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Background  Increased antibiotic resistance against  Staphylococcus aureus  and low penetration into bone requires regimen optimization of available drugs.    Methods  We evaluate pharmoacokinetic and pharmacodynamic parameters (PK/PD) as well as  in vivo  interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient’s own serum directed against his own isolated  S. aureus  strain to reproduce  in vivo  conditions as closely as possible.    Results  The continuous flucloxacillin infusion constantly generated plasma free drug levels largely exceeding the serum minimal inhibitory concentrations (mean 74-fold). Combination with rifampicin significantly increased flucloxacillin levels by 44.5%. Such an increase following rifampicin introduction was documented in 10/15 patients, whereas a decrease was observed in 1/15 patients. Finally, all infections were cured and the combination was well tolerated.    Conclusions  In this  in vivo  methodological pilot study among adult patients with orthopaedic infections due to  S. aureus , we describe a new method and reveal substantial but inconsistent interactions between flucloxacillin and rifampicin, of which the clinical significance remains unclear.

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In vivo interactions of continuous flucloxacillin infusion and high-dose oral rifampicin in the serum of 15 patients with bone and soft tissue infections due to Staphylococcus aureus - a methodological and pilot study