tedizolid and Neutropenia

Linezolid is used to treat prosthetic joint infection after total hip arthroplasty. Here, we present a case of linezolid-induced severe neutropenia, which improved after switching to tedizolid. Grade 3 neutropenia developed 5 days after linezolid injection (1,200 mg/day) and 33 days after oral administration of the same dose. However, during the 70 days of treatment with tedizolid, grade 3 neutropenia did not occur, and C-reactive protein levels remained in the normal range. No grade ≥ 1 thrombocytopenia or bleeding event occurred during the course of tedizolid treatment. Tedizolid may be an alternative drug for patients who develop linezolid-induced neutropenia.

Topics: Anti-Bacterial Agents; Humans; Linezolid; Microbial Sensitivity Tests; Neutropenia; Organophosphates; Oxazoles; Oxazolidinones; Skin Diseases, Bacterial; Tetrazoles

Few antibiotics are approved to treat Staphylococcus aureus pneumonia. Tedizolid is an oxazolidinone with potent in vitro activity against S. aureus and is currently under investigation for hospital-acquired and ventilator-associated bacterial pneumonia. Limited data exist on the comparative efficacy of tedizolid versus current first-line treatments vancomycin and linezolid in the compromised host. Our objective was to compare the efficacy of human-simulated epithelial lining fluid (ELF) exposures of tedizolid, linezolid and vancomycin against S. aureus in neutropenic and immunocompetent murine pneumonia models.. Eight S. aureus isolates (four MRSA and four MSSA) were studied. Neutropenic and immunocompetent mice were inoculated intranasally with bacterial suspensions of 107 and 109 cfu/mL, respectively, then treated for up to 72 h with model-specific regimens of tedizolid, linezolid and vancomycin simulating human ELF exposures after clinical doses. Mice were sacrificed at 24, 48 or 72 h and changes in log10 cfu/lungs were compared with 0 h controls.. Mean bacterial burdens at 0 h were 5.81 and 8.17 log10 cfu/lungs for neutropenic and immunocompetent mice, respectively, and increased at 24 h in the absence of antibiotic treatment to 7.97 and 9.00 log10 cfu/lungs, respectively. In neutropenic and immunocompetent mice, tedizolid was associated with bacterial density changes of -2.69 ± 0.62 and -3.57 ± 0.88 log10 cfu/lungs at 72 h, respectively. In both models, tedizolid treatment produced greater bacterial reductions than vancomycin and was not statistically significantly different from linezolid.. Human-simulated ELF exposures of tedizolid demonstrated sustained efficacy in compromised and competent models of pneumonia. Validation of these findings in patients is warranted.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Disease Models, Animal; Female; Linezolid; Lung; Mice, Inbred BALB C; Neutropenia; Oxazolidinones; Pneumonia, Staphylococcal; Protein Synthesis Inhibitors; Tetrazoles; Treatment Outcome; Vancomycin