Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1983 Nov;24(5):682–688. doi: 10.1128/aac.24.5.682

Evaluation of aztreonam in experimental bacterial meningitis and cerebritis.

W M Scheld, J P Brodeur, J C Gratz, P Foresman, G Rodeheaver
PMCID: PMC185925  PMID: 6362552

Abstract

Aztreonam (SQ 26,776), a new monocyclic beta-lactam agent, was compared with ampicillin, ampicillin plus chloramphenicol, and gentamicin in rabbits with experimental meningitis induced by, respectively, ampicillin-susceptible Haemophilus influenzae, ampicillin-resistant H. influenzae, and Escherichia coli. Aztreonam was also compared with gentamicin in experimentally induced E. coli cerebritis in rats. Doses of the various agents were delivered that produced near-peak concentrations in serum comparable to those attained in humans on standard parenteral regimens. The percent penetration [( concentration in cerebrospinal fluid/concentration in serum] X 100) of aztreonam into purulent rabbit cerebrospinal fluid was 23% (versus 12, 27, and 21%, respectively, for ampicillin, chloramphenicol, and gentamicin). In experimental meningitis in vivo, aztreonam was more rapidly bactericidal than was ampicillin in ampicillin-susceptible H. influenzae meningitis, ampicillin or chloramphenicol in ampicillin-resistant H. influenzae meningitis, or gentamicin in E. coli meningitis. In the therapy of experimental cerebritis, the early stage of brain abscess formation, aztreonam reduced the numbers of E. coli in rat brain as rapidly as did gentamicin. Aztreonam deserves further evaluation in acute gram-negative bacterial infections of the central nervous system in both experimental animals and in humans.

Full text

PDF
682

Selected References

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

  1. Alcid D. V., Seligman S. J. Simplified assay for gentamicin in the presence of other antibiotics. Antimicrob Agents Chemother. 1973 May;3(5):559–561. doi: 10.1128/aac.3.5.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker C. N., Thornsberry C., Jones R. N. In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains. Antimicrob Agents Chemother. 1980 Apr;17(4):757–761. doi: 10.1128/aac.17.4.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bannatyne R. M., Cheung R. Chloramphenicol bioassay. Antimicrob Agents Chemother. 1979 Jul;16(1):43–45. doi: 10.1128/aac.16.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bergeron M. G., Claveau S., Simard P. Limited in vitro activity of cefamandole against 100 beta-lactamase- and non-beta-lactamase-producing Haemophilus influenzae strains: comparison of moxalactam, chloramphenicol, and ampicillin. Antimicrob Agents Chemother. 1981 Jan;19(1):101–105. doi: 10.1128/aac.19.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black P., Graybill J. R., Charache P. Penetration of brain abscess by systemically administered antibiotics. J Neurosurg. 1973 Jun;38(6):705–709. doi: 10.3171/jns.1973.38.6.0705. [DOI] [PubMed] [Google Scholar]
  6. Bonner D. P., Whitney R. R., Baughn C. O., Miller B. H., Olsen S. J., Sykes R. B. In-vivo properties of SQ 26,776. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):123–130. doi: 10.1093/jac/8.suppl_e.123. [DOI] [PubMed] [Google Scholar]
  7. Brewer N. S., MacCarty C. S., Wellman W. E. Brain abscess: a review of recent experience. Ann Intern Med. 1975 Apr;82(4):571–576. doi: 10.7326/0003-4819-82-4-571. [DOI] [PubMed] [Google Scholar]
  8. 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. Am J Med. 1981 Aug;71(2):199–209. doi: 10.1016/0002-9343(81)90106-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Fainstein V., Weaver S., Bodey G. P. Comparative in vitro study of SQ26,776. Antimicrob Agents Chemother. 1982 Feb;21(2):294–298. doi: 10.1128/aac.21.2.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feldman W. E. Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis. J Pediatr. 1976 Apr;88(4 Pt 1):549–552. doi: 10.1016/s0022-3476(76)80003-0. [DOI] [PubMed] [Google Scholar]
  12. Garfield J. Management of supratentorial intracranial abscess: a review of 200 cases. Br Med J. 1969 Apr 5;2(5648):7–11. doi: 10.1136/bmj.2.5648.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heineman H. S., Braude A. I., Osterholm J. L. Intracranial suppurative disease. Early presumptive diagnosis and successful treatment without surgery. JAMA. 1971 Dec 6;218(10):1542–1547. doi: 10.1001/jama.218.10.1542. [DOI] [PubMed] [Google Scholar]
  14. Ingham H. R., Slekon J. B., Roxby C. M. Bacteriological study of otogenic cerebral abscesses: chemotherapeutic role of metronidazole. Br Med J. 1977 Oct 15;2(6093):991–993. doi: 10.1136/bmj.2.6093.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kramer P. W., Griffith R. S., Campbell R. L. Antibiotic penetration of the brain. A comparative study. J Neurosurg. 1969 Sep;31(3):295–302. doi: 10.3171/jns.1969.31.3.0295. [DOI] [PubMed] [Google Scholar]
  16. Landesman S. H., Corrado M. L., Shah P. M., Armengaud M., Barza M., Cherubin C. E. Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis. Am J Med. 1981 Oct;71(4):693–703. doi: 10.1016/0002-9343(81)90240-0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. McCracken G. H., Jr, Mize S. G., Threlkeld N. Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the Second Neonatal Meningitis Cooperative Study Group. Lancet. 1980 Apr 12;1(8172):787–791. [PubMed] [Google Scholar]
  19. Mendes M., Moore P., Wheeler C. B., Winn H. R., Rodeheaver G. Susceptibility of brain and skin to bacterial challenge. J Neurosurg. 1980 Jun;52(6):772–775. doi: 10.3171/jns.1980.52.6.0772. [DOI] [PubMed] [Google Scholar]
  20. Neu H. C., Labthavikul P. Antibacterial activity of a monocyclic beta-lactam SQ 26,776. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):111–122. doi: 10.1093/jac/8.suppl_e.111. [DOI] [PubMed] [Google Scholar]
  21. Norrby R., Friberg K., Holm S. E. In-vitro antibacterial activity of SQ 26,776. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):69–76. doi: 10.1093/jac/8.suppl_e.69. [DOI] [PubMed] [Google Scholar]
  22. Olson D. A., Hoeprich P. D., Nolan S. M., Goldstein E. Successful treatment of gram-negative bacillary meningitis with moxalactam. Ann Intern Med. 1981 Sep;95(3):302–305. doi: 10.7326/0003-4819-95-3-302. [DOI] [PubMed] [Google Scholar]
  23. Perfect J. R., Durack D. T. Pharmacokinetics of cefoperazone, moxalactam, cefotaxime, trimethoprim and sulphamethoxazole in experimental meningitis. J Antimicrob Chemother. 1981 Jul;8(1):49–58. doi: 10.1093/jac/8.1.49. [DOI] [PubMed] [Google Scholar]
  24. Phillips I., King A., Shannon K., Warren C. SQ 26,776: in-vitro antibacterial activity and susceptibility to beta-lactamases. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):103–110. doi: 10.1093/jac/8.suppl_e.103. [DOI] [PubMed] [Google Scholar]
  25. Rahal J. J., Jr, Simberkoff M. S. Bactericidal and bacteriostatic action of chloramphenicol against memingeal pathogens. Antimicrob Agents Chemother. 1979 Jul;16(1):13–18. doi: 10.1128/aac.16.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rahal J. J., Simberkoff M. S. Host defense and antimicrobial therapy in adult gram-negative bacillary meningitis. Ann Intern Med. 1982 Apr;96(4):468–474. doi: 10.7326/0003-4819-96-4-468. [DOI] [PubMed] [Google Scholar]
  27. Reeves D. S., Bywater M. J., Holt H. A. Antibacterial activity of the monobactam SQ 26,776 against antibiotic resistant enterobacteria, including Serratia spp. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):57–68. doi: 10.1093/jac/8.suppl_e.57. [DOI] [PubMed] [Google Scholar]
  28. Roberts M. C., Swenson C. D., Owens L. M., Smith A. L. Characterization of chloramphenicol-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 1980 Oct;18(4):610–615. doi: 10.1128/aac.18.4.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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. J Infect Dis. 1981 Feb;143(2):156–163. doi: 10.1093/infdis/143.2.156. [DOI] [PubMed] [Google Scholar]
  30. 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. Antimicrob Agents Chemother. 1980 Mar;17(3):406–411. doi: 10.1128/aac.17.3.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Scheld W. M., Brodeur J. P., Keeley J. M. Evaluation of mezlocillin in discriminative animal models of infection. J Antimicrob Chemother. 1982 Jan;9 (Suppl A):51–64. doi: 10.1093/jac/9.suppl_a.51. [DOI] [PubMed] [Google Scholar]
  32. Scheld W. M., Fletcher D. D., Fink F. N., Sande M. A. Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. J Infect Dis. 1979 Sep;140(3):287–294. doi: 10.1093/infdis/140.3.287. [DOI] [PubMed] [Google Scholar]
  33. Steinberg E. A., Overturf G. D., Wilkins J., Baraff L. J., Streng J. M., Leedom J. M. Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b. J Infect Dis. 1978 May;137 (Suppl):S180–S189. doi: 10.1093/infdis/137.supplement.s180. [DOI] [PubMed] [Google Scholar]
  34. Swabb E. A., Leitz M. A., Pilkiewicz F. G., Sugerman A. A. Pharmacokinetics of the monobactam SQ 26,776 after single intravenous doses in healthy subjects. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):131–140. doi: 10.1093/jac/8.suppl_e.131. [DOI] [PubMed] [Google Scholar]
  35. Sykes R. B., Bonner D. P., Bush K., Georgopapadakou N. H. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob Agents Chemother. 1982 Jan;21(1):85–92. doi: 10.1128/aac.21.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sykes R. B., Bonner D. P., Bush K., Georgopapadakou N. H., Wells J. S. Monobactams--monocyclic beta-lactam antibiotics produced by bacteria. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):1–16. doi: 10.1093/jac/8.suppl_e.1. [DOI] [PubMed] [Google Scholar]
  37. Sykes R. B., Cimarusti C. M., Bonner D. P., Bush K., Floyd D. M., Georgopapadakou N. H., Koster W. M., Liu W. C., Parker W. L., Principe P. A. Monocyclic beta-lactam antibiotics produced by bacteria. Nature. 1981 Jun 11;291(5815):489–491. doi: 10.1038/291489a0. [DOI] [PubMed] [Google Scholar]
  38. Winn H. R., Mendes M., Moore P., Wheeler C., Rodeheaver G. Production of experimental brain abscess in the rat. J Neurosurg. 1979 Nov;51(5):685–690. doi: 10.3171/jns.1979.51.5.0685. [DOI] [PubMed] [Google Scholar]
  39. Wise R., Andrews J. M., Hancox J. SQ 26,776, a novel beta-lactam: an in-vitro comparison with other antimicrobial agents. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):39–47. doi: 10.1093/jac/8.suppl_e.39. [DOI] [PubMed] [Google Scholar]
  40. Yu P. K., Washington J. A., 2nd Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae. Antimicrob Agents Chemother. 1981 Jul;20(1):63–65. doi: 10.1128/aac.20.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. de Louvois J., Gortavai P., Hurley R. Bacteriology of abscesses of the central nervous system: a multicentre prospective study. Br Med J. 1977 Oct 15;2(6093):981–984. doi: 10.1136/bmj.2.6093.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. de Louvois J., Gortvai P., Hurley R. Antibiotic treatment of abscesses of the central nervous system. Br Med J. 1977 Oct 15;2(6093):985–987. doi: 10.1136/bmj.2.6093.985. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES