JAC Advance Access originally published online on February 28, 2006
Journal of Antimicrobial Chemotherapy 2006 57(5):931-936; doi:10.1093/jac/dkl047
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evaluation of fosfomycin alone and in combination with ceftriaxone or vancomycin in an experimental model of meningitis caused by two strains of cephalosporin-resistant Streptococcus pneumoniae
1 Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL–Hospital Universitari de Bellvitge–Universitat de Barcelona, L'Hospitalet, Barcelona, Spain; 2 Microbiology Department, IDIBELL–Hospital Universitari de Bellvitge–Universitat de Barcelona, L'Hospitalet, Barcelona, Spain
Received 18 November 2005; returned 4 January 2006; revised 31 January 2006; accepted 2 February 2006
* Correspondence address. Infectious Diseases Service, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. Tel: +34-932607625/+34-934035805; Fax: +34-932607637; E-mail: sribes{at}ub.edu
Objectives: To study the in vitro and in vivo efficacy of fosfomycin, alone and in combination with ceftriaxone or vancomycin, against two strains of Streptococcus pneumoniae: HUB 2349 (fosfomycin and ceftriaxone, MICs 16 and 2 mg/L) and ATCC 51916 (MICs 4 and 32 mg/L).
Methods: Pharmacokinetics/pharmacodynamics data were collected from the study of eight infected animals after a single intravenous dose of 300 mg/kg of fosfomycin. Time–kill curves were plotted using CSF antibiotic concentrations achievable clinically. In the rabbit model, we studied the efficacy and effects on inflammation of treatment with fosfomycin 1200 mg/kg/day, ceftriaxone 100 mg/kg/day and vancomycin 30 mg/kg/day, over 26 h.
Results: Fosfomycin peak level in serum was 324.48 ± 102.1 mg/L at 0.5 h; CSF penetration was 49.2%. Time–kill curves showed that fosfomycin was bactericidal against the ATCC 51916 strain and that the addition of fosfomycin to ceftriaxone or vancomycin was synergic against the HUB 2349 strain. Resistance to fosfomycin was detected both when fosfomycin was studied alone and in combination. In the rabbit model, fosfomycin showed bactericidal activity only against the ATCC 51916 strain. Combinations of fosfomycin with ceftriaxone or vancomycin were bactericidal against both strains; they improved efficacy and decreased CSF inflammatory parameters over monotherapies, without showing statistical differences in comparison with the combination of ceftriaxone and vancomycin.
Conclusions: Fosfomycin in combination with ceftriaxone or vancomycin appeared to be effective for the treatment of experimental cephalosporin-resistant pneumococcal meningitis. These combinations are possible alternatives in cases of allergy or intolerance to first-line drugs or in rare meningitis caused by highly cephalosporin-resistant pneumococci.
Keywords: pneumococcal meningitis , cephalosporins , Streptococcus pneumoniae , resistance
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Sauermann, R. Schwameis, M. Fille, M. L. Camuz Ligios, and M. Zeitlinger Cerebrospinal fluid impairs antimicrobial activity of fosfomycin in vitro J. Antimicrob. Chemother., October 1, 2009; 64(4): 821 - 823. [Abstract] [Full Text] [PDF]
|
|