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Pharmacokinetic Optimisation of the Treatment of Bacterial Central Nervous System Infections

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Abstract

Central nervous system (CNS) infections caused by bacteria with reduced sentivity to antibacterials are an increasing worldwide challenge. In successfully treating these infections the following conditions should be considered: (i) Antibacterials do not distribute homogeneously in the central nervous compartments [cerebrospinal fluid (CSF), extracellular space of the nervous tissue, intracellular space of the neurons, glial cells and leucocytes]. Even within the CSF, after intravenous administration, a ventriculo-lumbar concentration gradient is often observed, (ii) Valid parameters of drug entry into the CSF are the CSF: serum concentration ratio in steady state and the CSF: serum ratio of the area under the concentration-time curves (AUCcsf/AUCs). Frequently, the elimination half-life (t½β) in CSF is longer than t½β in serum, (iii) For most antibacterials, lipophilicity, molecular weight and serum protein binding determine the drug entry into the CSF and brain tissue. With an intact blood-CSF and blood-brain barrier, the entry of hydrophilic antibacterials (β-lactam antibacterials, glycopeptides) into the CNS compartments is poor and increases during meningeal inflammation. More lipophilic compounds [metronidazole, quinolones, rifampicin (rifampin) and chloramphenicol] are less dependent on the function of the blood-CSF and blood-brain barrier (iv) Determiniation of the minimal inhibitory concentrations (MIC) of the causative organsim is necessary for optimisation of treatment. (v) For rapid sterilisation of CSF, drug concentrations of at least 10 times MIC are required. The minimum CSF concentration: MIC ratio ensuring successful therapy is unknown.

Strategies to achieve optimum antibacterial concentrations in the presence of minor distrubances of the blood-CSF and blood-brain barrier include, the increased use of low toxicity antibacterials (e.g., β-lactam antibiotics), the use of moderately lipophilic compounds, and the combination of intravenous and intraventricular administration.

Antibacterials which do not interfer with bacterial cell wall synthesis delay and/or decrease the liberation of proinflammatory bacterial products, delay or inhibit tumour necrosis factor release, and may reduce brain oedema in experimental meningitis. Conclusive evidence of the reduction of neuronal damage by this approach, however, is lacking.

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References

  1. Quagliarello V, Scheid WM. Bacterial meningitis: pathogenesis, pathophysiology and progress. N Engl J Med 1992; 327: 864–72.

    Article  PubMed  CAS  Google Scholar 

  2. Durand ML, Calderwood, SB, Weber DJ, et al. Acute bacterial meningitis in adults: a review of 493 episodes. N Engl J Med 1993; 328, 21–8.

    Article  PubMed  CAS  Google Scholar 

  3. Helwig H. Empfehlungen der Arbeitsgemeinschaft ‘Meningitis der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. zur Diagnostik und Therapie der bakteriellen Meningitis. Z Antimikrob Antineoplast Chemother 1984; 2: 209–13.

    Google Scholar 

  4. Pikis A, Donkersloot JA, Akram S, et al. Decreased susceptibility to imipenem among penicillin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 1997; 40: 105–8.

    Article  PubMed  CAS  Google Scholar 

  5. Crone C. The blood-brain barrier: facts and questions. In: Siesjö BK, Sörensen SC, editors. Ion homeostasis of the brain. Copenhagen: Munksgaard, 1971: 52–62.

    Google Scholar 

  6. Nabeshima S, Reese TS, Landis DMD, et al. Junctions in the meninges and marginal glia. J Comp Neurol 1975; 164: 127–70.

    Article  PubMed  CAS  Google Scholar 

  7. Brightman MW, Reese TS. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 1969; 40: 648–77.

    Article  PubMed  CAS  Google Scholar 

  8. Rosenberg GA, Kyner WT, Estrada E. Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions. Am J Physiol 1980; 238: H42–8.

    Google Scholar 

  9. Nau R, Sörgel F, Prange HW. Lipophilicity at pH 7.4 and molecular size govern the entry of not actively transported drugs into the cerebrospinal fluid in humans with uninflamed meninges. J Neurol Sci 1994; 122: 61–5.

    Article  PubMed  CAS  Google Scholar 

  10. Norrby SR. Role of cephalosporins in the treatment of bacterial meningitis in adults: overview with special emphasis on ceftazidime. Am J Med 1985; 79 Suppl. 2A: 56–61.

    Article  PubMed  CAS  Google Scholar 

  11. Nau R, Prange HW, Muth P, et al. Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. Antimicrob Agents Chemother 1993; 37: 1518–24.

    Article  PubMed  CAS  Google Scholar 

  12. Nau R, Prange HW, Kinzig M, et al. Cerebrospinal fluid ceftazidime kinetics in patients with external ventriculostomies. Antimicrob Agents Chemother 1996; 40: 763–6.

    PubMed  CAS  Google Scholar 

  13. Nau R, Lassek C, Kinzig-Schippers M, et al. Disposition and elimination of meropenem in the cerebrospinal fluid of hydro-cephalic patients with external ventriculostomy [poster A50]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28–Oct 1; Toronto.

    Google Scholar 

  14. Nau R, Kinzig-Schippers M, Sörgel F, et al. Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of hydrocephalic patients. Antimicrob Agents Chemother 1997; 41: 987–91.

    PubMed  CAS  Google Scholar 

  15. Nakagawa H, Yamada M, Tokiyoshi K, et al. Penetration of potassium clavulanate/ticarcillin sodium into cerebrospinal fluid in neurosurgical patients. Jpn J Antibiot 1994; 47: 93–101.

    PubMed  CAS  Google Scholar 

  16. Kühnen E, Pfeifer G, Frenkel C. Penetration of fosfomycin into cerebrospinal fluid across non-inflamed and inflamed meninges. Infection 1987; 15: 422–4.

    Article  PubMed  Google Scholar 

  17. Nau R, Scholz P, Sharifi S, et al. Netilmicin cerebrospinal fluid concentrations after an intravenous infusion of 400mg in patients without meningeal inflammation. J Antimicrob Chemother 1993; 32: 893–6.

    Article  PubMed  CAS  Google Scholar 

  18. Nau R, Prange HW, Menck S, et al. Passage of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges. J Antimicrob Chemother 1992; 29: 719–24.

    Article  PubMed  CAS  Google Scholar 

  19. Dudley MN, Levitz RE, Quintiliani R, et al. Pharmacokinetics of trimethoprim and sulfamethoxazole in serum and cerebrospinal fluid of adult patients with normal meninges. Antimicrob Agents Chemother 1984; 26: 811–4.

    Article  PubMed  CAS  Google Scholar 

  20. Nau R, Prange HW, Martell J, et al. Penetration of ciprofloxacin into the cerebrospinal fluid of patients with uninflamed meninges. J Antimicrob Chemother 1990; 25: 965–73.

    Article  PubMed  CAS  Google Scholar 

  21. Karimi A, Knothe H, Scholl H. Penetration von Ciprofloxacin in den Liquor Vergleich zu Ofloxacin. Fortschr Antimikrob Antineoplast Chemother 1991; 10 (3): 289–97.

    Google Scholar 

  22. Nau R, Kinzig M, Dreyhaupt T, et al. Cerebrospinal fluid kinetics of ofloxacin and its metabolites after a single intravenous infusion of 400mg ofloxacin. Antimicrob Agents Chemother 1994; 38: 1849–53.

    Article  PubMed  CAS  Google Scholar 

  23. Bouquet S, Desbordes JM, Muckensturm M, et al. Pharmacokinetics and cerebrospinal diffusion of ofloxacin after intravenous infusion in hydrocephalic patients. Rev Infect Dis 1989; 11 Suppl. 5: S1207–8.

    Google Scholar 

  24. Dow J, Chazal J, Frydman AM, et al. Transfer kinetics of pefloxacin into cerebro-spinal fluid after one hour iv infusion of 400mg in man. J Antimicrob Chemother 1986; 17 Suppl. B: 81–7.

    Article  PubMed  Google Scholar 

  25. Ebert S, Leggett J, Vogelman B, et al. Evidence for a slow elimination phase for penicillin G. J Infect Dis 1988; 158: 200–2.

    Article  PubMed  CAS  Google Scholar 

  26. Woodnut G, Berry V, Mizen L. Effect of protein binding on penetration of β-lactams into rabbit peripheral lymph. Antimicrob Agents Chemother 1995; 39: 2678–83.

    Article  Google Scholar 

  27. Pardridge WM, Sakiyama R, Fierer G. Transport of propranolol and lidocaine through the rat blood-brain barrier. J Clin Invest 1983; 71: 900–8.

    Article  PubMed  CAS  Google Scholar 

  28. Pardridge WM, Mietus LJ. Transport of steroid hormones through the rat blood-brain barrier: primary role of albuminbound hormone. J Clin Invest 1979; 64: 145–54.

    Article  PubMed  CAS  Google Scholar 

  29. Spector R. Ceftriaxone pharmacokinetics in the central nervous system. J Pharmacol Exp Ther 1986; 236: 380–3.

    PubMed  CAS  Google Scholar 

  30. Spector R. Advances in understanding the pharmacology of agents used to treat bacterial meningitis. Pharmacology 1990; 41: 113–8.

    Article  PubMed  CAS  Google Scholar 

  31. Dacey RG, Sande MA. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother 1974; 6: 437–41.

    Article  PubMed  CAS  Google Scholar 

  32. Nichterlein T, Kretschmar M, Siegsmund M, et al. Erythromycin is ineffective against Listeria monocytogenes in multidrug resistant cells. J Chemother 1995; 7: 184–8.

    PubMed  CAS  Google Scholar 

  33. Schinkel AH, Smit JJM, van Teilingen O, et al. Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77: 491–502.

    Article  PubMed  CAS  Google Scholar 

  34. Schinkel AH, Wagenaar E, van Deemter L, et al. Absence of the mdrla P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 1995; 96: 1698–705.

    Article  PubMed  CAS  Google Scholar 

  35. Phung-Ba V, Warnery A, Scherman D, et al. Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells. Eur J Pharmacol 1995; 288: 187–92.

    Article  PubMed  CAS  Google Scholar 

  36. Cordon-Cardo C, O’Brien JP, Casals D, et al. Multidrug-resitance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 1989; 86: 695–8.

    Article  PubMed  CAS  Google Scholar 

  37. Pardridge WM. Neuropeptides and the blood-brain barrier. Ann Rev Physiol 1983; 45: 73–82.

    Article  CAS  Google Scholar 

  38. Ghersi-Egea JF, Leninger-Muller B, Suleman G, et al. Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. J Neurochem 1994; 62: 1089–96.

    Article  PubMed  CAS  Google Scholar 

  39. Thea D, Barza M. Use of antibacterial agents in infections of the central nervous system. Infect Dis Clin North Am 1989; 3: 553–70.

    PubMed  CAS  Google Scholar 

  40. Davson H, Segal MB. Physiology of the CSF and blood-brain barriers. Boca Raton (FL): CRC Press, 1996.

    Google Scholar 

  41. Fishman RA, Ransohoff J, Osserman EF. Factors influencing the concentration gradient of protein in cerebrospinal fluid. J Clin Invest 1958; 37: 1419–24.

    Article  PubMed  CAS  Google Scholar 

  42. Weisner B, Bernhardt W. Protein fractions of lumbar, cisternal, and ventricular cerebrospinal fluid. J Neurol Sci 1978; 37: 205–14.

    Article  PubMed  CAS  Google Scholar 

  43. Blaney SM, Daniel MJ, Harker AJ, et al. Pharmacokinetics of lamivudine and BCH-189 in plasma and cerebrospinal fluid of nonhuman primates. Antimicrob Agents Chemother 1995; 39: 2779–82.

    Article  PubMed  CAS  Google Scholar 

  44. Chandrasekar PH, Rolston KVI, Smith BR, et al. Diffusion of ceftriaxone into the cerebrospinal fluid of adults. J Antimicrob Chemother 1984; 14: 427–30.

    Article  PubMed  CAS  Google Scholar 

  45. Wellman WE, Dodge HW, Heilman FR, et al. Concentrations of antibiotics in the brain. J Lab Clin Med 1954; 43: 275–9.

    PubMed  CAS  Google Scholar 

  46. Wise BL, Perkins RK, Stevenson E, et al. Penetration of C14sslabelled mannitol from serum into cerebrospinal fluid and brain. Exp Neurol 1964; 10: 264–70.

    Article  PubMed  CAS  Google Scholar 

  47. Nau R, Zysk G, Thiel A, et al. Pharmacokinetic quantification of the exchange of drugs between blood and cerebrospinal fluid in man. Eur J Clin Pharmacol 1993; 45: 469–75.

    Article  PubMed  CAS  Google Scholar 

  48. Shapiro WR, Young DF, Mehta PM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 1975; 293: 161–6.

    Article  PubMed  CAS  Google Scholar 

  49. Fenstermacher JD, Blasberg RG, Patlak CS. Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 1981; 14: 217–48.

    Article  PubMed  CAS  Google Scholar 

  50. Sawchuk RJ, Hedaya MA. Modeling the enhanced uptake of zidovudine (AZT) into cerebrospinal fluid: I. Effect of probenecid. Pharm Res 1990; 7: 332–8.

    Article  PubMed  CAS  Google Scholar 

  51. Mann JD, Butler AB, Johnson RN, et al. Clearance of macrmolecular and particulate substances from the cerebrospinal fluid system of the rat. J Neurosurg 1979; 50: 343–8.

    Article  PubMed  CAS  Google Scholar 

  52. Nilsson C, Stahlberg F, Thomsen C, et al. Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging. Am J Physiol 1992; 262: R20–4.

    PubMed  CAS  Google Scholar 

  53. Nau R, Prange HW. Estimation of steady state antibiotic concentration in cerebrospinal fluid from single-dose kinetics. Eur J Clin Pharmacol 1996; 49: 407–9.

    Article  PubMed  CAS  Google Scholar 

  54. Quagliarello V, Ma A, Stukenbrok H, et al. Ultrastructural localization of albumin transport across the cerebral microvas-culature during experimental meningitis in the rat. J Exp Med 1991; 174: 657–72.

    Article  PubMed  CAS  Google Scholar 

  55. Scheid WM, Dacey RG, Winn HR, et al. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis: alterations with penicillin and methylprednisolone. J Clin Invest 1980; 66: 243–53.

    Article  Google Scholar 

  56. De Vries HE, Kuiper J, de Boer AG, et al. The blood-brain barrier in neuroinflammatory diseases. Pharmacol Rev 1997; 49: 143–55.

    PubMed  Google Scholar 

  57. Reiber H, Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 1987; 163: 319–28.

    Article  PubMed  CAS  Google Scholar 

  58. Bitsch A, Prange H, Jansen J, et al. Häufige Probleme bei der antibiotischen Chemotherapie bakterieller ZNS-Erkrankungen — Fallbeispiele und Vorschläge für die Initialbehandlung. Nervenarzt 1997; 68: 331–5.

    Article  PubMed  CAS  Google Scholar 

  59. Lee BL, Padula AM, Kimbrough RC, et al. Infectious complications with respiratory pathogens despite ciprofloxacin therapy. N Engl J Med 1991; 325: 520–1.

    Article  PubMed  CAS  Google Scholar 

  60. Wispelwey B, Dacey RG, Scheid WM. Brain abscess. In: Scheid WM, Whitley RJ, Durack DT, editors. Infections of the central nervous system. 2nd ed. Philadelphia: Lippincott-Raven, 1997: 463–93.

    Google Scholar 

  61. Britt RH, Enzmann DR. Clinical stages of human brain abscesses on serial CT scans after contrast infusion. J Neurosurg 1983; 59: 972–89.

    Article  PubMed  CAS  Google Scholar 

  62. Odio C, Mohs E, Sklar FH, et al. Adverse reactions to vancomycin used as prophylaxis for CSF shunt procedures. Am J Dis Child 1984; 138: 17–9.

    PubMed  CAS  Google Scholar 

  63. Schmidt T, Froula J, Täuber MG. Clarithromycin lacks bactericidal activity in cerebrospinal fluid in experimental pneumococcal meningitis. J Antimicrob Chemother 1993; 32: 627–32.

    Article  PubMed  CAS  Google Scholar 

  64. Wallace JF, Smith RH, Garcia M, et al. Antagonism between penicillin and chloramphenicol in experimental pneumococcal meningitis. Antimicrob Agents Chemother 1965; 5: 439–44.

    PubMed  CAS  Google Scholar 

  65. Small PM, Täuber MG, Hackbarth CJ, et al. Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits. Infect Immun 1986; 52: 484–7.

    PubMed  CAS  Google Scholar 

  66. Scheid WM. Theoretical and practical considerations of antibiotic therapy for bacterial meningitis. Pediatr Infect Dis 1985; 4: 74–80.

    Article  Google Scholar 

  67. Nau R, Schmidt T, Kaye K, et al. Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits. Antimicrob Agents Chemother 1995; 39: 593–7.

    Article  PubMed  CAS  Google Scholar 

  68. Nau R, Zysk G, Schmidt H, et al. Trovafloxacin delays the antibiotic-induced inflammatory response in experimental pneumococcal meningitis. J Antimicrob Chemother 1997; 39: 781–8.

    Article  PubMed  CAS  Google Scholar 

  69. Strausbaugh LJ, Sande MA. Factors influencing the therapy of experimental Proteus mirabilis meningitis in rabbits. J Infect Dis 1978; 137: 251–60.

    Article  PubMed  CAS  Google Scholar 

  70. Tanaka M, Hoshino K, Hohmura M, et al. Effect of growth conditions on antimicrobial activity of DU-6859a and its bactericidal activity determined by the killing curve method. J Antimicrob Chemother 1996; 37: 1091–102.

    Article  PubMed  CAS  Google Scholar 

  71. Jones RN, Barry AL. Antimicrobial activity of ceftriaxone, cefotaxime, desacetylcefotaxime, and cefotaxime-desacetylcefotaxime in the presence of human serum. Antimicrob Agents Chemother 1987; 31: 818–20.

    Article  PubMed  CAS  Google Scholar 

  72. Täuber MG, Doroshow CA, Hackbarth CJ, et al. Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae. J Infect Dis 1984; 149: 568–74.

    Article  PubMed  Google Scholar 

  73. Schaad UB, McCracken GH, Loock CA, et al. Pharmacokinetics and bacteriological efficacy of moxalactam, cefotaxime, cefoperazone, and rocephin in experimental bacterial meningitis. J Infect Dis 1981; 143: 156–63.

    Article  PubMed  CAS  Google Scholar 

  74. Vogelman B, Gudmundsson S, Leggett J, et al. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis 1988; 158: 831–47.

    Article  PubMed  CAS  Google Scholar 

  75. Drusano GL, Johnson DE, Rosen M, et al. Pharmacodynamics of a fluoroquinolone antimicrobial agent in a neutropenic rat model of Pseudomonas sepsis. Antimicrob Agents Chemother 1993; 37: 483–90.

    Article  PubMed  CAS  Google Scholar 

  76. Sande MA, Korzeniowski OM, Allegro GM, et al. Intermittent or continuous therapy of experimental meningitis due to Streptococcus pneumoniae in rabbits: preliminary observations on the post-antibiotic effect in vivo. Rev Infect Dis 1981; 3: 98–109.

    Article  PubMed  CAS  Google Scholar 

  77. Lutsar I, Ahmed A, Friedland IR, et al. Pharmacodynamics and bactericidal activity of ceftriaxone therapy in experimental cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1997; 41: 2414–7.

    PubMed  CAS  Google Scholar 

  78. Trostdorf F, Reinert RR, Schmidt H, et al. RP59500 for experimental pneumococcal meningitis [poster B-78]. 37th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28–Oct 1; Toronto.

    Google Scholar 

  79. Reesor C, Chow AW, Kureishi A, et al. Kinetics of intraventricular vancomycin in infections of cerebrospinal fluid shunts. J Infect Dis 1988; 158: 1142–3.

    Article  PubMed  CAS  Google Scholar 

  80. Kaiser AB, McGee ZA. Aminoglycoside therapy of gram negative bacillary meningitis. N Engl J Med 1975; 293: 1215–20.

    Article  PubMed  CAS  Google Scholar 

  81. Wen DY, Bottini AG, Hall WA, et al. Infections in neurologic surgery. The intraventricular use of antibiotics. Neurosurg Clin North Am 1992; 3: 343–54.

    CAS  Google Scholar 

  82. Bayston R, Hart CA, Barnicoat M. Intraventricular vancomycin in the treatment of ventriculitis associated with cerebrospinal fluid shunting and drainage. J Neurol Neurosurg Psychiatry 1987; 50: 1419–23.

    Article  PubMed  CAS  Google Scholar 

  83. Lee TK, Kerr RS, Adams CB. Persistent CSF leukocytosis associated with intrathecal gentamycin. Br J Neurosurg 1989; 3: 517–9.

    Article  PubMed  CAS  Google Scholar 

  84. Scheid WM. Drug delivery to the central nervous system: general principles and relevance to therapy for infections of the central nervous system. Rev Infect Dis 1989; 11 Suppl. 7: S1669–90.

    Google Scholar 

  85. Bollensen E, Menck S, Buzanoski J, et al. Iatrogenic epidural spinal abscess. Clin Invest 1993; 71: 780–6.

    Article  CAS  Google Scholar 

  86. Viladrich PF, Cabellos C, Pallares R, et al. High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins. Antimicrob Agents Chemother 1996; 40: 218–20.

    PubMed  CAS  Google Scholar 

  87. Friedland IR, Klugman KP. Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with highdosage cefotaxime. Antimicrob Agents Chemother 1997; 41: 1888–91.

    PubMed  CAS  Google Scholar 

  88. Schaad UB, Wedgwood-Krucko J, Tschaeppeler H. Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet 1988; II: 1411–3.

    Article  Google Scholar 

  89. Sjölin J, Eriksson N, Arneborn P, et al. Penetration of cefotaxime and desacetylcefotaxime into brain abscesses in humans. Antimicrob Agents Chemother 1991; 35: 2606–10.

    Article  PubMed  Google Scholar 

  90. Wong VK, Wright HT, Ross LA, et al. Imipenem/cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J 1991; 10: 122–5.

    Article  PubMed  CAS  Google Scholar 

  91. Klugman KP, Dagan R and the Meropenem Meningitis Study Group. Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Antimicrob Agents Chemother 1995; 39: 1140–6.

    Article  PubMed  CAS  Google Scholar 

  92. Saez-Llorens X, Castano E, Garcia R, et al. Prospective randomized comparison of cefepime and cefotaxime for treatment of bacterial meningitis in infants and children. Antimicrob Agents Chemother 1995; 39: 937–40.

    Article  PubMed  CAS  Google Scholar 

  93. Schmutzhard E, Williams KJ, Vukmirovits G, et al. A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. J Antimicrob Chemother 1995; 36 Suppl. A: 85–97.

    Article  PubMed  CAS  Google Scholar 

  94. Schaad UB, Suter S, Gianella-Borradori A, et al. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 1990; 322: 141–7.

    Article  PubMed  CAS  Google Scholar 

  95. Viladrich PF, Gudiol F, Linares J, et al. Evaluation of vancomycin for therapy of adult pneumococcal meningitis. Antimicrob Agents Chemother 1991; 35: 2467–72.

    Article  PubMed  CAS  Google Scholar 

  96. McCracken GH, Mize SG. A controlled study of intrathecal antibiotic therapy in gram-negative enteric meningitis of infancy. J Pediatr 1976; 89: 66–72.

    Article  PubMed  Google Scholar 

  97. Isaacs D, Slack MPE, Wilkinson AR, et al. Successful treatment of Pseudomonas ventriculitis with ciprofloxacin. J Anti-microb Chemother 1986; 17: 535–8.

    Article  CAS  Google Scholar 

  98. Millar MR, Bransby-Zachary MA, Tompkins DS, et al. Ciprofloxacin for Pseudomonas aeruginosa meningitis. Lancet 1986; I: 1325.

    Article  Google Scholar 

  99. Simon C, Stille W. Antibiotika-Therapie in Klinik und Praxis. 9th ed. Stuttgart: Schattaner, 1997.

    Google Scholar 

  100. Tarasi A, Dever LL, Tomasz A. Activity of quinupristin/ dalfopristin against Streptococcus pneumoniae in vitro and in vivo in the rabbit model of experimental meningitis. J Antimicrob Chemother 1997; 39 Suppl. A: 121–7.

    Article  PubMed  CAS  Google Scholar 

  101. Stuertz K, Schmidt H, Eiffert H, et al. Differential release of lipoteichoic and teichoic acids from Streptococcus pneumoniae as a result of exposure to β-lactam antibiotics, rifa-mycins, trovafloxacin, and quinupristin-dalfopristin. Antimicrob Agents Chemother 1998; 42: 277–81.

    Article  PubMed  CAS  Google Scholar 

  102. Friedman CA, Lovejoy FC, Smith AL. Chloramphenicol disposition in infants and children. J Pediatr 1979; 95: 1071–7.

    Article  PubMed  CAS  Google Scholar 

  103. Kramer PW, Griffith RS, Campbell RL. Antibiotic penetration of the brain. J Neurosurg 1969; 31: 295–302.

    Article  PubMed  CAS  Google Scholar 

  104. Peltola H, Anttila M, Renkonen O-V. Randomized comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Lancet 1989; I: 1281–7.

    Article  Google Scholar 

  105. Friedland IR, Klugman KP. Failure of chloramphenicol therapy in penicillin-resistant pneumococcal meningitis. Lancet 1992; 339: 405–8.

    Article  PubMed  CAS  Google Scholar 

  106. Friedrich LV, White RL, Reboli AC. Pharmacodynamics of trimethoprim-sulfamethoxazole in Listeria meningitis: a case report. Pharmacotherapy 1990; 10: 301–4.

    PubMed  CAS  Google Scholar 

  107. Kawaler B, Hof H. Murine model for therapy of listeriosis in the compromised host: IV. Cotrimoxazole. Chemotherapy 1985; 31: 366–71.

    Article  PubMed  CAS  Google Scholar 

  108. Merle-Melet M, Dossou-Gbete L, Maurer P, et al. Is amoxicillincotrimoxazole the most appropriate antibiotic regimen for listeria meningoencephalitisl Review of 22 cases and the literature. J Infect 1996; 33: 79–85.

    Article  PubMed  CAS  Google Scholar 

  109. Ingham HR, Selkon JB, Roxby CM. Bacteriological study of otogenic cerebral abscesses: chemotherapeutic role of metronidazole. BMJ 1977; 2: 991–3.

    Article  PubMed  CAS  Google Scholar 

  110. Hoffmann HG, Förster D, Muirhead B. Metronidazol- Konzentration im Liquor bei gering entzündeten Meningen. Arzneimittel Forschung Drug Res 1984; 34: 830–1.

    CAS  Google Scholar 

  111. Nau R, Kaye K, Sachdeva M, et al. Rifampin for experimental pneumococcal meningitis. Antimicrob Agents Chemother 1994; 38: 1186–9.

    Article  PubMed  CAS  Google Scholar 

  112. Schmidt H, Zysk G, Reinert RR, et al. Rifabutin for experimental pneumococcal meningitis. Chemotherapy 1997; 43: 264–71.

    Article  PubMed  CAS  Google Scholar 

  113. Paris MM, Hickey SM, Uscher MI, et al. Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1994; 38: 1320–4.

    Article  PubMed  CAS  Google Scholar 

  114. O’Keefe PT, Bayston R. Pneumococcal meningitis in a child with a ventriculo-peritoneal shunt. J Infect 1991; 22: 77–9.

    Article  Google Scholar 

  115. Ring JC, Cates KL, Belani KK, et al. Rifampin for CSF shunt infections caused by coagulase-negative staphylococci. J Pediatr 1979; 95: 317–9.

    Article  PubMed  CAS  Google Scholar 

  116. Ellard GA, Humphries MJ, Gabriel M, et al. Penetration of pyrazinamide into the cerebrospinal fluid in tuberculous meningitis. BMJ 1987; 294: 284–5.

    Article  PubMed  CAS  Google Scholar 

  117. Phuapradit P, Supmonchai K, Mokkhavesa C. The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis. J Neurol Neurosurg Psychiatry 1990; 53: 81–2.

    Article  PubMed  CAS  Google Scholar 

  118. Ellard GA, Humphries MJ, Allen BW. Cerebrospinal fluid drag concentrations and the treatment of tuberculous meningitis. Am Rev Respir Dis 1993; 148: 650–5.

    Article  PubMed  CAS  Google Scholar 

  119. Forgan-Smith R, Ellard GA, Newton D, et al. Pyrazinamide and other drags in tuberculous meningitis. Lancet 1973; II: 374.

    Article  Google Scholar 

  120. Holdiness MR. Cerebrospinal fluid pharmacokinetics of antituberculosis drags. Clin Pharmacokinet 1985; 10: 532–4.

    Article  PubMed  CAS  Google Scholar 

  121. Holdiness MR. Management of tuberculous meningitis. Drags 1990; 39: 224–33.

    Article  CAS  Google Scholar 

  122. Mustafa MM, Ramilo O, Mertsola J, et al. Modulation of inflammation and cachectin activity in relation to treatment of experimental Haemophilus influenzae type b meningitis. J Infect Dis 1989; 160: 818–25.

    Article  PubMed  CAS  Google Scholar 

  123. Tuomanen E, Liu H, Hengstler B, et al. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis 1985; 151: 859–68.

    Article  PubMed  CAS  Google Scholar 

  124. Burroughs M, Rozdzinski E, Geelen S, et al. Astracture-activity relationship for induction of meningeal inflammation by muramyl peptides. J Clin Invest 1993; 92: 297–302.

    Article  PubMed  CAS  Google Scholar 

  125. Riesenfeld-Orn I, Wolpe S, Garcia-Bustos JF, et al. Production of interleukin-1 but not tumor necrosis factor by human monocytes stimulated with pneumococcal cell surface components. Infect Immun 1989; 57: 1890–3.

    PubMed  CAS  Google Scholar 

  126. Kim YS, Kennedy S, Täuber MG. Toxicity of Streptococcus pneumoniae in neurons, astrocytes, and microglia in vitro. J Infect Dis 1995; 171: 1363–8.

    Article  PubMed  CAS  Google Scholar 

  127. Dodge PR, Swartz MN. Bacterial meningitis: a review of selected aspects. II. Special neurologic problems, postmeningitic complications and clinicopathological correlations. N Engl J Med 1965; 272: 954–60 & 1003–10.

    Article  PubMed  CAS  Google Scholar 

  128. Syrogiannopoulos GA, Hansen EJ, Erwin AL, et al. Haemophilus influenzae Type b lipooligosaccharide induces meningeal inflammation. J Infect Dis 1988; 157: 237–44.

    Article  PubMed  CAS  Google Scholar 

  129. Täuber MG, Shibl AM, Hackbarth CJ, et al. Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits. J Infect Dis 1987; 156: 456–62.

    Article  PubMed  Google Scholar 

  130. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991; 324: 1525–31.

    Article  PubMed  CAS  Google Scholar 

  131. Zysk G, Brück W, Gerber J, et al. Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyms in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 1996; 55: 722–8.

    Article  PubMed  CAS  Google Scholar 

  132. Cabellos C, Martinez-Lacasa J, Martos A, et al. Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis. Antimicrob Agents Chemother 1995; 39: 2158–60.

    Article  PubMed  CAS  Google Scholar 

  133. Kourtopoulos H, Holm SE, Norrby R. The influence of steroids on the penetration of antibiotics into brain tissue and brain abscesses. J Antimicrobial Chemother 1983; 11: 245–9.

    Article  CAS  Google Scholar 

  134. Friedland IR, Paris M, Ehrett S, et al. Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemotherapy 1993; 37: 1630–6.

    Article  CAS  Google Scholar 

  135. Schmidt H, Dalhoff A, Stuertz K, et al. Moxifloxacin in the therapy of esperimentai pheumococcal memingitis. Anti-mircob Agents Chemother 1998; 42: 1397–401.

    CAS  Google Scholar 

  136. Mason DJ, Power EGM, Talsania H, et al. Antibacterial action of ciprofloxacin. Antimicrob Agents Chemother 1995; 39: 2752–8.

    Article  PubMed  CAS  Google Scholar 

  137. Dofferhoff ASM, Nijland JH, de Vries-Hospers HG, et al. Effects of different types and combinations of antimicrobial agents on endotoxin release from Gram-negative bacteria: an in-vitro and in-vivo study. Scand J Infect Dis 1991; 23: 745–54.

    Article  PubMed  CAS  Google Scholar 

  138. Jackson JJ, Kropp H. β-lactam antibiotic-induced release of free endotoxin: in-vitro comparison of penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime. J Infect Dis 1992; 165: 1033–41.

    Article  PubMed  CAS  Google Scholar 

  139. Prins JM, Kuijper EJ, Mevissen ML, et al. Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. Infect Immun 1995; 63: 2236–42.

    PubMed  CAS  Google Scholar 

  140. Evans ME, Pollack M. Effect of antibiotic class and concentration on the release of lipopolysaccharide from Escherichia coli. J Infect Dis 1993; 167: 1336–43.

    Article  PubMed  CAS  Google Scholar 

  141. Friedland IR, Jafari H, Ehrett S, et al. Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis. J Infect Dis 1993; 168: 657–62s.

    Article  PubMed  CAS  Google Scholar 

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Nau, R., Sörgel, F. & Prange, H.W. Pharmacokinetic Optimisation of the Treatment of Bacterial Central Nervous System Infections. Clin Pharmacokinet 35, 223–246 (1998). https://doi.org/10.2165/00003088-199835030-00005

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