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

The Journal of Antimicrobial Chemotherapy
S RibesFrancesc Gudiol

Abstract

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). 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. 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 ag...Continue Reading

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Citations

Jul 23, 2009·The Journal of Antimicrobial Chemotherapy·Robert SauermannMarkus Zeitlinger
Jun 15, 2010·The Journal of Antimicrobial Chemotherapy·Ronny BeerBettina Pfausler
Jan 20, 2012·The Journal of Antimicrobial Chemotherapy·Hung-Jen TangYin-Ching Chuang
Oct 16, 2008·Clinical Microbiology Reviews·Damiana ChiavoliniSusanna Ricci
Jan 3, 2012·Research in Microbiology·Richard SchwameisRobert Sauermann
May 12, 2009·Médecine et maladies infectieuses·P Chavanet
Jul 22, 2008·Journal of Veterinary Pharmacology and Therapeutics·D H ZozayaL H Sumano
Jul 26, 2015·The Journal of Antimicrobial Chemotherapy·Clare C WalshPhillip J Bergen
Sep 29, 2011·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Argyris S MichalopoulosVassilios Gougoutas
Oct 14, 2017·The Journal of Antimicrobial Chemotherapy·Fiona FransenJohan W Mouton
Jan 21, 2010·Journal of Separation Science·Brompoj Prutthiwanasan, Leena Suntornsuk
Jan 16, 2007·Chemical Communications : Chem Comm·Ryan D WoodyerWilfred A van der Donk
Jul 8, 2017·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·M KussmannG Reznicek

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