Abstract
This review considers the five major principles governing optimal dosing ofβ-lactam antibiotics in therapy for bacterial meningitis: (1) the entry or passage of antibiotics into CSF, (2) the antimicrobial activity ofβ-lactams within the purulent CSF in vivo, (3) the bactericidal activity within the CSF, (4) the route and mode of drug administration together with the postantibiotic effect, and (5) the duration of therapy. Special attention is paid to the third principle, bactericidal activity within the CSF, employing the model of the newer, third-generation cephalosporins used in the treatment of meningitis caused by gram-negative aerobic bacilli.
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Sande, M. A.: Antibiotic therapy of bacterial meningitis: Lessons we've learned. American Journal of Medicine 1981, 71: 507–510.
Norrby, R.: A review of the penetration of antibiotics into CSF and its clinical significance. Scandinavian Journal of Infectious Disease 1978, Supplement 14: 296–309.
Norrby, R.: Penetration of antimicrobial agents into cerebrospinal fluid: Pharmacokinetics and clinical aspects. In: Wood, J. H. (ed.): Neurobiology of cerebrospinal fluid. Plenum Press, New York, 1980, p. 449–463.
Norrby, R.: Pharmacokinetic aspects of the treatment of infections of the central nervous system. Journal of Antimicrobial Chemotherapy 1979, 5: 630–633.
Everett, E. D., Strausbaugh, L. J.: Antimicrobial agents and the central nervous system. Neurosurgery 1980, 6: 691–714.
Sande, M. A.: Factors influencing the penetration and activity of antibiotics in experimental meningitis. Journal of Infection 1981, 3, Supplement 1: 33–38.
Sande, M. A., Sherertz, R. J., Zak, O., Dacey, R. G. Jr., Strausbaugh, L. J.: Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals. Scandinavian Journal of Infectious Diseases 1978, Supplement 14: 160–163.
Richards, M. L., Prince, R. A., Kenaley, K. A., Johnson, J. A., LeFrock, J. L.: Antimicrobial penetration into cerebrospinal fluid. Drug Intelligence and Clinical Pharmacy 1981, 15: 341–368.
Bradbury, M.: The concept of the blood-brain barrier. John Wiley and Sons, Chichester, U.K., 1979, p. 1–368.
Rappaport, S. I.: The blood-brain barrier in physiology and medicine. Raven Press, New York, 1976, p. 139–140, 178–182.
Scheld, W. M.: Pathophysiologic correlates in bacterial meningitis. Journal of Infection 1981, 3, Supplement 1: 5–19.
Oppenheimer, S., Beaty, H. N., Petersdorf, R. G.: Pathogenesis of meningitis VII. Cerebrospinal fluid and blood concentrations of methicillin, cephalotin, and cephaloridine in experimental pneumococcal meningitis. Journal of Laboratory and Clinical Medicine 1969, 73: 535–542.
Thrupp, L. D., Leedom, J. M., Ivler, D., Wehrle, P. F., Portnoy, B., Mathies, A. W.: Ampicillin levels in cerebrospinal fluid during treatment of bacterial meningitis. Antimicrobial Agents and Chemotherapy 1966, 1965: 203–216.
Plorde, J. J., Garcia, M., Petersdorf, R. G.: Studies on the pathogenesis of meningitis IV. Penicillin levels in the cerebrospinal fluid in experimental meningitis. Journal of Laboratory and Clinical Medicine 1965, 64: 960–969.
Beam, T. R. Jr., Allen, J. C.: Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges. Antimicrobial Agents and Chemotherapy 1977, 12: 710–716.
Muller, C., Netland, A., Dawson, A. F., Andrew, E.: The penetration of cefuroxime into the cerebrospinal fluid through inflamed and non-inflamed meninges. Journal of Antimicrobial Chemotherapy 1980, 6: 279–283.
Krontz, D. P., Strausbaugh, L. J.: Effect of meningitis and probenecid on the penetration of vancomycin into cerebrospinal fluid in rabbits. Antimicrobial Agents and Chemotherapy 1980, 18: 882–886.
Humbert, G., Leroy, A., Rogez, J. P., Cherubin, C.: Cefoxitin concentrations in the cerebrospinal fluids of patients with meningitis. Antimicrobial Agents and Chemotherapy 1980, 17: 675–678.
Hieber, J. P., Nelson, J. D.: A pharmacologic evaluation of penicillin in children with purulent meningitis. New England Journal of Medicine 1977, 297: 410–413.
Craft, J. C., Feldman, W. E., Nelson, J. D.: Clinico-pharmacological evaluation of amoxicillin and probenecid against bacterial meningitis. Antimicrobial Agents and Chemotherapy 1979, 16: 346–352.
Feldman, W. E., Moffitt, S., Manning, N. S.: Penetration of cefoxitin into cerebrospinal fluid of infants and children with bacterial meningitis. Antimicrobial Agents and Chemotherapy 1982, 21: 468–471.
Nolan, C. M., McAllister, C. K., Walters, E., Beaty, H. N.: Experimental pneumococcal meningitis IV. The effect of methylprednisolone on meningeal inflammation. Journal of Laboratory and Clinical Medicine 1978, 91: 979–988.
Scheld, W. M., Brodeur, J. P.: Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal andEscherichia coli meningitis. Antimicrobial Agents and Chemotherapy 1983, 23: 108–112.
Lerner, P. I.: Selection of antimicrobial agents in bacterial infections of the central nervous system. Advances in Neurology 1964, 6: 169–195.
Barlow, C. F.: Clinical aspects of the blood-brain barrier. Annual Review of Medicine 1964, 15: 187–205.
Taber, L. H., Yow, M. D., Nieberg, F. G.: The penetration of broad-spectrum antibiotics into the cerebrospinal fluid. Annals of the New York Academy of Sciences 1967, 145: 437–451.
Rall, D. P., Stabenau, J. R., Zubrud, C. G.: Distribution of drugs between blood and cerebrospinal fluid: general methodology and effects of pH gradients. Journal of Pharmacology and Experimental Therapeutics 1959, 125: 185–193.
Barza, M., Brown, R. B., Shanks, C., Gamble, C., Weinstein, L.: Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline and oxytetracycline in dogs. Antimicrobial Agents and Chemotherapy 1975, 6: 713–720.
Fishman, R. A.: Blood-brain and CSF barriers to penicillin and related organic acids. Archives of Neurology 1966, 15: 113–124.
Lorenzo, A. V., Spector, R.: The distribution of drugs in the central nervous system. Advances in Experimental Medicine and Biology 1976, 69: 447–462.
Kunin, C. M.: Effect of serum binding on the distribution of penicillin in the rabbit. Journal of Laboratory and Clinical Medicine 1965, 65: 406–412.
Ruedy, J.: The concentration of penicillins in the cerebrospinal fluid and brain of rabbits with experimental meningitis. Canadian Journal of Physiology and Pharmacology 1965, 43: 763–772.
Straussbaugh, L. J., Murray, T. W., Sande, M. A.: Comparative penetration of six antibiotics into the cerebrospinal fluid of rabbits with experimental staphylococcal meningitis. Journal of Antimicrobial Chemotherapy 1980, 6: 363–371.
Dixon, R. L., Owens, E. S., Rail, D. P.: Evidence of active transport of benzy-14C-penicillin from cerebrospinal fluid to blood. Journal of Pharmacological Sciences 1969, 58: 1106–1109.
Pollay, M.: Transport mechanisms in the choroid plexus. Federation Proceedings 1974, 33: 2064–2069.
Spector, R., Lorenzo, A. V.: The effect of salicylate and probenicid on the cerebrospinal fluid transport of penicillin, aminosalicylic acid, and iodide. Journal of Pharmacology and Experimental Therapeutics 1974, 188: 55–65.
Spector, R., Lorenzo, A. V.: Inhibition of penicillin transport from cerebrospinal fluid after intracisternal inoculation of bacteria. Journal of Clinical Investigation 1974, 54: 316–323.
Dacey, R. G. Jr., Sande, M. A.: Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrobial Agents and Chemotherapy 1974, 6: 437–441.
Krontz, D. P., Strausbaugh, L. J.: Effect of meningitis and probenecid on the penetration of vancomycin into cerebrospinal fluid in rabbits. Antimicrobial Agents and Chemotherapy 1980, 18: 882–886.
Beam, T. R. Jr., Allen, J. C.: Assessment of antibiotic efficacy in acute bacterial meningitis. Clinical Pharmacology and Therapeutics 1979, 25: 199–203.
Overturf, G. D., Steinberg, E. A., Underman, A. E., Wilkins, J., Leedom, J. M., Mathies, A. W. Jr., Wehile, P. F.: Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis. Antimicrobial Agents and Chemotherapy 1977, 11: 420–426.
Korzeniowski, O. M., Carvalho, E. M. Jr., Rocha, H., Sande, M. A.: Evaluation of cefamandole therapy of patients with bacterial meningitis. Journal of Infectious Diseases 1978, 137: S169-S179.
Swedish Study Group: Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis. Lancet 1982, i: 295–299.
Turk, D. C.: A comparison of chloramphenicol and ampicillin as bactericidal agents forHaemophilus influenzae type B. Journal of Medical Microbiology 1977, 10: 127–131.
Rahal, J. J. Jr., Simberkoff, M. S.: Bactericidal and bacteriostatic action of chloramphenicol against meningeal pathogens. Antimicrobial Agents and Chemotherapy 1979, 16: 13–18.
Feder, H. M. Jr., Osier, C., Maderazo, E. G.: Chloramphenicol: A review of its use in clinical practice. Reviews of Infectious Diseases 1981, 3: 479–491.
Mulhall, A., deLouvois, J., Hurley, R.: Efficacy of chloramphenicol in the treatment of neonatal and infantile meningitis: A study of 70 cases. Lancet 1983, i: 284–287.
Strausbaugh, L. J., Sande, M. A.: Factors influencing the therapy of experimentalProteus mirabilis meningitis in rabbits. Journal of Infectious Diseases 1978, 137: 251–260.
Mangi, R. J., Kundargi, R. S., Quintiliani, R., Andriole, V. T.: Development of meningitis during cephalothin therapy. Annals of Internal Medicine 1973, 78: 347–351.
Lee, C. C., Herr, E. B. Jr., Anderson, R. C.: Pharmacological and toxicological studies on cephalothin. Clinical Medicine 1963, 70: 1123–1138.
Wick, W. E.: In vitro and in vivo laboratory comparison of cephalothin and desacetylcephalothin. Antimicrobial Agents and Chemotherapy 1966, 1965: 870–875.
Nolan, C. M., Ulmer, C. W. Jr.: A study of cephalothin and desacetylcephalothin in cerebrospinal fluid in therapy for experimental pneumococcal meningitis. Journal of Infectious Diseases 1980, 141: 326–330.
Nolan, C. M., Ulmer, C. W. Jr.: Penetration of cefotaxime and moxalactam into cerebrospinal fluid of rabbits with experimentally inducedEscherichia coli meningitis. Reviews of Infectious Diseases 1982, 4: S396-S400.
Lepper, M. H., Dowling, H. F.: Treatment of pneumococcic meningitis with penicillin compared with penicillin plus aureomycin. Studies including observations on an apparent antagonism between penicillin and aureomycin. Archives of Internal Medicine 1951, 88: 489–494.
Mathies, A. W., Leedom, J. M., Ivler, D., Wehrle, P. F., Portnoy, B.: Antibiotic antagonism in bacterial meningitis. Antimicrobial Agents and Chemotherapy 1967, 1966: 218–224.
Wallace, J. F., Smith, R. H., Garcia, M., Petersdorf, R. G.: Studies on the pathogenesis of meningitis IV. Antagonism between penicillin and chloramphenicol in experimental pneumococcal meningitis. Journal of Laboratory and Clinical Medicine 1967, 70: 408–418.
Bodine, J., Murray, T., Sande, M. A.: Combination therapy of experimentalHaemophilus influenzae andStreptococcus pneumoniae meningitis. Clinical Research 1977, 24: 27A.
Cole, F. S., Daum, R. S., Teller, L., Goldman, D. A., Smith, A. L.: Effect of ampicillin and chloramphenicol alone and in combination on ampicillin-susceptible and -resistantHaemophitus influenzae type b. Antimicrobial Agents and Chemotherapy 1979, 15: 415–419.
MacKenzie, A. M. R.: Combined action of chlor-amphenicol and ampicillin onHaemophilus influenzae. Journal of Antimicrobial Chemotherapy 1979, 5: 693–698.
Cherubin, C. E., Marr, J. S., Sierra, M. F., Becker, S.: Listeria and gram-negative bacillary meningitis in New York City, 1972–1979. Frequent causes of meningitis in adults. American Journal of Medicine 1981, 71: 199–209.
Scheld, W. M., Fink, F. N., Fletcher, D. D., Sande, M. A.: Mecillinam-ampicillin synergism in experimentalEnterobacteriaceae meningitis. Antimicrobial Agents and Chemotherapy 1979, 16: 271–276.
Schaad, U. B., Grimm, L. M., Beskid, G., Cleeland, R., Nelson, J. D., McCracken, G. H. Jr.: Mecillinam alone and in combination with ampicillin or moxalactam in experimentalEscherichia coli meningitis. Infection 1982, 10: 92–96.
Scheld, W. M., Brodeur, J. P., Keeley, J. M., Field, M. R., Kelly, W. J. IV, Long, W. J. Jr., Zak, O.: Evaluation of azlocillin in vitro and in discriminative animal models of infection. Journal of Antimicrobial Chemotherapy 1983, 11, Supplement B: 51–68.
Scheld, W. M., Fletcher, D. D., Fink, F. N., Sande, M. A.: Response to therapy in an experimental rabbit model of meningitis due toListeria monocytogenes. Journal of Infectious Diseases 1979, 140: 287–294.
Stamm, A. M., Dismukes, W. E., Simmons, B. P., Cobbs, C. G., Elliott, A., Budrich, P., Harmon, J.: Listeriosis in renal transplant recipients: Reports of an outbreak and review of 102 cases. Reviews of Infectious Diseases 1982, 4: 665–682.
Scheld, W. M., Alliegro, G. M., Field, M. R., Brodeur, J. P.: Synergy between ampicillin and gentamicin in experimental meningitis due to group B streptococci. Journal of Infectious Diseases 1982, 146: 100.
Yogev, R., Kabat, W. J.: Synergistic action of nafcillin and ampicillin against ampicillin-resistantHaemophilus influenzae type b bacteremia and meningitis in infant rats. Antimicrobial Agents and Chemotherapy 1980, 18: 122–124.
Yu, P. K. W., Washington, J. A. II.: Bactericidal activity of cefoperazone with CP-45, 889 against large inocula ofβ-lactamase-producingHaemophilus influenzae. Antimicrobial Agents and Chemotherapy 1981, 20: 63–65.
Feldman, W. E.: Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis. Journal of Pediatrics 1976, 88: 549–552.
Feldman, W. E.: Relation of concentrations of bacteria and bacterial antigen in cerebrospinal fluid to prognosis in patients with bacterial meningitis. New England Journal of Medicine 1977, 296: 433–435.
Bergeron, M. G., Claveau, S., Simard, P.: Limited in vitro activity of cefamandole against 100 beta-lactamase- and non-beta-lactamase-producingHaemophilus influenzae strains: Comparison of moxalactam, chloramphenicol, and ampicillin. Antimicrobial Agents and Chemotherapy 1981, 19: 101–105.
Steinberg, E., Overturf, G. D., Wilkins, J., Braff, L. J., Strent, J. M., Leedom, J. M.: Failure of cefarnandole in treatment of meningitis due toHaemophilus influenzae type b. Journal of Infectious Diseases 1978, 137: S180-S186.
Durack, D. T., Corey, G. R., Perfect, J. R.: Trimethoprim-sulfamethoxazole vs. ampicillin in the treatment of meningitis due toStreptococcus pneumoniae. Reviews of Infectious Diseases 1982, 4: 311–314.
Simberkoff, M. S., Moldover, N. H., Rahal, J. J. Jr.: Absence of detectable bactericidal and opsonic activities in normal and infected cerebrospinal fluids. A regional host defense deficiency. Journal of Laboratory and Clinical Medicine 1980, 95: 362–372.
Zwahlen, A., Nydegger, U. E., Vaudaux, P., Lamberg, P.-H., Waldvogel, F. A.: Complement-mediated opsonic activity in normal and infected human cerebrospinal fluid: Early response during bacterial meningitis. Journal of Infectious Diseases 1982, 145: 635–646.
Rahal, J. J. Jr., Simberkoff, M. S.: Host defense and antimicrobial therapy in adult gram-negative bacillary meningitis. Annals of Internal Medicine 1982, 96: 468–474.
Scheld, W. M., Brodeur, J. P.: Complement-mediated opsonic and bactericidal activity in experimental meningitis. Clinical and Experimental Immunology (in press).
Strausbaugh, L. J., Mandeleris, C. D., Sande, M. A.: Comparison of four aminoglycoside antibiotics in the therapy of experimentalE. coli meningitis. Journal of Laboratory and Clinical Medicine 1977, 89: 692–701.
Scheld, W. M., Brown, R. S. Jr., Sande, M. A.: Comparison of netilmicin with gentamicin in the therapy of experimentalEscherichia coli meningitis. Antimicrobial Agents and Chemotherapy 1978, 13: 899–904.
Schaad, U. B., McCracken, G. H. Jr., Loock, C. A., Thomas, M. L.: Pharmacokinetics and bacteriological efficacy of moxalactam (LY127935), netilmicin, and ampicillin in experimental gram-negative enteric bacillary meningitis. Antimicrobial Agents and Chemotherapy 1980, 17: 406–411.
Scheld, W. M., Sande, M. A.: Bactericidal vs. bacteriostatic antibiotic therapy of experimental pneumococcal meningitis in rabbits. Journal of Clinical Investigation 1983, 71: 411–419.
Armengaud, M., Auvergnat, J-C. H., Nanaet, R., Massip, P., Tho, T. C.: Des concentrations des antibiotiques dans le LCR au cours de traitements de meningitis bacteriennes aigues. Medical Hygiene 1979, 30: 398–401.
Chabbert, Y. A.: Le laboratoire d'antiobiotherapie dans les meningites purulentes. Seminairs Hopital Paris 1967, 43: 239–242.
Landesman, S. H., Corrado, M. L., Shah, P. M., Armengaud, M., Barza, M., Cherubin, C. E.: Past and current rolés for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis. American Journal of Medicine 1981, 71: 693–703.
Marchou, B., Tho, T. V., Armengaud, M.: Diffusion of ceftriaxone (Ro13-9904/001) into the cerebrospinal fluid. Comparison with otherβ-lactam antibiotics in dogs with healthy meninges and in dogs with experimental meningitis. Chemotherapy 1981, 27, Supplement 1: 37–41.
McCracken, G. H. Jr., Nelson, J. D., Grimm, L.: Pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam in experimentalStreptococcus pneumoniae andHaemophilus influenzae meningitis. Antimicrobial Agents and Chemotherapy 1982, 21: 262–267.
McCracken, G. H. Jr., Schaad, U. B.: The pharmacologic basis for moxalactam therapy for gram-negative enteric bacillary meningitis of infancy. Reviews of Infectious Diseases 1982, 4, Supplement: S603-S605.
Schaad, U. B., McCracken, G. H. Jr., Loock, C. A., Thomas, M. L.: Pharmacokinetics and bacteriologic efficacy of moxalactam, cefotaxime, cefoperazone, and rocephin in experimental bacterial meningitis. Journal of Infectious Diseases 1981, 143: 156–163.
Sakata, Y., Boccazzi, A., McCracken, G. H. Jr.: Pharmacokinetics and bacteriological effect of ceftazidime in experimentalStreptococcus pneumoniae, Haemophilus influenzae, andEscherichia coli meningitis. Antimicrobial Agents and Chemotherapy 1983, 23: 213–217.
Scheld, W. M., Brodeur, J. P., Sande, M. A., Alliegro, G. M.: Comparison of cefoperazone with penicillin, ampicillin, gentamicin, and chloramphenicol in the therapy of experimental meningitis. Antimicrobial Agents and Chemotherapy 1982, 22: 652–656.
Delaplane, D., Yogev, R., Shulman, S. T.: Ceftriaxone therapy of group B streptococcal bacteremia and meningitis in infant rants. Journal of Antimicrobial Therapy 1983, 11: 69–73.
DelRio, M., McCracken, G. H. Jr., Nelson, J. D., Chrane, D., Shelton, S.: Phaimacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis. Antimicrobial Agents and Chemotherapy 1982, 22: 622–627.
Kaplan, S. L., Mason, E. O. Jr., Kvernland, S. J., Calaway, E. L., Feigin, R. D.: Pharmacology and cerebrospinal fluid penetration of moxalactam in children and dosage recommendations. Review of Infectious Diseases 1982, 4, Supplement: S597-S602.
Landesman, S. H., Corrado, M. L., Cherubin, C. E., Gombert, M., Cleri, D.: Diffusion of a new beta-lactam (LY127935) into cerebrospinal fluid. Implications for therapy of gram-negative bacillary meningitis. American Journal of Medicine 1980, 69: 92–98.
Modai, J., Wolff, M., LeBas, J., Meulemans, A., Manuel, C.: Moxalactam penetration into cerebrospinal fluid in patients with bacterial meningitis. Antimicrobial Agents and Chemotherapy 1982, 21: 551–553.
Latif, R., Dajani, A. S.: Ceftriaxone diffusion into cerebrospinal fluid of children with meningitis. Antimicrobial Agents and Chemotherapy 1983, 23: 46–48.
Corrado, M. L., Gombert, M., Cherubin, C. E.: Designing appropriate therapy in the treatment of gramnegative bacillary meningitis. Journal of the American Medical Association 1982, 248: 71–74.
Landesman, S. H., Cherubin, C. E., Corrado, M. L.: Gram-negative bacillary meningitis. New therapy and changing concepts. Archives of Internal Medicine 1982, 142: 939–940.
Olson, D. A., Hoeprich, P. D., Nolan, S. M., Goldstein, E.: Successful treatment of gram-negative bacillary meningitis with moxalactam. Annals of Internal Medicine 1981, 95: 302–305.
Cherubin, C. E., Corrado, M. L., Nair, S. R., Gombert, M. E., Landesman, S. H., Humbert, G.: Treatment of gram-negative bacillary meningitis: Role of the new cephalosporin antibiotics. Reviews of Infectious Diseases 1982, 4, Supplement: S453-S464.
Rahal, J. J. Jr.: Moxalactam therapy for gram-negative bacillary meningitis. Reviews of Infectious Diseases 1982, 4, Supplement: S606-S609.
Belohradsky, B. H., Bruch, K., Geiss, D., Kafetzis, D., Marget, W., Peters, G.: Intravenous cefotaxime in children with bacterial meningitis. Lancet 1980, i: 61–63.
Cadoz, M., Denis, F., Felix, H., Diop Mar, I.: Treatment of purulent meningitis with a new cephalosporin-Rocephin (Ro13-9904). Chemotherapy 1981, 27, Supplement 1: 57–61.
Cadoz, M., Denis, F., Guerma, T., Prince-David, M., Diop Mar, I.: Bacteriological, pharmacological and clinical comparison between amoxicillin and ceftriaxone in the treatment of 300 purulent meningitis patients. Pathologic Biology 1982, 30: 522–525.
Uwaydah, M. M., Tannir, N., Kantarjian, H., Osseiran, M., Bal'a, F.: Moxalactam therapy of bacterial meningitis in adults. Antimicrobial Agents and Chemotherapy 1983, 23: 289–292.
Del Rio, M. A., Chrane, D., Shelton, S., McCracken, G. H. Jr., Nelson, J. D.: Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. Lancet 1983, i: 1241–1244.
Neu, H. C.: The new beta-lactamase stable cephalosporins. Annals of Internal Medicine 1982, 97: 408–419.
Khurana, C. M., Deddish, P. A.: Effectiveness of treatment with mezlocillin, ampicillin and latamoxef (moxalactam) of experimental group Bβ-haemolytic streptococcal meningitis in rabbits. Journal of Antimicrobial Chemotherapy 1983, 11: 125–133.
Kourtopoulos, H., Holm, S. E., Norrby, R.: Benzylpenicillin penetration into CSF after different routes of administration in rabbits. Scandinavian Journal of Infectious Diseases 1983, 15: 103–105.
Eagle, H., Fleischmann, R., Levy, M.: “Continuous” vs. “discontinuous” therapy with penicillin. New England Journal of Medicine 1953, 248: 481–488.
Barza, M., Brush, J., Bergeron, M. G., Weinstein, L.: Penetration of antibiotics into fibrin loci in vivo. III. Intermittent vs. continuous infusion and the effects of probenecid. Journal of Infectious Diseases 1974, 129: 73–78.
Plorde, J. J., Garcia, M., Petersdorf, R. G.: Studies on the pathogenesis of meningitis IV. Penicillin levels in the cerebrospinal fluid in experimental meningitis. Journal of Laboratory and Clinical Medicine 1964, 64: 960–969.
McDermott, W.: Microbial persistence. Yale Journal of Biology and Medicine 1958, 30: 257–291.
Sande, M. A., Korzeniowski, O. M., Alliegro, G. M., Brennan, R. O., Zak, O., Scheld, W. M.: Intermittent or continuous therapy of experimental meningitis due toStreptococcus pneumoniae in rabbits: Preliminary observations on the postantibiotic effect in vivo. Reviews of Infectious Diseases 1981, 3: 98–109.
McDonald, P. J., Craig, W. A., Kunin, C. M.: Persistent effect of antibiotics onStaphylococcus aureus after exposure for limited periods of time. Journal of Infectious Diseases 1977, 135: 217–223.
Perfect, J. R., Durack, D. T.: Pharmacokinetics of cefoperazone, moxalactam, cefotaxime, trimethoprim and sulfamethoxazole in experimental meningitis. Journal of Antimicrobial Chemotherapy 1981, 8: 49–58.
MacFarlane, J. T., Anjorin, F. I., Cleland, P. G., Hansson-King, M., Tor-Agbidye, S., Wali, S. S., Weir, W. R. C., Whittle, H. C., Yahaya, H. N., Greenwood, B. M.: Single injection treatment of meningococcal meningitis. I. Long-acting penicillin. Transactions of the Royal Society of Tropical Medicine and Hygiene 1979, 73: 693–687.
Whittle, H. C., Davidson, N. M., Greenwood, B. M., Warrell, D. A., Tomkins, A., Tugwell, P., Zalin, A., Bryceson, A. D. M., Parry, E. H. O., Brueton, M., Duggan, M., Rajkovic, A. D.: Trial of chloramphenicol for meningitis in northern savanna of Africa. British Medical Journal 1973, 2: 379–381.
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Scheld, W.M. Rationale for optimal dosing of beta-lactam antibiotics in therapy for bacterial meningitis. Eur. J, Clin. Microbiol. 3, 579–591 (1984). https://doi.org/10.1007/BF02013629
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DOI: https://doi.org/10.1007/BF02013629