Penetration of daptomycin into bone and synovial fluid in joint replacement.

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

Emergence of extensive-drug-resistant Pseudomonas aeruginosa in a French university hospital.

The aim of this study was to describe the molecular epidemiology and the mechanisms of resistance to beta-lactams of emerging extensive-drug-resistant Pseudomonas aeruginosa (XDRPA) in a tertiary-care university hospital over a three-year period. Analysis included antimicrobial susceptibility profiling and pulsed-field gel electrophoresis (PFGE). Resistance mechanisms to beta-lactams were identified: production of naturally occurring and acquired beta-lactamases, overproduction of MexAB-OprM and MexXY efflux systems and loss of porin OprD were assessed. Eighteen patients were colonised or infected with XDRPA which remained susceptible to colistin and, to a lesser extent, to rifampicin. beta-lactam resistance was, in most cases, due to the overproduction of AmpC, overproduction of the MexXY efflux system and loss of porin OprD. One isolate produced the class D extended-spectrum oxacillinase (OXA-ESBL) Oxa-28, but none produced metallo-beta-lactamase (MBL) or class A extended-spectrum beta-lactamase (ESBL). The XDRPA clustered in eight PFGE patterns and both the acquisition and loss of resistance determinants was observed within a single clone during its spread. The emergence of XDRPA isolates in our university hospital has been characterised by genotypic heterogeneity, variation of mechanisms of resistance to beta-lactams in a single clone and the predominance of chromosomally encoded resistance mechanisms.