dibekacin and Granuloma

Biofilms are a major concern for clinicians in the treatment of infectious disease because of the resistance to a wide range of antibiotics. Using a rat air pouch model, methicillin-resistant Staphylococcus aureus (MRSA) growing as a biofilm was treated with a combination of fosfomycin (FOM) and arbekacin (ABK) or by the agents alone. This model has the advantage of permitting frequent sampling of exudates for bacterial counts and anti-bacterial activity, and morphological examination of the biofilm structure and inflammatory process in the pouch tissues. A clear synergistic effect was observed in the rats treated with a combination of fosfomycin and arbekacin. Morphological studies using scanning electron microscopy and histological staining showed dramatic changes of the biofilm structure as well as the inflammatory response in the rats. These results suggested an enhancement of bactericidal activity of arbekacin penetrating through the biofilm layer by virtue of fosfomycin. A possible mechanism of the synergistic effect is discussed.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Biofilms; Dibekacin; Disease Models, Animal; Drug Synergism; Fosfomycin; Granuloma; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus

Biofilms are a major concern for clinicians in the treatment of infectious disease because of their resistance to a wide range of antibiotics. Arbekacin, an aminoglycoside antibiotic, is the drug of choice for the treatment of infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, it has not yet been defined whether arbekacin tends to penetrate into the biofilm structure induced by MRSA infection. In this study, we treated a biofilm mode of MRSA growth with arbekacin, using a rat air-pouch model. The model has the advantage of permitting frequent sampling of exudates for bacterial counts and antibacterial activity. A clear dose-dependent bactericidal effect was detected in rats treated with arbekacin at concentrations between 0.3 and 10 mg/kg, but 0.1 mg/kg of arbekacin was ineffective against the experimental MRSA infection in rats. Morphological studies using scanning electron microscopy and histochemical staining demonstrated that an effective dosage of arbekacin induced dramatic changes in the biofilm membranous structure as well as in the inflammatory response, resulting in eradication of the biofilm structure and resolution of inflammation.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Biofilms; Dibekacin; Disease Models, Animal; Granuloma; Humans; Male; Methicillin Resistance; Microscopy, Electron, Scanning; Necrosis; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome