minocycline and Foreign-Bodies

Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC(log)) and stationary phase (MBC(stat)) were 0.12, 0.12, and 8 μg/ml for fosfomycin, 0.25, 32, and 32 μg/ml for tigecycline, 0.25, 0.5, and 2 μg/ml for colistin, and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log(10) CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log(10) CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Biofilms; Colistin; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Foreign Bodies; Fosfomycin; Gentamicins; Guinea Pigs; Male; Microbial Sensitivity Tests; Minocycline; Polytetrafluoroethylene; Prostheses and Implants; Tigecycline

Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA.. A tissue-cage infection model were used; therapy with tigecycline, vancomycin, rifampin, tigecycline plus rifampin and vancomycin plus rifampin was administered intraperitoneally for 7 days. The antibiotic efficacy was evaluated in the tissue-cage fluid and in the coverslips (attached bacteria); the emergence of resistance was screened.. Among monotherapies rifampin was the best treatment (decrease in log CFU/ml of tissue-cage fluid, 2.75) (P < 0.05). The addition of rifampin improved the efficacy of vancomycin (decrease, 2.28) and tigecycline (decrease, 1.56) in solitary; there were not significantly differences between tigecycline-rifampin (decrease, 3.39) and vancomycin-rifampin (decrease, 3.70), but only the latter was better than rifampin alone (P < 0.05). Resistant strains were only detected using rifampin alone.. tigecycline alone was the least effective treatment. Tigecycline-rifampin prevented the emergence of rifampin resistance, thus allowing the benefits of rifampin over time against staphylococcal foreign-body infections, but its efficacy needs to be evaluated in comparison with other anti-MRSA combined therapies.

Topics: Animals; Anti-Bacterial Agents; Diffusion Chambers, Culture; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Foreign Bodies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Models, Animal; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Time Factors; Treatment Outcome; Vancomycin

Twice-daily 7-day regimens of tigecycline (7 mg/kg) and vancomycin (50 mg/kg) were compared in a rat tissue cage model of chronic foreign-body infection due to methicillin (meticillin)-resistant Staphylococcus aureus strain MRGR3. Subcutaneously administered tigecycline reached levels in tissue cage fluid that were nearly equivalent or slightly superior to the antibiotic MIC (0.5 microg/ml) for strain MRGR3. After 7 days, equivalent, significant reductions in bacterial counts were recorded for tigecycline-treated and vancomycin-treated rats, compared with those for untreated animals.

Topics: Animals; Anti-Bacterial Agents; Foreign Bodies; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rats; Staphylococcal Infections; Tigecycline; Vancomycin