Tedizolid Disease Interactions

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

The antibacterial activity of tedizolid may be reduced in the absence of granulocytes. In the mouse thigh infection model of Staphylococcus aureus, bacterial stasis was achieved in non-granulocytopenic mice at a human-equivalent dose of approximately 100 mg/day, whereas a human-equivalent dose of approximately 2000 mg/day was required in granulocytopenic mice with neutrophil count less than 100 cells/mL. The safety and efficacy of tedizolid in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. Alternative antibiotics should be considered in neutropenic patients who require treatment for acute bacterial skin and skin structure infections.