title: Bacterial meningitis. Rational selection and use of antibacterial drugs.
abstract: Bacterial meningitis is a continuing challenge. This applies especially to infections in the neonate and the elderly, and to those which are hospital acquired. Factors which maintain the high morbidity and significant mortality from this disease include microbial virulence, a limited host response to infection within the cerebrospinal fluid (CSF), where phagocyte function is often impaired and complement and opsonic antibody activity are deficient, as well as delays in diagnosis and treatment. Added to these adverse factors is the pharmacokinetic hurdle of the 'blood-brain barrier', which limits drug concentrations achievable within the CSF. Inflammatory changes certainly improve the penetration of many agents, especially the penicillins and cephalosporins, but it must be remembered that with resolution of inflammation, achievable concentrations decline. Hence, the necessity for continuing parenteral administration of antibiotics throughout the treatment period. Although penicillin G (benzylpenicillin) remains the drug of choice for both pneumococcal and meningococcal infections, increasing resistance to ampicillin among Haemophilus influenzae has lead to greater reliance on alternative agents. Chloramphenicol is widely used, yet is potentially toxic, so that therapy with cefuroxime and the newer cephalosporins has been increasingly advocated. The advent of these potent, broad spectrum cephalosporins has induced a reappraisal of the treatment of Gram-negative bacillary meningitis, where ampicillin resistance and poor CSF penetration by the aminoglycosides have contributed to an unsatisfactory impact on outcome. Agents such as cefotaxime and ceftazidime have proved effective, although greater controlled experience is required. Finally, the contagious nature of meningococcal and H. influenzae infections justifies offering chemoprophylaxis to selected contacts, with rifampicin (or minocycline for contacts of patients with meningococcal infections).
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D002511:Cephalosporins / Q000627:therapeutic use; D002701:Chloramphenicol / Q000627:therapeutic use; D004338:Drug Combinations / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007700:Kinetics; D008581:Meningitis / Q000188:drug therapy* / Q000209:etiology; D010406:Penicillins / Q000627:therapeutic use; D013420:Sulfamethoxazole / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D014295:Trimethoprim / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D004338:Drug Combinations; D010406:Penicillins; D013449:Sulfonamides; D002701:Chloramphenicol; D014640:Vancomycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole