High activity of Fosfomycin and Rifampin against methicillin-resistant staphylococcus aureus biofilm in vitro and in an experimental foreign-body infection model.

Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 µg/ml; daptomycin, 0.125 µg/ml; vancomycin, 1 µg/ml; rifampin, 0.04 µg/ml; and tigecycline, 0.125 µg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log10 CFU/ml at 128 × the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by <1 log10 CFU/ml with fosfomycin and tigecycline, 1.7 log10 with daptomycin, 2.2 log10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log10 with fosfomycin-daptomycin, and >6.0 log10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cage-associated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 µg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cage-associated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-associated infections, but it cannot replace rifampin as an antibiofilm agent.

Treatment of subtrochanteric nonunions.

The purpose of this retrospective study was to evaluate our results of treating subtrochanteric nonunions with a (AO/ASIF) blade plate. We treated a total of 32 patients (33 hips) with a subtrochanteric nonunion with a blade plate. Outcome measures were time to healing, complications after the index-operation and the Merle d'Aubigne hip score at follow-up. Union was achieved in 32 of the 33 hips after an average of 5 months. Complications were seen in nine patients (nine hips); five complications required re-intervention and four minor complications were treated conservatively. According to the Merle d'Aubigne hip score, 10 patients were rated as excellent, 15 as good and 7 as fair. This study shows that treatment of a subtrochanteric nonunion with a blade plate consistently leads to bony union with a good to excellent hip score in the vast majority of the patients (25 out of 33 hips).