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. 1980 Mar;17(3):406–411. doi: 10.1128/aac.17.3.406

Pharmacokinetics and bacteriological efficacy of moxalactam (LY127935), netilmicin, and ampicillin in experimental gram-negative enteric bacillary meningitis.

U B Schaad, G H McCracken Jr, C A Loock, M L Thomas
PMCID: PMC283800  PMID: 6448576

Abstract

Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beam T. R., Jr, Allen J. C. Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges. Antimicrob Agents Chemother. 1977 Dec;12(6):710–716. doi: 10.1128/aac.12.6.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowman R. L., Silverblatt F. J., Kaloyanides G. J. Comparison of the nephrotoxicity of netilmicin and gentamicin in rats. Antimicrob Agents Chemother. 1977 Oct;12(4):474–478. doi: 10.1128/aac.12.4.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cserr H. F. Physiology of the choroid plexus. Physiol Rev. 1971 Apr;51(2):273–311. doi: 10.1152/physrev.1971.51.2.273. [DOI] [PubMed] [Google Scholar]
  4. Dacey R. G., Sande M. A. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1974 Oct;6(4):437–441. doi: 10.1128/aac.6.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haltalin K. C., Markley A. H., Woodman E. Agar plate dilution method for routine antibiotic susceptibility testing in a hospital laboratory. Am J Clin Pathol. 1973 Sep;60(3):384–394. doi: 10.1093/ajcp/60.3.384. [DOI] [PubMed] [Google Scholar]
  6. LITHANDER A. THE PASSAGE OF PENICILLINS INTO THE CEREBRO-SPINAL FLUID AND BRAIN IN EXPERIMENTAL MENINGITIS--EXPERIMENTAL INVESTIGATIONS ON RABBITS. Postgrad Med J. 1964 Dec;40:SUPPL–SUPPL:119. doi: 10.1136/pgmj.40.suppl.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. McCracken G. H., Jr, Mize S. G. A controlled study of intrathecal antibiotic therapy in gram-negative enteric meningitis of infancy. Report of the neonatal meningitis cooperative study group. J Pediatr. 1976 Jul;89(1):66–72. doi: 10.1016/s0022-3476(76)80929-8. [DOI] [PubMed] [Google Scholar]
  8. Neu H. C., Aswapokee N., Fu K. P., Aswapokee P. Antibacterial activity of a new 1-oxa cephalosporin compared with that of other beta-lactam compounds. Antimicrob Agents Chemother. 1979 Aug;16(2):141–149. doi: 10.1128/aac.16.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Sande M. A., Sherertz R. J., Zak O., Strausbaugh L. J. Cephalosporin antibiotics in therapy of experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis in rabbits. J Infect Dis. 1978 May;137 (Suppl):S161–S168. doi: 10.1093/infdis/137.supplement.s161. [DOI] [PubMed] [Google Scholar]
  10. Scheld W. M., Brown R. S., Jr, Sande M. A. Comparison of netilmicin with gentamicin in the therapy of experimental Escherichia coli meningitis. Antimicrob Agents Chemother. 1978 Jun;13(6):899–904. doi: 10.1128/aac.13.6.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Spector R., Lorenzo A. V. Inhibition of penicillin transport from the cerebrospinal fluid after intracisternal inoculation of bacteria. J Clin Invest. 1974 Aug;54(2):316–325. doi: 10.1172/JCI107767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Strausbaugh L. J., Mandaleris C. D., Sande M. A. Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis. J Lab Clin Med. 1977 Apr;89(4):692–701. [PubMed] [Google Scholar]

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