Abstract
We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin.
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Selected References
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- Barakett V., Lesage D., Delisle F., Burghoffer B., Richard G., Vergez P., Petit J. C. Synergy of cefotaxime and fosfomycin against penicillin-resistant pneumococci. J Antimicrob Chemother. 1993 Jan;31(1):105–109. doi: 10.1093/jac/31.1.105. [DOI] [PubMed] [Google Scholar]
- Barakett V., Lesage D., Delisle F., Vergez P., Petit J. C. Killing kinetics of vancomycin and rifampin tested alone and in combination against penicillin-resistant Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis. 1993 Jan;12(1):69–71. doi: 10.1007/BF01997066. [DOI] [PubMed] [Google Scholar]
- Bingen E., Lambert-Zechovsky N., Mariani-Kurkdjian P., Doit C., Aujard Y., Fournerie F., Mathieu H. Bacterial counts in cerebrospinal fluid of children with meningitis. Eur J Clin Microbiol Infect Dis. 1990 Apr;9(4):278–281. doi: 10.1007/BF01968060. [DOI] [PubMed] [Google Scholar]
- 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]
- Cantón E. Cefotaxime breakpoint for Streptococcus pneumoniae. Antimicrob Agents Chemother. 1993 Mar;37(3):616–617. doi: 10.1128/aac.37.3.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Decazes J. M., Ernst J. D., Sande M. A. Correlation of in vitro time-kill curves and kinetics of bacterial killing in cerebrospinal fluid during ceftriaxone therapy of experimental Escherichia coli meningitis. Antimicrob Agents Chemother. 1983 Oct;24(4):463–467. doi: 10.1128/aac.24.4.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ernst J. D., Decazes J. M., Sande M. A. Experimental pneumococcal meningitis: role of leukocytes in pathogenesis. Infect Immun. 1983 Jul;41(1):275–279. doi: 10.1128/iai.41.1.275-279.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Gump D. W. Vancomycin for treatment of bacterial meningitis. Rev Infect Dis. 1981 Nov-Dec;3 Suppl:S289–S292. [PubMed] [Google Scholar]
- Haynes J., Hawkey P. M., Williams E. W. The in-vitro activity of combinations of penicillin and gentamicin against penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. J Antimicrob Chemother. 1986 Sep;18(3):426–428. doi: 10.1093/jac/18.3.426. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Latif R., Dajani A. S. Ceftriaxone diffusion into cerebrospinal fluid of children with meningitis. Antimicrob Agents Chemother. 1983 Jan;23(1):46–48. doi: 10.1128/aac.23.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lebel M. H., McCracken G. H., Jr Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. Pediatrics. 1989 Feb;83(2):161–167. [PubMed] [Google Scholar]
- Liñares J., Perez J. L., Garau J., Murgui L., Martín R. Comparative susceptibilities of penicillin-resistant pneumococci to co-trimoxazole, vancomycin, rifampicin and fourteen beta-lactam antibiotics. J Antimicrob Chemother. 1984 Apr;13(4):353–359. doi: 10.1093/jac/13.4.353. [DOI] [PubMed] [Google Scholar]
- Mason E. O., Jr, Kaplan S. L., Lamberth L. B., Tillman J. Increased rate of isolation of penicillin-resistant Streptococcus pneumoniae in a children's hospital and in vitro susceptibilities to antibiotics of potential therapeutic use. Antimicrob Agents Chemother. 1992 Aug;36(8):1703–1707. doi: 10.1128/aac.36.8.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCracken G. H., Jr, Chrane D. F., Thomas M. L. Pharmacologic evaluation of gentamicin in newborn infants. J Infect Dis. 1971 Dec;124 (Suppl):S214–23. doi: 10.1093/infdis/124.supplement_1.s214. [DOI] [PubMed] [Google Scholar]
- 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]
- Modai J., Vittecoq D., Decazes J. M., Meulemans A. Penetration of imipenem and cilastatin into cerebrospinal fluid of patients with bacterial meningitis. J Antimicrob Chemother. 1985 Dec;16(6):751–755. doi: 10.1093/jac/16.6.751. [DOI] [PubMed] [Google Scholar]
- Moellering R. C., Jr, Murray B. E., Schoenbaum S. C., Adler J., Wennersten C. B. A novel mechanism of resistance to penicillin-gentamicin synergism in Streptococcus faecalis. J Infect Dis. 1980 Jan;141(1):81–86. doi: 10.1093/infdis/141.1.81. [DOI] [PubMed] [Google Scholar]
- Nahata M. C., Fan-Havard P., Barson W. J., Bartkowski H. M., Kosnik E. J. Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements. Eur J Clin Pharmacol. 1990;38(5):515–517. doi: 10.1007/BF02336694. [DOI] [PubMed] [Google Scholar]
- 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]
- Stahl J. P., Croize J., Baud A., Bru J. P., de Rougemont P., Le Noc P., Micoud M. Traitement des méningites bactériennes neurochirurgicales par l'association ceftriaxone-fosfomycine. Pathol Biol (Paris) 1986 May;34(5):479–482. [PubMed] [Google Scholar]
- Tounian P., Girardet J. P., Josset P., Pauliat S., Boccon-Gibod L., Fontaine J. L. Intolérance aux hydrolysats de protéines du lait de vache à manifestations digestives. Arch Fr Pediatr. 1992 Aug-Sep;49(7):665–666. [PubMed] [Google Scholar]
- 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]
- Viladrich P. F., Gudiol F., Liñares J., Rufi G., Ariza J., Pallares R. Characteristics and antibiotic therapy of adult meningitis due to penicillin-resistant pneumococci. Am J Med. 1988 May;84(5):839–846. doi: 10.1016/0002-9343(88)90061-7. [DOI] [PubMed] [Google Scholar]
- Weingarten R. D., Markiewicz Z., Gilbert D. N. Meningitis due to penicillin-resistant Streptococcus pneumoniae in adults. Rev Infect Dis. 1990 Jan-Feb;12(1):118–124. doi: 10.1093/clinids/12.1.118. [DOI] [PubMed] [Google Scholar]
- Wong V. K., Wright H. T., Jr, Ross L. A., Mason W. H., Inderlied C. B., Kim K. S. Imipenem/cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J. 1991 Feb;10(2):122–125. doi: 10.1097/00006454-199102000-00009. [DOI] [PubMed] [Google Scholar]
- Yourassowsky E., Van der Linden M. P., Crokaert F., Glupczynski Y. Effect of antibiotics carry-over on bacterial counting by 'spiral plating'. J Antimicrob Chemother. 1988 Jan;21(1):138–140. doi: 10.1093/jac/21.1.138. [DOI] [PubMed] [Google Scholar]