central nervous system highlights a number of important therapeutic considerations. Bacterial meningitis is caused by a variety of bacteria although their incidence varies with age. In the neonate, E. coli and group B streptococci account for the majority of infections, while in the preschool child H. influenzae was the commonest pathogen before the introduction of a highly effective vaccine. Neisseria meningitidis has a peak incidence between 5 and 15 years of age, while pneumococcal meningitis is predominantly a disease of adults.

Ceftriaxone is the drug of choice for the treatment of group B streptococcal, meningococcal and pneumococcal infections but, as discussed earlier, CSF concentrations of penicillin are significantly influenced by the intensity of the inflammatory response. To achieve therapeutic concentrations within the CSF, high dosages are required, and in the case of pneumococcal meningitis should be continued for 10–14 days. Resistance among Strep. pneumoniae to penicillin has increased worldwide; in travellers returning from endemic areas, vancomycin may be indicated. Alternative agents include meropenem.

Resistance of H. influenzae to ampicillin has increased in the past two decades and varies geographically. Thus, it can no longer be prescribed with confidence as initial therapy, and cefotaxime or ceftriaxone are now the preferred alternatives. However, once laboratory evidence for β-lactamase activity is excluded, ampicillin can be safely substituted.

E. coli meningitis carries a mortality of greater than 40% and reflects both the virulence of this organism and the pharmacokinetic problems of achieving adequate CSF antibiotic levels. The broad-spectrum cephalosporins such as cefotaxime, ceftriaxone or ceftazidime have been shown to achieve satisfactory therapeutic levels and are the agents of choice to treat Gram-negative bacillary meningitis. Treatment again must be prolonged for periods ranging from 2 to 4 weeks.

Brain abscess presents a different therapeutic challenge. An abscess is locally destructive to the brain and causes further damage by increasing intracranial pressure. The infecting organisms are varied but those arising from middle ear or nasal sinus infection are often polymicrobial and include anaerobic bacteria, microaerophilic species and Gram-negative enteric bacilli. Less commonly, a pure Staph. aureus abscess may complicate blood-borne spread. Brain abscess is a neurosurgical emergency and requires drainage. However, antibiotics are an important adjunct to treatment. The polymicrobial nature of many infections demands prompt and careful laboratory examination to determine optimum therapy. Drugs are selected not only on their ability to penetrate the blood–brain barrier and enter the CSF but also on their ability to penetrate the brain substance. Metronidazole has proved a valuable alternative agent in such infections, although it is not active against microaerophilic streptococci, which must be treated with high-dose benzylpenicillin. The two are often used in combination. Chloramphenicol is an alternative agent.