Abstract
BackgroundIncreased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs.MethodsWe 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.ResultsThe 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.ConclusionsIn 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.
Highlights
Staphylococcus aureus is one of the most prevalent pathogen in bone and soft-tissue infections associated with and without foreign material
For severe bone and soft tissue infections due to S. aureus, whether associated with orthopaedic implants or not, only limited data is currently available for flucloxacillin in continuous infusion alone (Howden and Richards 2001; Hackbarth et al 1986; Leder et al 1999) or in combination with rifampicin
Subjects and treatment Fifteen adult patients hospitalized for acute bone and soft tissue infections due to S. aureus were prospectively included in this methodological pilot study
Summary
Staphylococcus aureus is one of the most prevalent pathogen in bone and soft-tissue infections associated with and without foreign material. New pharmacokinetic and pharmacodynamic (PK/PD) studies in vivo are required to optimize the potency of today’s available antimicrobial regimens (Le and Bayer 2003; Czekaj et al 2011). In this methodological and pilot study, we prospectively investigate activity parameters of a combined oral rifampicin and continuous flucloxacillin regimen in 15 adult hospitalized patients. Speaking, we use the patient’s own serum directed against his own isolated S. aureus strain to reproduce in vivo conditions as closely as possible This method may be clinically more relevant than in vitro studies on synergism/antagonism. Increased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs
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