tedizolid-phosphate and Osteomyelitis

Tedizolid, a second-generation oxazolidinone that displays a potent activity against Gram-positive pathogens, could be an interesting option for the treatment of bone and joint infections (BJIs). The aim of the study was to determine minimal inhibitory concentration (MIC) of tedizolid against a collection of 359 clinical isolates involved in clinically-documented BJIs and to compare them to those of comparator agents used in Gram-positive infections. Of the 104 Staphylococcusaureus and 102 coagulase-negative staphylococci (CoNS) isolates, 99 and 92 % were categorized as susceptible to tedizolid, respectively (MIC25=0.12/0.25 µg ml

Topics: Anti-Bacterial Agents; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Joint Diseases; Microbial Sensitivity Tests; Organophosphates; Osteomyelitis; Oxazoles

We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bone Wires; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Foreign Bodies; Injections, Intraperitoneal; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Organophosphates; Osteomyelitis; Oxazoles; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tibia; Vancomycin