Effect of recombinant murine granulocyte colony-stimulating factor with or without fluoroquinolone therapy on mixed-infection abscesses in mice.

Abstract

The aim of the study was to determine if immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (G-CSF) improves the efficacy of trovafloxacin or moxifloxacin in abscesses containing Bacillus fragilis ATCC 23745 and different Escherichia coli strains varying in virulence. Treatment of mice inoculated with 10(7) CFU B. fragilis and 10(5) CFU low-virulence E. coli with either trovafloxacin (150 mg/kg/day every 24 hours, days 3 to 7) or moxifloxacin (96 mg/kg/day every 12 hours, days 3 to 7), significantly reduced the number of B. fragilis to 6.9 +/- 0.35 and 5.8 +/- 0.10 and that of E. coli to 4.9 +/- 0.09 and 4.2 +/- 0.07 log CFU/abscess for trovafloxacin and moxifloxacin, respectively, compared to controls (B. fragilis 8.7 and E. coli 7.4 log CFU/abscess) on day 8. Also, moxifloxacin was more potent than trovafloxacin. Addition of G-CSF prophylaxis (1 mug once on day -1) or therapy (1 mug/day on days 3 to 7) to fluoroquinolone treatment did not improve the efficacy of fluoroquinolone therapy alone. The effect of moxifloxacin with or without G-CSF prophylaxis on abscesses with a virulent hemolytic E. coli strain was also studied. In moxifloxacin-treated mice, 75% survived infection compared to 10% of controls. Combining moxifloxacin with G-CSF prophylaxis significantly decreased survival (30%) compared to moxifloxacin alone. In addition, G-CSF prophylaxis resulted in a threefold (E. coli) to 100-fold (B. fragilis) increased outgrowth in the abscesses of surviving mice. In conclusion, the addition of G-CSF to a fluoroquinolone is not advisable since, depending on the virulence of the E. coli strains, this might detrimentally influence the outcome of therapy.

• Authors: Lorna E T Stearne, Alieke G Vonk, Bart Jan Kullberg, Inge C Gyssens
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 9 Pg. 3668-75 (Sep 2005) ISSN: 0066-4804 [Print] United States
• PMID: 16127038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Aza Compounds
• Cytokines
• Fluoroquinolones
• Quinolines
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Moxifloxacin

Topics

• Abscess (drug therapy, microbiology)
• Animals
• Anti-Infective Agents (pharmacology, therapeutic use)
• Aza Compounds (pharmacology, therapeutic use)
• Bacillus (pathogenicity)
• Colony Count, Microbial
• Cytokines (metabolism)
• Escherichia coli (pathogenicity)
• Female
• Fluoroquinolones (pharmacology, therapeutic use)
• Granulocyte Colony-Stimulating Factor (pharmacology, therapeutic use)
• Mice
• Mice, Inbred BALB C
• Microbial Sensitivity Tests
• Moxifloxacin
• Quinolines (pharmacology, therapeutic use)
• Recombinant Proteins
• Spleen (microbiology)
• Survival Analysis
• Treatment Outcome