Oxazolidinones

GENERAL PRINCIPLES

Oxazolidinones block assembly of bacterial ribosomes and inhibit protein synthesis. These agents demonstrate high oral bioavailability, allowing for PO therapy when available, and do not require dose adjustments for hepatic or renal dysfunction.

TREATMENT

• Linezolid (600 mg IV/PO q12h) has potent activity against gram-positive bacteria, including drug­resistant enterococci, staphylococci, and streptococci, but not against gram-negative bacteria. Linezolid is useful for treating serious infections caused by VRE, as an alternative to vancomycin for treatment of some MRSA infections, and as oral treatment of MRSA infections when IV access is unavailable. Linezolid should generally be avoided for catheter-related bloodstream or catheter site infections.

• Tedizolid (200 mg PO/IV q24h) is the newest oxazolidinone antibiotic available. It is FDA-approved for treating skin/soft tissue infections. Tedizolid's spectrum of activity is similar to linezolid, although tedizolid covers some linezolid-resistant Enterococcus spp.

SPECIAL CONSIDERATIONS

• Adverse events associated with linezolid include diarrhea, nausea, and headache. Myelosuppression, most commonly thrombocytopenia, occurs frequently in patients who receive ≥2 weeks of therapy. Thus, weekly CBC monitoring is indicated. Prolonged therapy has also been associated with peripheral and optic neuropathy. Lactic acidosis may also rarely occur. Adverse events associated with tedizolid are similar to linezolid, although its propensity to cause neuropathies and hematologic toxicities with prolonged use is unknown.

• Linezolid has several important drug interactions. It is a mild monoamine oxidase inhibitor and can cause serotonin syndrome when used in combination with other serotonergic agents. Patients should be advised to avoid selective serotonin reuptake inhibitors, other antidepressants, fentanyl, cyclobenzaprine, and meperidine while on linezolid. Ideally, patients should be off antidepressants for at least a week before initiating linezolid. Coadministration of pseudoephedrine with linezolid can elevate blood pressure and should also be avoided. Tedizolid appears less likely to inhibit monoamine oxidase as compared with linezolid; however, patients on serotonergic agents were excluded from tedizolid phase III clinical trials.