There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI. A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).Aims
Methods
Calcium sulphate (CaSO4) is a resorbable material
that can be used simultaneously as filler of a dead space and as
a carrier for the local application of antibiotics. Our aim was
to describe the systemic exposure and the wound fluid concentrations
of vancomycin in patients treated with vancomycin-loaded CaSO4 as
an adjunct to the routine therapy of bone and joint infections. A total of 680 post-operative blood and 233 wound fluid samples
were available for analysis from 94 implantations performed in 87
patients for various infective indications. Up to 6 g of vancomycin
were used. Non-compartmental pharmacokinetic analysis was performed
on the data from 37 patients treated for an infection of the hip.Aims
Patients and Methods
Calcium sulphate is a resorbable void filler that can be used for local antibiotic delivery. Results from clinical studies on chronic osteomyelitis thus treated with local vancomycin have already been published. Despite significant exposure to this drug, there are no pharmacokinetic studies published so far. Based on observations in our patients, a model predicting vancomycin serum and wound fluid levels and toxicity potential is presented. Following implantation of Osteoset® added with vancomycin, serum and wound fluid concentrations of this antibiotic have been monitored systematically. The pharmacokinetic analysis was performed using a non-linear mixed-effects model based on a one-compartment model with first-degree absorption.Introduction
Methods
