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Efficacy of fosfomycin alone or combined with imipenem, linezolid and vancomycin, in vitro and in a murine peritonitis model due to two strains of GISA

Abstract number: P1908

Pachon-Ibañez M., Ribes S., Cabellos C., Dominguez M., Murillo O., Cardiel M., Tubau F., Ariza J., Gudiol F.

Objectives: To study the efficacy of Fosfomycin (FOM) and its combinations with Imipenem (IMP), Vancomycin (VAN) and Linezolid (LZD) in infections due to GISA strains.

Methods: MICs (mg/l) of the Staphylococcus aureus strains were: strain A (FOM 4, IMP 32, VAN 4, LZD 1, CLO 1024) and B (FOM 1024, IMP 64, VAN 8, LZD 2, CLO 1024). In vitro time-killing curves were performed over 24 h to test bactericidal effect of FOM, IMP, VAN and LZD and synergy. In vivo studies: Peritonitis in C57BL/6 mice was induced by intraperitoneal inoculation of 108 CFU/ml. Four hours later (0 h), mice were sorted in Control (not treated), FOM (100 mg/kg/5 h), IMP (30 mg/kg/5 h), VAN (60 mg/kg/5 h), LZD (35 mg/kg/5 h) and FOM+IMP, FOM+VAN, FOM+LZD, receiving sc therapy over 25 h. At 0 and 25 h, a blood sample was taken to assess bacteraemia rates and peritoneal wash was performed to determine bacterial counts in peritoneal fluid. Mortality was analysed at 25 h.

Bacterial decrease (D log cfu/ml) and bacteraemia rates (Br) at 25 h

Results: In vitro, the combination of FOM (Cmax and 1×MIC) plus IMP (1×MIC) were bactericidal and synergistic for strain A. In the animal model at 25 h, for strain A, all therapies were more effective than controls and FOM+IMP and FOM+LZD were significantly better than VAN (p < 0.05). For strain B, all treatment groups except IMP were better than controls and FOM+VAN was significantly better than IMP. Bacterial decrease and bacteraemia rates of the different groups are shown in the table.

Mortality in controls was 90% and 100% with strain A and B, respectively, all therapy groups were better than controls except IMP for strain B (p < 0.05).

Conclusions: Combinations of FOM were effective in the treatment of infections caused by the hGISA strain. In the treatment of infection caused by the GISA strain only the combination FOM plus VAN was effective.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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