New Antibiotics for Acute Bacterial Skin Infections
The oxazolidinones are a synthetic class of agents now commonly relied on for the treatment of ABSSSIs, including more serious infections like MRSA and VRE. With increasing utilization of linezolid, resistant pathogens have begun to emerge. Tedizolid phosphate is a second-generation oxazolidinone antibiotic that offers enhanced antimicrobial potency and low rates of bacterial resistance. Available in both IV and oral forms, tedizolid exhibits bacteriostatic activity by binding the 50S subunit of the bacterial ribosome, resulting in inhibition of bacterial protein synthesis. The recommended dosage is 200 mg once daily for 6 days, which may offer increased convenience and compliance when compared to twice daily linezolid.
Clinical studies have proven tedizolid phosphate to be effective against susceptible isolates of gram-positive organisms including S. aureus (including MRSA and MSSA), various Streptococcus groups (S. pyogenes, S. agalactiae, and S. anginosus), and E. faecalis (including VRE).In vitro studies have suggested it may also exhibit activity against some strains of Staphylococci and Enterococci that are not susceptible to vancomycin or linezolid; however, the clinical importance of this data has not been established. The safety and effectiveness in pediatric patients 18 years of age or younger has not been demonstrated; whereas, linezolid is indicated for use in pediatric patients. Tedizolid phosphate is pregnancy category C.
Structural differences between tedizolid and linezolid are thought to contribute to tedizolid's decreased rates of resistance and enhanced potency. Bacteria confer resistance to linezolid by acquiring the chloramphenicol-florfenicol resistance gene, which can be horizontally transferred. However, because of structural distinctions, tedizolid has decreased vulnerability to this resistance mechanism. Interactions with the ribosomal subunit are thought to contribute to the increased potency of tedizolid.
Another potential advantage of tedizolid compared to linezolid is an improved safety profile. The most common adverse effects are similar to those seen with linezolid and include nausea, headache, diarrhea, vomiting, and dizziness, each occurring in less than 8% of patients. Toxicity linked to duration of treatment with linezolid includes peripheral and optic neuropathy as well as hematologic toxicity and thrombocytopenia. Tedizolid has not had reports of peripheral and optic neuropathy. Although tedizolid exposure has been limited to 21 days or less in patients, a rat study using tedizolid doses up to 10-fold greater than human doses did not induce a neuropathy. This data indicates a possible safety advantage of tedizolid. Additionally, at recommended doses, tedizolid has not been associated with hematologic toxicity or thrombocytopenia; however, higher doses or longer treatment durations might increase the risk. Linezolid has been associated with the occurrence of myelosuppression, especially in patients who have underlying hematologic abnormalities or renal insufficiency, which requires complete blood counts to be monitored weekly. An additional concern exists for the oxazolidinone class, which has been shown to act as weak, reversible monoamine oxidase (MAO) inhibitors in some in vitro studies. However, based on two randomized, double-blind, placebo-controlled crossover studies, as well as another study including both humans and animals, tedizolid failed to interact with serotonergic drugs, adrenergic agents, or result in MAO inhibitor activity. Data from post marketing experience will be beneficial to confirm the encouraging results that are currently available.
Oxazolidinone Therapeutic - Tedizolid Phosphate
The oxazolidinones are a synthetic class of agents now commonly relied on for the treatment of ABSSSIs, including more serious infections like MRSA and VRE. With increasing utilization of linezolid, resistant pathogens have begun to emerge. Tedizolid phosphate is a second-generation oxazolidinone antibiotic that offers enhanced antimicrobial potency and low rates of bacterial resistance. Available in both IV and oral forms, tedizolid exhibits bacteriostatic activity by binding the 50S subunit of the bacterial ribosome, resulting in inhibition of bacterial protein synthesis. The recommended dosage is 200 mg once daily for 6 days, which may offer increased convenience and compliance when compared to twice daily linezolid.
Clinical studies have proven tedizolid phosphate to be effective against susceptible isolates of gram-positive organisms including S. aureus (including MRSA and MSSA), various Streptococcus groups (S. pyogenes, S. agalactiae, and S. anginosus), and E. faecalis (including VRE).In vitro studies have suggested it may also exhibit activity against some strains of Staphylococci and Enterococci that are not susceptible to vancomycin or linezolid; however, the clinical importance of this data has not been established. The safety and effectiveness in pediatric patients 18 years of age or younger has not been demonstrated; whereas, linezolid is indicated for use in pediatric patients. Tedizolid phosphate is pregnancy category C.
Structural differences between tedizolid and linezolid are thought to contribute to tedizolid's decreased rates of resistance and enhanced potency. Bacteria confer resistance to linezolid by acquiring the chloramphenicol-florfenicol resistance gene, which can be horizontally transferred. However, because of structural distinctions, tedizolid has decreased vulnerability to this resistance mechanism. Interactions with the ribosomal subunit are thought to contribute to the increased potency of tedizolid.
Another potential advantage of tedizolid compared to linezolid is an improved safety profile. The most common adverse effects are similar to those seen with linezolid and include nausea, headache, diarrhea, vomiting, and dizziness, each occurring in less than 8% of patients. Toxicity linked to duration of treatment with linezolid includes peripheral and optic neuropathy as well as hematologic toxicity and thrombocytopenia. Tedizolid has not had reports of peripheral and optic neuropathy. Although tedizolid exposure has been limited to 21 days or less in patients, a rat study using tedizolid doses up to 10-fold greater than human doses did not induce a neuropathy. This data indicates a possible safety advantage of tedizolid. Additionally, at recommended doses, tedizolid has not been associated with hematologic toxicity or thrombocytopenia; however, higher doses or longer treatment durations might increase the risk. Linezolid has been associated with the occurrence of myelosuppression, especially in patients who have underlying hematologic abnormalities or renal insufficiency, which requires complete blood counts to be monitored weekly. An additional concern exists for the oxazolidinone class, which has been shown to act as weak, reversible monoamine oxidase (MAO) inhibitors in some in vitro studies. However, based on two randomized, double-blind, placebo-controlled crossover studies, as well as another study including both humans and animals, tedizolid failed to interact with serotonergic drugs, adrenergic agents, or result in MAO inhibitor activity. Data from post marketing experience will be beneficial to confirm the encouraging results that are currently available.