Profile of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections.

Tedizolid phosphate is the first once-daily oxazolidinone approved by the United States Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections (ABSSSI). It is more potent in vitro than linezolid against methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive pathogens causing ABSSSI, even retaining activity against some linezolid-resistant strains. Tedizolid is approximately 90% protein bound, leading to lower free-drug concentrations than linezolid. The impact of the effect of food, renal or hepatic insufficiency, or hemodialysis on tedizolid's pharmacokinetic have been evaluated, and no dosage adjustment is needed in these populations. In animal and clinical studies, tedizolid's effect on bacterial killing is optimized by the free-drug area under the curve to minimum inhibitory concentration ratio (fAUC/MIC). The 200 mg once-daily dose is able to achieve the target fAUC/MIC ratio in 98% of simulated patients. Two Phase III clinical trials have demonstrated the noninferiority of tedizolid 200 mg once daily for 6 days to linezolid 600 mg twice daily for 10 days. In vitro, animal, and clinical studies have failed to demonstrate that tedizolid inhibits monoamine oxidase to a clinically relevant extent. Tedizolid has several key advantages over linezolid including once daily dosing, decreased treatment duration, minimal interaction with serotonergic agents, possibly associated with less adverse events associated with the impairment of mitochondrial protein synthesis (eg, myelosuppression, lactic acidosis, and peripheral/optic neuropathies), and retains in vitro activity against linezolid-resistant gram-positive bacteria. Economic analyses with tedizolid are needed to describe the cost-effectiveness of this agent compared with other options used for ABSSSI, particularly treatment options active against MRSA.

Is it time to call it quits on low-dose quetiapine?

The mandate of the Centers for Medicare & Medicaid Services to decrease the use of antipsychotics in long-term care facilities requires creative solutions. Low-dose quetiapine is used for a multitude of behavioral disorders and sleep problems in the nursing facility population. Yet, at doses of 25 mg per day or less, it doesn't have strong affinity (if any) for the dopamine-2 (D2) receptor, but it does maintain affinity for the histamine-1 and alpha-1 receptors. This begs the question: If it's not antagonizing the D2 receptor, could the use of something with similar receptor-affinity produce the same result, allowing discontinuation of the antipsychotic altogether? Using knowledge of receptor affinities and the pharmacologic action of low-dose quetiapine, consultant pharmacists may have one additional tool in their armamentarium of fighting inappropriate antipsychotic use.