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. 1994 Jun;38(6):1320–1324. doi: 10.1128/aac.38.6.1320

Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

M M París 1, S M Hickey 1, M I Uscher 1, S Shelton 1, K D Olsen 1, G H McCracken Jr 1
PMCID: PMC188205  PMID: 8092832

Abstract

Treatment of pneumococcal meningitis has become problematic because of the emergence of penicillin- and cephalosporin-resistant strains and because of the concern that dexamethasone therapy might reduce penetration of antibiotics into the cerebrospinal fluid (CSF). We addressed these issues with our rabbit meningitis model by studying two pneumococcal isolates that were resistant to penicillin and ceftriaxone and susceptible to vancomycin and rifampin. Ceftriaxone, vancomycin, and rifampin were given alone or in combination, with or without coadministration of dexamethasone. Treatment was started 12 to 14 h after intracisternal inoculation of approximately 10(4) CFU of one of the organisms. Rifampin concentrations in serum and CSF were similar, regardless of whether dexamethasone was given, whereas those of ceftriaxone were somewhat lower at each time point in animals given dexamethasone. The penetration of vancomycin into CSF was consistently and substantially reduced with dexamethasone treatment, which resulted in a delay in CSF sterilization not observed in non-dexamethasone-treated animals. When rifampin was used with ceftriaxone for treatment of meningitis caused by the more resistant strain, bacteriologic cure occurred promptly, with or without dexamethasone therapy. In areas with high rates of occurrence of resistant pneumococcal strains, we believe initial empiric therapy of bacterial meningitis should include two antibiotics: ceftriaxone and either rifampin or vancomycin. When dexamethasone is used, the combination of ceftriaxone and rifampin is preferred for therapy.

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Selected References

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  1. Adams W. G., Deaver K. A., Cochi S. L., Plikaytis B. D., Zell E. R., Broome C. V., Wenger J. D. Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA. 1993 Jan 13;269(2):221–226. [PubMed] [Google Scholar]
  2. Alonso J., Madrigal V., García-Fuentes M. Recurrent meningitis from a multiply resistant Streptococcus pneumoniae strain treated with erythromycin. Pediatr Infect Dis J. 1991 Mar;10(3):256–256. doi: 10.1097/00006454-199103000-00022. [DOI] [PubMed] [Google Scholar]
  3. Asensi F., Pérez-Tamarit D., Otero M. C., Gallego M., Llanes S., Abadia C., Cantó E. Imipenem-cilastatin therapy in a child with meningitis caused by a multiply resistant pneumococcus. Pediatr Infect Dis J. 1989 Dec;8(12):895–895. doi: 10.1097/00006454-198912000-00019. [DOI] [PubMed] [Google Scholar]
  4. Black S. B., Shinefield H. R. Immunization with oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine on a large health maintenance organization population: extended follow-up and impact on Haemophilus influenzae disease epidemiology. The Kaiser Permanente Pediatric Vaccine Study Group. Pediatr Infect Dis J. 1992 Aug;11(8):610–613. [PubMed] [Google Scholar]
  5. Bradley J. S., Connor J. D. Ceftriaxone failure in meningitis caused by Streptococcus pneumoniae with reduced susceptibility to beta-lactam antibiotics. Pediatr Infect Dis J. 1991 Nov;10(11):871–873. [PubMed] [Google Scholar]
  6. Broadhurst L. E., Erickson R. L., Kelley P. W. Decreases in invasive Haemophilus influenzae diseases in US Army children, 1984 through 1991. JAMA. 1993 Jan 13;269(2):227–231. [PubMed] [Google Scholar]
  7. Caputo G. M., Appelbaum P. C., Liu H. H. Infections due to penicillin-resistant pneumococci. Clinical, epidemiologic, and microbiologic features. Arch Intern Med. 1993 Jun 14;153(11):1301–1310. [PubMed] [Google Scholar]
  8. Chesney P. J. The escalating problem of antimicrobial resistance in Streptococcus pneumoniae. Am J Dis Child. 1992 Aug;146(8):912–916. doi: 10.1001/archpedi.1992.02160200034022. [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. Friedland I. R., Istre G. R. Management of penicillin-resistant pneumococcal infections. Pediatr Infect Dis J. 1992 Jun;11(6):433–435. doi: 10.1097/00006454-199206000-00002. [DOI] [PubMed] [Google Scholar]
  11. Friedland I. R., Paris M., Ehrett S., Hickey S., Olsen K., McCracken G. H., Jr Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother. 1993 Aug;37(8):1630–1636. doi: 10.1128/aac.37.8.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friedland I. R., Shelton S., Paris M., Rinderknecht S., Ehrett S., Krisher K., McCracken G. H., Jr Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J. 1993 Mar;12(3):196–200. doi: 10.1097/00006454-199303000-00004. [DOI] [PubMed] [Google Scholar]
  13. Friedland I. R. Therapy of penicillin- and cephalosporin-resistant pneumococcal infections. Ann Med. 1993 Oct;25(5):451–455. doi: 10.3109/07853899309147311. [DOI] [PubMed] [Google Scholar]
  14. Girgis N. I., Farid Z., Mikhail I. A., Farrag I., Sultan Y., Kilpatrick M. E. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J. 1989 Dec;8(12):848–851. doi: 10.1097/00006454-198912000-00004. [DOI] [PubMed] [Google Scholar]
  15. Jackson M. A., Shelton S., Nelson J. D., McCracken G. H., Jr Relatively penicillin-resistant pneumococcal infections in pediatric patients. Pediatr Infect Dis. 1984 Mar-Apr;3(2):129–132. doi: 10.1097/00006454-198403000-00010. [DOI] [PubMed] [Google Scholar]
  16. Jafari H. S., Sáez-Llorens X., Ramilo O., Shelton S. L., McCracken G. H., Jr Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis. Antimicrob Agents Chemother. 1991 Feb;35(2):220–223. doi: 10.1128/aac.35.2.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kennedy W. A., Hoyt M. J., McCracken G. H., Jr The role of corticosteroid therapy in children with pneumococcal meningitis. Am J Dis Child. 1991 Dec;145(12):1374–1378. doi: 10.1001/archpedi.1991.02160120042016. [DOI] [PubMed] [Google Scholar]
  18. Lebel M. H., Freij B. J., Syrogiannopoulos G. A., Chrane D. F., Hoyt M. J., Stewart S. M., Kennard B. D., Olsen K. D., McCracken G. H., Jr Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. N Engl J Med. 1988 Oct 13;319(15):964–971. doi: 10.1056/NEJM198810133191502. [DOI] [PubMed] [Google Scholar]
  19. Lebel M. H., Hoyt M. J., Waagner D. C., Rollins N. K., Finitzo T., McCracken G. H., Jr Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis. Am J Dis Child. 1989 Mar;143(3):301–306. doi: 10.1001/archpedi.1989.02150150055017. [DOI] [PubMed] [Google Scholar]
  20. McCracken G. H., Jr, Sakata Y. Antimicrobial therapy of experimental meningitis caused by Streptococcus pneumoniae strains with different susceptibilities to penicillin. Antimicrob Agents Chemother. 1985 Feb;27(2):141–145. doi: 10.1128/aac.27.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moellering R. C., Jr, Krogstad D. J., Greenblatt D. J. Pharmacokinetics of vancomycin in normal subjects and in patients with reduced renal function. Rev Infect Dis. 1981 Nov-Dec;3 Suppl:S230–S235. [PubMed] [Google Scholar]
  22. Murphy T. V., White K. E., Pastor P., Gabriel L., Medley F., Granoff D. M., Osterholm M. T. Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination. JAMA. 1993 Jan 13;269(2):246–248. [PubMed] [Google Scholar]
  23. Mustafa M. M., Ramilo O., Mertsola J., Risser R. C., Beutler B., Hansen E. J., McCracken G. H., Jr Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis. J Infect Dis. 1989 Nov;160(5):818–825. doi: 10.1093/infdis/160.5.818. [DOI] [PubMed] [Google Scholar]
  24. Odio C. M., Faingezicht I., Paris M., Nassar M., Baltodano A., Rogers J., Sáez-Llorens X., Olsen K. D., McCracken G. H., Jr The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med. 1991 May 30;324(22):1525–1531. doi: 10.1056/NEJM199105303242201. [DOI] [PubMed] [Google Scholar]
  25. Schaad U. B., Lips U., Gnehm H. E., Blumberg A., Heinzer I., Wedgwood J. Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group. Lancet. 1993 Aug 21;342(8869):457–461. doi: 10.1016/0140-6736(93)91592-a. [DOI] [PubMed] [Google Scholar]
  26. Shapiro E. P. Infections caused by Haemophilus influenzae type b. The beginning of the end? JAMA. 1993 Jan 13;269(2):264–266. [PubMed] [Google Scholar]
  27. Simon H. J., Yin E. J. Microbioassay of antimicrobial agents. Appl Microbiol. 1970 Apr;19(4):573–579. doi: 10.1128/am.19.4.573-579.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sloas M. M., Barrett F. F., Chesney P. J., English B. K., Hill B. C., Tenover F. C., Leggiadro R. J. Cephalosporin treatment failure in penicillin- and cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J. 1992 Aug;11(8):662–666. [PubMed] [Google Scholar]
  29. Syrogiannopoulos G. A., Hansen E. J., Erwin A. L., Munford R. S., Rutledge J., Reisch J. S., McCracken G. H., Jr Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation. J Infect Dis. 1988 Feb;157(2):237–244. doi: 10.1093/infdis/157.2.237. [DOI] [PubMed] [Google Scholar]
  30. Täuber M. G., Zak O., Scheld W. M., Hengstler B., Sande M. A. The postantibiotic effect in the treatment of experimental meningitis caused by Streptococcus pneumoniae in rabbits. J Infect Dis. 1984 Apr;149(4):575–583. doi: 10.1093/infdis/149.4.575. [DOI] [PubMed] [Google Scholar]
  31. Viladrich P. F., Gudiol F., Liñares J., Pallarés R., Sabaté I., Rufí G., Ariza J. Evaluation of vancomycin for therapy of adult pneumococcal meningitis. Antimicrob Agents Chemother. 1991 Dec;35(12):2467–2472. doi: 10.1128/aac.35.12.2467. [DOI] [PMC free article] [PubMed] [Google Scholar]

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