EFFECT OF COMBINATION THERAPY OF RIFAMPICIN AND AZITHROMYCIN ON TNF LEVELS DURING A RAT MODEL OF CHRONIC OSTEOMYELITIS

The purpose of the present study was to evaluate the combination of az ithromycin and rifampicin on experimental chronic osteomyelitis due to Staphylococcus aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor (TNF), a cytokine implicated in inflammation -induced bone pathology, and histopathological changes during infectio n and following antibiotic treatment were evaluated. Rats were infecte d with S. aureus by direct tibial inoculation and then randomized 56 d ays after infection to receive saline treatment or a combination of az ithromycin and rifampicin (50 mg/kg po and 25 mg/kg sc respectively) o nce daily for 21 days. The combination of azithromycin and rifampicin was successful as determined by dramatic reduction in bone bacterial c ounts (similar to log 4 cfu), but regrowth of the organisms occurred s uggesting that the duration of treatment was insufficient. TNF alpha m RNA and TNF activity were constantly elevated by approximately 20- and >200-fold, respectively, and remained elevated irrespective of antimi crobial treatment. Bone histology revealed extensive increase in bone turnover in both the infected and antibiotic treated bones with no dif ference being observed between the groups. This suggests that, in infe cted bone, the elevated TNF levels observed may be directly related to the bone pathology and both remain largely unchanged despite potent a ntibiotic therapy.