Summary
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).
Similar content being viewed by others
References
Aranoff SC, Reed MD, O’Brien CA, Blumer JL. Comparison of the efficacy and safety of ceftriaxone to ampicillin chloram-phenicol in the treatment of childhood meningitis. Journal of Antimicrobial Chemotherapy 13: 143–151, 1984
Barza M, Weinstein L. Pharmacokinetics of the penicillins in man. Clinical Pharmacokinetics 1: 297–308, 1976
Beam TR, Allen JC. Blood, brain and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges. Antimicrobial Agents and Chemotherapy 12: 710–716, 1977
Belohradsky BH, Bruck K, Geiss D, Kafetzis D, Margaret W, et al. Intravenous cefotaxime in children with bacterial meningitis. Lancet 1: 61–63, 1980
Bloom C. Personal communication, 1985
Cable D, Edralin G, Overturf GD. Human cerebrospinal fluid pharmacokinetics and treatment of bacterial meningitis with ceftizoxime. Journal of Antimicrobial Chemotherapy 10 (Suppl.): 121–128, 1982
Carrizosa J, Kobasa WD, Kaye D. Antagonism between chloramphenicol and penicillin in streptococcal endocarditis in rabbits. Journal of Laboratory and Clinical Medicine 85: 307–311, 1975
Cherubin CE, Marr JS, Sierra MF, Becker S. Listeria and gram negative bacillary meningitis in New York City, 1972–79. American Journal of Medicine 71: 199–209, 1981
Cole FS, Daum RS, Teller L, Goldman DA, Smith A. Effect of ampicillin and chloramphenicol alone and in combination on ampicillin-susceptible and -resistant Haemophilus influenzae type b. Antimicrobial Agents and Chemotherapy 15: 415–419, 1979
Congeni BL. Comparison of ceftriaxone and traditional therapy of bacterial meningitis. Antimicrobial Agents and Chemotherapy 25: 40–44, 1984
Davson H, Smith HV. Discussion on penetration of drugs into the cerebrospinal fluid. Proceedings of the Royal Society of Medicine 50: 963–966, 1957
DeLos A, DelRio M, Shelton M, Chrone D, McCraken Jr GH, et al. Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. Lancet 1: 1241–1244, 1983
Durack DT, Sponos A. End of treatment spinal tap in bacterial meningitis. Is it worthwhile? Journal of the American Medical Association 248: 75–78, 1982
Fong IW. Tomlins B. Penetration of ceftazidime into CSF of patients with and without evidence of meningeal inflammation. Antimicrobial Agents and Chemotherapy 26: 15–116, 1984
Fossieck B, Parker RH. Neurotoxicity during intravenous infusion of penicillin: a review. Journal of Clinical Pharmacology 14: 504–512, 1974
Hawley HB, Gump DW. Vancomycin therapy in bacterial meningitis. American Journal of Diseases of Children 126: 261–266, 1973
Hodges GR, Perkins RL. Acute bacterial meningitis: an analysis of factors influencing prognosis. American Journal of Medical Science 270: 427–440, 1975
Kafetzis DA. Brater DC, Kapiki AN, Papas CV, Dellagrammaticas H, et al. Treatment of severe neonatal infection with cefotaxime: efficacy and pharmacokinetics. Journal of Paediatrics 100: 483–489, 1982
Kaiser AB. McGee ZA. Aminoglycoside therapy in gram negative bacillary meningitis. New England Journal of Medicine 293: 1215. 1975
King SD. Ramfal A, Wynter H, Moodie K, Castle D, et al. Safety and immunogenicity of a new Haemophilus influenzae tybe b vaccine in infants under one year of age. Lancet 2: 705–709, 1981
Kramer PW, Griffith RS, Campbell RL. Antibiotic penetration of the brain: a comparative study. Journal of Neurosurgery 31: 295–302, 1969
Lambert HP. Prophylaxis in Haemophilus meningitis. British Medical Journal 288: 739–740, 1984
Landesman SH, Corrado ML, Shah PM, Armengauld M, Barza M, et al. Past and current roles for cephalosporin antibiotics in treatment of meningitis. American Journal of Medicine 71: 693–703, 1981
Lecour H, Seara A, Miranda M, Cordeiro J, Sarmento J. Treatment of 160 cases of acute bacterial meningitis with cefotaxime. Journal of Antimicrobial Chemotherapy 14 (Suppl. B): 195–202, 1984
Lepow ML, Gold R. Meningococcal A and other polysacohoride vaccines. A five year progress report. New England Journal of Medicine 308: 1158–1160, 1983
Lepper MH, Dowling HF. Treatment of pneumococci meningitis with penicillin compared with penicillin plus aureomycin. Studies including an apparent antagonism between penicillin and aureomycin. Archives of Internal Medicine 88: 489–494, 1951
Levitz RE, Quintilani R. Trimethoprim-sulfamethoxazole for bacterial meningitis. Annals of Internal Medicine 100: 881–890, 1984
Lithander A. Benzylpenicillin and ampicillin in the cerebrospinal fluid during experimental Haemophilus influenzae meningitis. Antimicrobial Agents and Chemotherapy, pp. 435–438, 1966
McCabe WR. Empiric therapy for bacterial meningitis. Review of Infectious Diseases 5: 574–583, 1983
McCracken Jr GH, Mize SG. A controlled study of intrathecal antibiotic therapy in gram negative enteric meningitis in infancy. Journal of Paediatrics 89: 66–72, 1976
McCracken Jr GH, Mize SG, Threlkeld N. Intraventricular gentamicin therapy in gram negative meningitis in infancy. Lancet 1: 787–791, 1980
McCracken Jr GH, Threlkeld N, Mize SG. Moxalactam therapy for neonatal meningitis due to gram negative enteric bacilli. A prospective controlled evaluation. Journal of the American Medical Association 252: 1427–1432, 1984
Mulhall A, de Louvois J, Hurley R. Chloramphenicol toxicity in neonates: its incidence and prevention. British Medical Journal 287: 1424–1427, 1983a
Mulhall A, de Louvois J, Hurley R. Efficacy of chloramphenicol in the treatment of neonatal and infantile meningitis: a study of 70 cases. Lancet 1: 284–287, 1983b
Murphy TV, Chrane DF, McCraken Jr GH, Nelson JD. Rifampicin prophylaxis versus placebo for household contacts of children with Haemophilus influenzae type b disease. American Journal of Diseases in Children 137: 627–632, 1983
Norrby R, and the Swedish Study Group. Cefuroxime versus ampicillin and chloramphenicol for treatment of bacterial meningitis. Lancet 1: 295–298, 1982
Overturf GD, Cable DC, Forthal DN, Shikuma C. Treatment of bacterial meningitis with ceftizoxime. Antimicrobial Agents and Chemotherapy 25: 258–262, 1984
Pehtola H. Meningococcal disease: still with us. Reviews of Infectious Diseases 5: 71–91, 1983
Perfect JR, Lang SDR, Durack DT. Comparison of cotrimoxazole, ampicillin and chloramphenicol in treatment of experimental Haemophilus influenzae type b meningitis. Antimicrobial Agents and Chemotherapy 17: 43–48, 1980
Phillips I. Aminoglycosides. Lancet 2: 311–314, 1982
Schaad UB. Chemoprophylaxis for the prevention of bacterial meningitis. Infection 12 (Suppl.): 1–13, 1984
Scheid WM, Fletcher DD, Fink FN, Sande MA. Response to therapy in the experimental rabbit model of meningitis due to Listeria monocytogenes. Journal of Infectious Diseases 160: 287–296, 1979
Scheid WM, Alliegro GM, Field MR, Brodeur SP. Synergism between ampicillin and gentamicin in experimental meningitis due to Group B streptococci. Journal of Infectious Diseases 146: 100, 1982
Scheid WM, Sande MA. Bactericidal versus bacteriostatic antibiotic therapy of experimental pneumococcal meningitis in rabbits. Journal of Clinical Investigation 71: 411–419, 1983
Scott JL, Finegold SM, Belkin GA, Lawrence JS. A controlled double blind study of the haematologic toxicity of chloramphenicol. New England Journal of Medicine 272: 1137–1142, 1985
Sell SHW, Webb WW, Pete JE, Doyne EO. Physiological sequelae to bacterial meningitis: two controlled studies. Paediatrics 49: 212–217, 1972
Shapino ED. Prophylaxis for contacts of patients with meningococcal or Haemophilus influenzae type b disease. Paediatric Infectious Diseases 1: 132–138, 1982
Simasthien S, Duangmani C, Echeverria P. Haemophilus influenzae type b resistant to ampicillin and chloramphenicol in an orphanage in Thailand. Lancet 2: 1214–1217, 1980
Sirinavin S, Chiemchanya S, Visudhipan P, Lolekha S. Cefuraxime treatment of bacterial meningitis in infants and children. Antimicrobial Agents and Chemotherapy 25: 273–275, 1984
Slaughter RL, Pieper JA, Cerra TB, Brodsky B, Koup JR. Chloramphenicol sodium succinate kinetics in critically ill patients. Clinical Pharmacology and Therapeutics 28: 69–77, 1980
Spagnuolo PJ, Ellner JJ, Lerner PI, McHenry MC, Fiataver F, et al. Haemophilus influenzae meningitis: the spectrum of disease in adults. Medicine (Baltimore) 61: 74–85, 1982
Steele WR. Ceftriaxone therapy in meningitis and serious infections. American Journal of Medicine 77(4C): 50–53, 1984
Strausbough LJ, Mandaleris CD, Sande MA. Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis. Journal of Laboratory and Clinical Medicine 89: 692–701, 1977
Swatz MN. Intraventricular use of aminoglycosides in the treatment of gram negative bacillary meningitis: conflicting views. Journal of Infectious Diseases 143: 293–296, 1981
Tauber MG, Duroshow CA, Hackbath CJ, Rusnak MG, Drake TA, et al. Antibacterial activity of beta-lactam antibiotics in experimental pneumococcal meningitis. Journal of Infectious Diseases 149: 568–574, 1984
Tuomanen E, Powell KR, Marks MI, Laferriere CI, Altmiller DH, et al. Oral chloramphenicol in the treatment of Haemophilus influenzae meningitis. Journal of Paediatrics 99: 968–974, 1981
Uchiyama N, Greene GR, Kilts KB, Thrupp LD. Meningitis due to Haemophilus influenzae type b resistant to ampicillin and chloramphenicol. Journal of Paediatrics 97: 421–424, 1980
Uwaydah M, Tannir N, Kantnrjin H, Osseiran M, Bal AF. Moxalactam therapy of bacterial meningitis in adults. Antimicrobial Agents and Chemotherapy 23: 289–292, 1983
Ward JI, Tsai TF, Filice GA, Fraser DW. Prevalence of ampicillin and chloramphenicol resistant strains of Haemophilus influenzae causing meningitis and bacteremia: national survey of hospital laboratories. Journal of Infectious Diseases 138: 421–424, 1978
Wehrle PF, Mathie AW, Leedom J, Ivler D. Bacterial meningitis. Annals of New York Academy of Science 145: 488–498, 1967
Williams KJ, Fourd RD. Ceftazidime for pseudomonas meningitis. Lancet 1: 464, 1985
Wright PF, Kaiser AB, Bowman CM, McKee KT, Truzillo H, McGee ZA. The pharmacokinetics and efficacy of an aminoglycoside administered into the cerebral ventricles in neonates: implications for further evaluation of this route of therapy in meningitis. Journal of Infectious Diseases 143: 141–147, 1981
Vogev R, Schreiber M, Gardner S, Schulman ST. Moxalactam in the treatment of paediatric infections. American Journal of Diseases in Children 136: 836–839, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Whitby, M., Finch, R. Bacterial Meningitis. Drugs 31, 266–278 (1986). https://doi.org/10.2165/00003495-198631030-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198631030-00004