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Antimicrobial Agents and Chemotherapy, September 2005, p. 3668-3675, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3668-3675.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effect of Recombinant Murine Granulocyte Colony-Stimulating Factor with or without Fluoroquinolone Therapy on Mixed-Infection Abscesses in Mice

Lorna E. T. Stearne,1,{dagger} Alieke G. Vonk,3,4 Bart Jan Kullberg,3 and Inge C. Gyssens1,2*

Department of Medical Microbiology & Infectious Diseases,1 Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam,2 Department of Medicine, Division of General Internal Medicine, University Medical Center Nijmegen, and Nijmegen University Center for Infectious Diseases, Nijmegen,3 Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands4

Received 3 January 2005/ Returned for modification 22 March 2005/ Accepted 18 June 2005

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 107 CFU B. fragilis and 105 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 µg once on day –1) or therapy (1 µg/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.

* Corresponding author. Mailing address: Department of Medical Microbiology & Infectious Diseases, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Phone: 31-10-463 4406. Fax: 31-10-463 3875. E-mail: i.gyssens{at}erasmusmc.nl.

{dagger} Present address: Department for Environment, Food & Rural Affairs, Animal Health and Welfare Veterinary Research Division, Room 505, Cromwell House, Dean Stanley Street, Westminster, London SW1P 3JH, United Kingdom.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3668-3675, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3668-3675.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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