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. 1997 Sep;41(9):1888–1891. doi: 10.1128/aac.41.9.1888

Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime.

I R Friedland 1, K P Klugman 1
PMCID: PMC164030  PMID: 9303379

Abstract

We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy. The median peak cerebrospinal fluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 microg/ml, respectively. In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinal fluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 microg/ml), and -resistant (MIC, 4 microg/ml) strains, respectively. High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.

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Selected References

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  1. Asmar B. I., Thirumoorthi M. C., Buckley J. A., Kobos D. M., Dajani A. S. Cefotaxime diffusion into cerebrospinal fluid of children with meningitis. Antimicrob Agents Chemother. 1985 Jul;28(1):138–140. doi: 10.1128/aac.28.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cabellos C., Martinez-Lacasa J., Martos A., Tubau F., Fernández A., Viladrich P. F., Gudiol F. Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis. Antimicrob Agents Chemother. 1995 Sep;39(9):2158–2160. doi: 10.1128/aac.39.9.2158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cherubin C. E., Eng R. H., Norrby R., Modai J., Humbert G., Overturf G. Penetration of newer cephalosporins into cerebrospinal fluid. Rev Infect Dis. 1989 Jul-Aug;11(4):526–548. doi: 10.1093/clinids/11.4.526. [DOI] [PubMed] [Google Scholar]
  4. Doern G. V., Brueggemann A., Holley H. P., Jr, Rauch A. M. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study. Antimicrob Agents Chemother. 1996 May;40(5):1208–1213. doi: 10.1128/aac.40.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Friedland I. R., McCracken G. H., Jr Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. N Engl J Med. 1994 Aug 11;331(6):377–382. doi: 10.1056/NEJM199408113310607. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Friedland I. R., Paris M., Shelton S., McCracken G. H. Time-kill studies of antibiotic combinations against penicillin-resistant and -susceptible Streptococcus pneumoniae. J Antimicrob Chemother. 1994 Aug;34(2):231–237. doi: 10.1093/jac/34.2.231. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Gaillard J. L., Abadie V., Cheron G., Lacaille F., Mahut B., Silly C., Matha V., Coustere C., Lokiec F. Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy. Antimicrob Agents Chemother. 1994 May;38(5):1209–1210. doi: 10.1128/aac.38.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Guibert M., Chahime H., Petit J., Odièvre M., Labrune P. Failure of cefotaxime treatment in two children with meningitis caused by highly penicillin-resistant Streptococcus pneumoniae. Acta Paediatr. 1995 Jul;84(7):831–833. doi: 10.1111/j.1651-2227.1995.tb13771.x. [DOI] [PubMed] [Google Scholar]
  11. Jacobs R. F., Kaplan S. L., Schutze G. E., Dajani A. S., Leggiadro R. J., Rim C. S., Puri S. K. Relationship of MICs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections. Antimicrob Agents Chemother. 1996 Apr;40(4):895–898. doi: 10.1128/aac.40.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. John C. C. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis. 1994 Feb;18(2):188–193. doi: 10.1093/clinids/18.2.188. [DOI] [PubMed] [Google Scholar]
  13. Klugman K. P., Friedland I. R., Bradley J. S. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother. 1995 Sep;39(9):1988–1992. doi: 10.1128/aac.39.9.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lecaillon J. B., Rouan M. C., Souppart C., Febvre N., Juge F. Determination of cefsulodin, cefotiam, cephalexin, cefotaxime, desacetyl-cefotaxime, cefuroxime and cefroxadin in plasma and urine by high-performance liquid chromatography. J Chromatogr. 1982 Mar 12;228:257–267. doi: 10.1016/s0378-4347(00)80438-7. [DOI] [PubMed] [Google Scholar]
  15. Lonks J. R., Durkin M. R., Meyerhoff A. N., Medeiros A. A. Meningitis due to ceftriaxone-resistant Streptococcus pneumoniae. N Engl J Med. 1995 Mar 30;332(13):893–894. doi: 10.1056/NEJM199503303321317. [DOI] [PubMed] [Google Scholar]
  16. París M. M., Hickey S. M., Uscher M. I., Shelton S., Olsen K. D., McCracken G. H., Jr Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother. 1994 Jun;38(6):1320–1324. doi: 10.1128/aac.38.6.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raymond J., Bingen E., Doit C., Brahimi N., Bergeret M., Badoual J., Gendrel D. Failure of cefotaxime treatment in a patient with penicillin-resistant pneumococcal meningitis and confirmation of nosocomial spread by random amplified polymorphic DNA analysis. Clin Infect Dis. 1995 Jul;21(1):234–235. doi: 10.1093/clinids/21.1.234. [DOI] [PubMed] [Google Scholar]
  18. Tan T. Q., Schutze G. E., Mason E. O., Jr, Kaplan S. L. Antibiotic therapy and acute outcome of meningitis due to Streptococcus pneumoniae considered intermediately susceptible to broad-spectrum cephalosporins. Antimicrob Agents Chemother. 1994 May;38(5):918–923. doi: 10.1128/aac.38.5.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Trang J. M., Jacobs R. F., Kearns G. L., Brown A. L., Wells T. G., Underwood F. L., Kluza R. B. Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis. Antimicrob Agents Chemother. 1985 Dec;28(6):791–795. doi: 10.1128/aac.28.6.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Viladrich P. F., Cabellos C., Pallares R., Tubau F., Martínez-Lacasa J., Liñares J., Gudiol F. High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins. Antimicrob Agents Chemother. 1996 Jan;40(1):218–220. doi: 10.1128/aac.40.1.218. [DOI] [PMC free article] [PubMed] [Google Scholar]

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