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Successful therapy of experimental chronic foreign-body infection due to methicillin-resistant Staphylococcus aureus by antimicrobial combinations

Herrmann, M.
Published in Antimicrobial agents and chemotherapy. 1991, vol. 35, no. 12, p. 2611-2616
Abstract We compared the efficacy of a long-duration (3-week) therapy of vancomycin, fleroxacin, fleroxacin plus rifampin, and vancomycin plus fleroxacin and rifampin in a recently developed rat model of chronic staphylococcal foreign-body infection. Subcutaneous tissue cages containing polymethylmethacrylate coverslips were infected with 1 x 10(5) to 5 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. Three weeks later, a quantitative culturing of the fluid that had accumulated in the cages was done (mean, 6.72 log10 CFU/ml; n = 110) and treatment was initiated after randomization. The CFUs in the cage fluid were counted on days 11 and 22 and 1 week after the termination of treatment; in addition, a final culture of coverslips (surface-bound microorganisms) was performed. The three-drug therapy was significantly superior to the other treatments on day 11 (a 5.16 log10 decrease of bacterial counts versus a 2.12 log10 to 2.94 log10 decrease for vancomycin, fleroxacin, and fleroxacin plus rifampin; P less than 0.01). On day 22, count decreases were 4.16 log10 for vancomycin, 4.91 log10 for fleroxacin (vancomycin versus fleroxacin, not significant), 6.14 log10 for two-drug therapy, and 6.34 log10 for three-drug therapy (vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin, not significant; fleroxacin-rifampin versus monotherapies, P less than 0.01); the numbers of CFU in most cage fluids were under the detection limit (20 CFU/ml) in combination groups. One week after the end of treatment, 92% of fluids and coverslips (detection limit, 1 CFU) were culture negative with tritherapy, 88% of fluids and 41% of coverslips were negative with bitherapy, and less than 12% of fluids and coverslips were negative with single drugs (for coverslips, P was <0.01 for vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin and P was <0.001 for fleroxacin-rifampin versus the monotherapies). No mutants resistant to rifampin or fleroxacin were detected. In conclusion, antimicrobial combinations were highly effective and superior to single drugs in treating a chronic staphylococcal foreign-body infection for 3 weeks. The three-drug therapy decreased bacterial counts more rapidly than the two-drug therapy under study and appeared to be curative in most cases.
Keywords AnimalsCells, CulturedChronic DiseaseDrug InteractionsDrug Therapy, CombinationFleroxacin/administration & dosage/ therapeutic useForeign-Body Reaction/ drug therapyMethicillin ResistanceMicrobial Sensitivity TestsRatsRats, Inbred StrainsRifampin/administration & dosage/ therapeutic useStaphylococcal Infections/ drug therapyStaphylococcus aureus/ drug effectsVancomycin/administration & dosage/ therapeutic use
PMID: 1810196
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Other version: http://aac.asm.org/cgi/reprint/35/12/2611.pdf
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CHUARD, Christian Robert et al. Successful therapy of experimental chronic foreign-body infection due to methicillin-resistant Staphylococcus aureus by antimicrobial combinations. In: Antimicrobial agents and chemotherapy, 1991, vol. 35, n° 12, p. 2611-2616. doi: 10.1128/aac.35.12.2611 https://archive-ouverte.unige.ch/unige:7143

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Deposited on : 2010-06-21

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