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 g once on day ؊1) or therapy (1 g/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.

Granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, and other immunomodulatory therapies for the treatment of infectious diseases in solid organ transplant recipients

“…G-CSF increased mortality in murine models of pneumonia due to Klebsiella pneumoniae or E. coli and produced variable results in other animal models depending on the class of antibiotic coadministered [16][17][18][19]. Taken together, these results demonstrated the potential for harm, as well as benefit, from G-CSF therapy.…”

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections

“…7–11 It is active against non-growing Escherichia coli and Bacteroides fragilis in experimental abscesses, 12 and its in vitro activity against S. aureus and E. coli is not reduced in an anaerobic milieu. 13 It is not, however, recommended against methicillin-resistant S. aureus (MRSA).…”

“…Moxifloxacin has an extended spectrum of activity against Gram-positive cocci, including methicillin-susceptible Staphylococcus aureus , and aerobic and anaerobic bacteria, and significant activity against many Gram-negative bacteria. 7 – 11 It is active against non-growing Escherichia coli and Bacteroides fragilis in experimental abscesses, 12 and its in vitro activity against S. aureus and E. coli is not reduced in an anaerobic milieu. 13 It is not, however, recommended against methicillin-resistant S. aureus (MRSA).…”