Treatment of Bacterial Infections of the Central Nervous System

  • Gary D. Overturf


Infection of the central nervous system (CNS) represents a medical emergency. Accurate bacteriologic diagnosis is imperative so that specific antimicrobial therapy can be administered. Reduction of mortality is directly related to the specificity of treatment, and many aspects of morbidity may also depend upon the timely employment of specific antibiotics. The CNS represents a special case in practical pharmacology since drug must be delivered to a sequestered anatomic site in bactericidal concentrations at the earliest possible time after administration.


Penicillin Staphylococcus Metronidazole Palmitate Inulin 


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  1. 1.
    Overturf GD, Wehrle PF: Management of bacterial meningitis. In Kagan BM (ed): Antimicrobial therapy, 3rd ed. WB Saunders Co, Philadelphia, pp 286–296, 1980.Google Scholar
  2. 2.
    Geisler PJ, Nelson KE, Levin S, Reddi KT, Moses VK: Community-acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954–1976. Rev Infect Dis 2: 725–745, 1980.CrossRefGoogle Scholar
  3. 3.
    De Louvois J: The bacteriology and chemotherapy of brain abscess. J Antimicrob Chemother 4: 395–413, 1978.PubMedCrossRefGoogle Scholar
  4. 4.
    De Louvois J, Gortavi P, Hurley R: Bacteriology of abscesses of the central nervous system: a multicentre prospective study. Br Med J ii: 985–987, 1977.Google Scholar
  5. 5.
    Dagi TF, Ojemann RG, Zervas NT: Incidence and prevention of infection after neurosurgical operations. In Thompson RA, Green JR (eds): Infectious diseases of the central nervous system. Spectrum Publications Inc, pp 155–173, 1984.Google Scholar
  6. 6.
    Wright RL: A survey of possible etiologic agents in postoperative craniotomy infections. J Neurosurg 25: 125–132, 1966.PubMedCrossRefGoogle Scholar
  7. 7.
    Zia M, Haggerty RJ: Neonatal meningitis. New Engl J Med 259: 314–319, 1978.CrossRefGoogle Scholar
  8. 8.
    Baker CJ: Group B streptococcal infections in neonates. Ped Rev 1: 5–15, 1979.CrossRefGoogle Scholar
  9. 9.
    Desgnez P, Traverse PM: Transport function of plasma proteins. Elsevier, Amsterdam, 1966.Google Scholar
  10. 10.
    Sande MA: Factors influencing the penetration and activity of antibiotics in experimental meningitis. J Infect 3 (Suppl l): 33–38, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Ruedy J: The concentration of penicillins in the cerebrospinal fluid and brain of rabbits with experi-mental meningitis. Can J Physiol Pharmacol 43: 763–772, 1965.CrossRefGoogle Scholar
  12. 12.
    Kunin CM: Effect of protein binding on the distribu-tion of penicillin in the rabbit. J Lab Clin Med 65: 406–412, 1965.PubMedGoogle Scholar
  13. 13.
    Barza M, Brown RB, Shanks C, Gamble C, Weinstein L: Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline, and Oxytetracycline in dogs. Antimicrob Agents Chemother 6: 713–720, 1975.Google Scholar
  14. 14.
    Norrby R: A review of the penetration of antibiotics into CSF and its clinical significance. Scand J Infect Dis 14 (Suppl): 296–309, 1978.Google Scholar
  15. 15.
    Rail DP, Stabnau JR, Zubrod CG: Distribution of drugs between blood and cerebrospinal fluid: general methodology and effect of pH gradients. J Pharmacol Exper Ther 125: 185–193, 1959.Google Scholar
  16. 16.
    Tripathi RC: The functional morphology of the out-flow systems of ocular and cerebrospinal fluid. In Bito LZ, Davison H, Fenstermacher JD (eds): The ocular and cerebrospinal fluids. Academic Press, New York, pp 65–116, 1977.Google Scholar
  17. 17.
    Spector R, Lorenzo AV: Inhibition of penicillin transport from cerebrospinal fluid after intracister- nal inoculation of bacteria. J Clin Invest 54:316— 323, 1974.CrossRefGoogle Scholar
  18. 18.
    Fishman RA, Sligar K, Hake RB: Effect of leukocytes on brain metabolism in granulocytic brain edema. Ann Neurol 2: 89–94, 1977.CrossRefGoogle Scholar
  19. 19.
    Fishman RA: Blood-brain and CSF barriers to penicillin and related organic acids. Arch Neurol 15: 113–124, 1966.PubMedGoogle Scholar
  20. 20.
    Spector R, Lorenzo AV: The effect of salicylate and probenecid on the cerebrospinal fluid transport of penicillin, aminosalicylic acid, and iodide. J Pharmacol Exper Therapeut 188: 55–65, 1974.Google Scholar
  21. 21.
    Kelly RS: Studies of the absorption and distribution of chloramphenicol. Pediatrics 8: 362–367, 1951.PubMedGoogle Scholar
  22. 22.
    Roy TE, Krieger E, Craig G, Cohen D, McNaughton G, Silverthorne N: Studies on the absorption of chloramphenicol in normal children in relation to the treatment of meningitis. Antibiot Chemother 11: 505–516, 1952.Google Scholar
  23. 23.
    Friedman CA, Lovejoy FC, Smith AL: Chloramphenicol distribution in infants and children. J Ped 95:1071–1078, 1979.CrossRefGoogle Scholar
  24. 24.
    Pickering LJ, Hoecker JL, Kramer WG, Kohl S, Cleary TG: Clinical pharmacology of two chloram-phenicol preparations in children: sodium succinate (IV) and palmitate (oral) esters. J Ped 96: 757–765, 1980.CrossRefGoogle Scholar
  25. 25.
    Tuomanen E, Powell K, Marks MI, Laferriere CI, Altmiller DH, Sack C, Smith AL: Oral chloramphenicol in the treatment of H. influenzae meningitis. J Ped 99: 968–974, 1980.CrossRefGoogle Scholar
  26. 26.
    Thrupp LD, Leedom JM, Ivler D, Wehrle PF, Portnoy B, Wehrle PF: Ampicillin levels in the cerebro-spinal fluid during treatment of bacterial meningitis. Antimicrob Agents Chemother 1965: 206–213, 1966.Google Scholar
  27. 27.
    Wilson HD, Haitiin KC: Ampicillin in Haemophilus influenzae meningitis. Am J Dis Child 129: 208–215, 1975.PubMedGoogle Scholar
  28. 28.
    Overturf GD, Steinberg EA, Underman AE, Wilkins J, Leedom JM, Mathies AW, Wehrle PF: Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis. Antimicrob Agents Chemother 11: 420–426, 1975.Google Scholar
  29. 29.
    Greene GR, Overturf GD, Wehrle PF: Ampicillin dosage in bacterial meningitis with special reference to Haemophilus influenzae. Antimicrob Agents Chemother 16: 198–202, 1979.PubMedGoogle Scholar
  30. 30.
    Ivler D, Thrupp LD, Leedom JM, Wehrle PF, Portnoy B: Ampicillin in the treatment of acute bacterial meningitis. Antimicrob Agents Chemother 1963: 335–345, 1964.Google Scholar
  31. 31.
    Thrupp LD, Leedom JM, Ivler D, Wehrle PF, Brown JF, Mathies AW, Portnoy B: Haemophilus influenzae meningitis: a controlled study of treatment with ampicillin. Proceedings of a Conference at the Apothecaries’ Hall, London, June 1964.Google Scholar
  32. 32.
    Fleming PC, Murray JDM, Fujiwara MW, Prichard JS, McNaughton GA: Ampicillin in the treatment of bacterial meningitis. Antimicrob Agents Chemother 1966: 47–52, 1967.Google Scholar
  33. 33.
    Fisher LS, Chow A, Yoshikawa J, Guze LB: Cephalothin and cephaloridine therapy for bacterial meningitis. Ann Intern Med 82: 689–693, 1975.PubMedGoogle Scholar
  34. 34.
    Strausbaugh LJ, Mandaleris CE, Sande MA: Cefamandole and ampicillin in experimental Haemophilus influenzae meningitis. J Infect Dis 135: 210–216, 1977.PubMedCrossRefGoogle Scholar
  35. 35.
    Steinberg EA, Overturf GD, Baraff LJ, Wilkins J: Penetration of cefamandole into spinal fluid. Anti-microb Agents Chemother 11:933–935, 1977.Google Scholar
  36. 36.
    Steinberg EA, Overturf GD, Wilkins J, Baraff LJ, Streng JM, Leedom JM: Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b. J Infect Dis 137: S180–186, 1978.PubMedCrossRefGoogle Scholar
  37. 37.
    Galvao PAA, Lomar AV, Francisco W, de Godoy CVF, Norrby R: Cefoxitin penetration into cerebrospinal fluid in patients with purulent meningitis. Antimicrob Agents Chemother 17: 526–529, 1980.PubMedGoogle Scholar
  38. 38.
    Feldman WE, Moffit S, Manning NS: Penetration of cefoxitin into cerebrospinal fluid of infants and children with bacterial meningitis. Antimicrob Agents Chemother 21: 468–471, 1982.PubMedGoogle Scholar
  39. 39.
    Report from a Swedish Study Group, R. Norrby, Coordinator: Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis. Lancet 1: 295–298, 1982.Google Scholar
  40. 40.
    Landesman SH, Corrado ML, Cherubin CC, Cleri D: Diffusion of a new beta-lactam (LY 127935) into cerebrospinal fluid. Implications for therapy of gram-negative meningitis. Am J Med 69: 92–98.Google Scholar
  41. 41.
    Kaplan SH, Mason EO, Garcia H, Kvernland SJ, Loiselle EM, Anderson DC, Mintz A A, Feigin RD: Pharmacokinetics and cerebrospinal fluid penetration of moxalactam in children with bacterial meningitis. J Ped 98: 152–157, 1981.CrossRefGoogle Scholar
  42. 42.
    Chartrand SA, Marks MI, Scribner RK, Johnston JT, Frederick DF: Moxalactam therapy of Haemophilus influenzae meningitis in children. J Ped 104: 454–458, 1984.CrossRefGoogle Scholar
  43. 43.
    Rajal JJ, Simberkoff MS, Landesman SH, Metro-politan Meningitis Study Group: Prospective evalu ation of moxalactam therapy for gram-negative bacillary meningitis. J Infect Dis 149: 562–567, 1984.CrossRefGoogle Scholar
  44. 44.
    Kayser FH, Huf E, Homberger F: The microbiology of cefoperazone. Infection 9 (Suppl): S6–10, 1981.CrossRefGoogle Scholar
  45. 45.
    Cable D, Overturf GD, Edrajin G: Concentrations of cefoperazone in cerebrospinal fluid during bacterial meningitis. Antimicrob Agents Chemother 23: 688–691, 1983.PubMedGoogle Scholar
  46. 46.
    Cherubin CC, Corrado ML, Nair SR, Gombert ME, Landesman S, Humbert G: Treatment of gram-negative bacillary meningitis: role of the new cephalosporin antibiotics. Rev Infect Dis 4 (Suppl): S453–464, 1982.PubMedCrossRefGoogle Scholar
  47. 47.
    Belohradsky BH, Bruch K, Geiss D, Kafetzis D, Marget W, Peters G: Intravenous cefotaxime in children with bacterial meningitis. Lancet 1: 61–63, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Kobayashi Y, Morikawa Y, Haruta T: Clinical evaluation of cefotaxime in the treatment of purulent meningitis in children. Clin Ther 4 (Suppl A): 89–110, 1981.PubMedGoogle Scholar
  49. 49.
    Barry AL, Jones RN, Thornsberry C, Fuchs PC, Gerlach EH, Sommers HM: Ceftizoxime: collaborative mutiphased invitro evaluation including tentative interpretive standards for disc susceptibility tests, beta-lactamase stability and inhibition. J Antimicrob Chemother 10 (Suppl C): 25–4, 1982.PubMedGoogle Scholar
  50. 50.
    Overturf GD, Cable DC, Forthal DN, Shikuma C: Treatment of bacterial meningitis with ceftizoxime. Antimicrob Agents Chemother 25: 258–262, 1984.PubMedGoogle Scholar
  51. 51.
    Neu H, Meropol NJ, Fu KP: Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase stable cephalosporin. Antimicrob Agents Chemother 19: 414–423, 1981.PubMedGoogle Scholar
  52. 52.
    Sakata Y, McCracken GH, Thomas ML, Olsen KD: Pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone in experimental meningitis due to an ampicillin and chlorampheni- col-resistant strain of Haemophilus influenzae type b. Antimicrob Agents Chemother 25: 29–32, 1984.PubMedGoogle Scholar
  53. 53.
    Congeni BL: Comparison of ceftriaxone and traditional therapy of bacterial meningitis. Antimicrob Agents Chemother 25: 40–44, 1984.PubMedGoogle Scholar
  54. 54.
    Martin E, Koup JR, Paravicini U, Stoeckel K: Pharmacokinetics of ceftriaxone in neonates and infants with meningitis. J Ped 105: 475–481, 1984.CrossRefGoogle Scholar
  55. 55.
    Hatch D, Forthal D, Leong G, Overturf G: Treatment of bacterial meningitis in children with ceftazidime. 8th Annual Meeting of American Society for Microbiology, abstract 97A, 1985.Google Scholar
  56. 56.
    Rodriquez WJ, Puig JR, Kahn WN, Feris J, Gold B, Sturla C: Ceftazidime versus ampicillin and chloramphenicol in meningitis. Abstracts of the 23rd Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract 237, 1984.Google Scholar
  57. 57.
    Scheid WM: Rationale for optimal dosing of betalactam antibiotics in therapy for bacterial meningitis. Eur J Clin Microbiol 3: 579–591, 1984.CrossRefGoogle Scholar
  58. 58.
    Schoenbaum SC: Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations and therapy. J Infect Dis 13: 543–552, 1975.CrossRefGoogle Scholar
  59. 59.
    Noel GJ, Edelson PJ: Staphylococcus epidermidis bacteremia in neonates: further observations and the occurrence of focal infection. Pediatrics 74: 832–837, 1984.PubMedGoogle Scholar
  60. 60.
    Kane JG, Parker RH, Jordan GW, Hoeprich PD: Nafcillin concentration in cerebrospinal fluid during treatment of staphylococcal infections. Ann Intern Med 87: 309–11, 1977.PubMedGoogle Scholar
  61. 61.
    Oppenheimer S, Beaty HN, Petersdorf RG: Pathogenesis of meningitis. VIII. Cerebrospinal fluid and blood concentrations of methicillin, cephalothin and cephaloridine in experimental pneumococcal meningitis. J Lab Clin Med 73: 535–543, 1969.PubMedGoogle Scholar
  62. 62.
    Morikawa Y, Haruta T, Kobayashi Y: Half-lives of penicillins and cephalasporins in the cerebrospinal fluid of rabbits with staphylococcal meningitis. In Nelson JD, Grassi C (eds): Current chemotherapy and infectious diseases. Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, vol. 1. American Society of Microbiology, Washington, DC, pp 640–641, 1980.Google Scholar
  63. 63.
    Strausbaugh LJ, Murrary TW, Sande MA: Compar-ative penetration of six antibiotics into the cerebro-spinal fluid of rabbits with experimental staphylococcal meningitis. J Antimicrob Chemother 6: 363–371, 1980.PubMedCrossRefGoogle Scholar
  64. 64.
    Gump D: Vancomycin for the treatment of bacterial meningitis. Rev Infect Dis 3 (Suppl): S289–292, 1981.PubMedGoogle Scholar
  65. 65.
    Redfield D, Underman A, Norman D, Overturf GD: Cerebrospinal fluid penetration of vancomycin in bacterial meningitis. In Nelson JD, Grassi C (eds): Current chemotherapy and infectious disease. Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference an Antimicrobial Agents and Chemotherapy, vol. 1. American Society for Microbiology, Washington, DC, pp 638–640, 1980.Google Scholar
  66. 66.
    Schaad UB, McCracken GH, Nelson JD: Clinical pharmacology and efficacy of vancomycin in pediatric patients. J Ped 96: 119–126, 1980.CrossRefGoogle Scholar
  67. 67.
    Congeni BL, Tan J, Salstrom SJ, Weinstein L: Kinetics of vancomycin after intraventricular and intravenous administration. Soc Ped Res, abstract 799, 1980.Google Scholar
  68. 68.
    Lerner PI: Penetration of cephalothin and lincomy- cin into the cerebrospinal fluid. Am J Med Sei 257: 125–131, 1969.CrossRefGoogle Scholar
  69. 69.
    McCracken G: Rate of bacteriologic response to antimicrobial therapy in neonatal meningitis. Am J Dis Child 123: 547–553, 1972.PubMedGoogle Scholar
  70. 70.
    McCracken GH, Mize S: A controlled study of intrathecal antibiotic therapy in gram-negative meningitis of infancy. J Ped 89: 66–72, 1976.CrossRefGoogle Scholar
  71. 71.
    McCracken GH, Mize S, Threlkeld N: Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Lancet, April 12: 787–791, 1980.Google Scholar
  72. 72.
    Rahal JJ, Hyams PJ, Simberkoff MS, Rubinstein MS: Combined intrathecal and intramuscular gentamicin for gram-negative meningitis. New Engl J Med 200: 1394–1398, 1974.CrossRefGoogle Scholar
  73. 73.
    Kaiser AB, McGee ZA: Aminoglycoside therapy of gram-negative bacillary meningitis. New Engl J Med 293: 1215–1220, 1975.PubMedCrossRefGoogle Scholar
  74. 74.
    Strausbaugh LJ, Mandaleris CD, Sande MA: Com-parison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis. J Lab Clin Med 89: 692–701, 1977.Google Scholar
  75. 75.
    Spector R: The transport of gentamicin in the choroid plexus and CSF. J Pharmacol Exper Ther 194: 82–88, 1975.Google Scholar
  76. 76.
    Schauf V, Deveikis A, Riff L, Serota A: Antibiotic killing kinetics of group B streptococci. J Ped 89: 194–198, 1976.CrossRefGoogle Scholar
  77. 77.
    Overturf GD, Horowitz M, Wilkins J, Leedom J, Steinberg EA: Bactericidal studies of penicillin-gen- tamicin combinations against group B streptococci. J Antibiot 30: 513–518, 1977.PubMedGoogle Scholar
  78. 78.
    Deveikis A, Scharf V, Mizen M, Riff L: Antimicrobial therapy of experimental group B streptococcal infections in mice. Antimicrob Agents Chemother 1: 817–820, 1977.Google Scholar
  79. 79.
    Scheid WM, Fletcher DD, Fink FN, Sande MA: Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. J Infect Dis 140: 287–294, 1979.CrossRefGoogle Scholar
  80. 80.
    Lepper MH, Dowling HF: Treatment of pneumo- coccic meningitis with penicillin compared with penicillin plus aureomycin. Studies including observations of an apparent antagonism between penicillin and aureomycin. Arch Intern Med 88: 489–494, 1951.Google Scholar
  81. 81.
    Mathies AW, Leedom JM, Ivler D, Wehrle PF, Portnoy B: Antibiotic antagonism in bacterial meningitis. Antimicrob Agents Chemother 1967: 218–224, 1966.Google Scholar
  82. 82.
    Kirwan WO: Cerebrospinal fluid cotrimoxazole levels. J Isr Med Assoc 67: 76–81, 1974.Google Scholar
  83. 83.
    LaFaix CH: Une nouvelle chimicotherapie anti-in- fectieuse majeure: l’association sulfamethoxazolep rime. LaPresse Med 78: 1375–1377, 1970.Google Scholar
  84. 84.
    Sabel KG, Brandenburg A: Treatment of meningitis and septicemia in infancy with sulfamethoxazole/ trimethoprim combination. Acta Ped Scand 64: 25–32, 1975.CrossRefGoogle Scholar
  85. 85.
    Ingham HR, Selkon JB, Roxby CM: The bacteriol-ogy and chemotherapy of otogenic cerebral abscesses. J Antimicrob Chemother 4 (Suppl C): 63–69, 1978.PubMedGoogle Scholar
  86. 86.
    Kramer PW, Griffith RS, Campbell RL: Antibiotic penetration of the brain. A comparative study. J Neurosurg 31: 295–302, 1969.PubMedCrossRefGoogle Scholar
  87. 87.
    Wellman WR, Dodge HW, Heilman FR, Petersen MC: Concentration of antibiotics in the brain. J Lab Clin Med 43: 275–279, 1974.Google Scholar
  88. 88.
    Black P, Graybill R, Charache P: Penetration of brain abscess by systemically administered antibiotics. J Neurosurg 38: 705–709, 1973.PubMedCrossRefGoogle Scholar

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  • Gary D. Overturf

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