Abstract
Tedizolid and linezolid have antibacterial activity against the most important acute bacterial skin and skin-structure infection (ABSSSIs) pathogens. The objective of this work was to apply PK/PD analysis to evaluate the probability of attaining the pharmacodynamic target of these antimicrobials based on the susceptibility patterns of different clinical isolates causing ABSSSI. Pharmacokinetic and microbiological data were obtained from the literature. PK/PD breakpoints, the probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated by Monte Carlo simulation. PTA and CFR are indicative of treatment success. PK/PD breakpoints of tedizolid and linezolid were 0.5 and 1 mg/L, respectively. Probability of treatment success of tedizolid was very high (>90%) for most staphylococci strains, including MRSA and coagulase-negative staphylococci (CoNS). Only for methicillin- and linezolid-resistant S. aureus (MLRSA) and linezolid resistant (LR) CoNS strains was the CFR of tedizolid very low. Except for LR, daptomycin-non-susceptible (DNS), and vancomycin-resistant (VRE) E. faecium isolates, tedizolid also provided a high probability of treatment success for enterococci. The probability of treatment success of both antimicrobials for streptococci was always higher than 90%. In conclusion, for empiric treatment, PK/PD analysis has shown that tedizolid would be adequate for most staphylococci, enterococci, and streptococci, even those LR whose linezolid resistance is mediated by the cfr gene.
Highlights
Linezolid, the first commercialized oxazolidinone antibiotic, has activity against a wide variety of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus [1].Regardless of the patient’s hepatic or renal function, the authorized dose of linezolid is 600 mg every 12 h
Work, we we evaluated evaluated by the activof tedizolid and compared it to linezolid, with the objective of predicting the probability ity of tedizolid and compared it to linezolid, with the objective of predicting the probabil- of treatment success considering the susceptibility profile of of staphylococci, ity of treatment success considering the susceptibility profile staphylococci,enterococci, enterococci,and streptococci reported in Europe andand the the and streptococci reported in Europe
The first representative member of the oxazolidinone family introduced into the pharmaceutical market, shows excellent activity; in recent years, resistance to microorganisms has emerged [31]
Summary
The first commercialized oxazolidinone antibiotic, has activity against a wide variety of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus [1].Regardless of the patient’s hepatic or renal function, the authorized dose of linezolid is 600 mg every 12 h. The first commercialized oxazolidinone antibiotic, has activity against a wide variety of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus [1]. Tedizolid phosphate is the second commercially available oxazolidinone antibiotic, with antibacterial activity against the most important acute bacterial skin and skin-structure infection (ABSSSIs) pathogens, including some linezolid-resistant. Like linezolid, inhibits bacterial protein synthesis by binding to 23S rRNA of the 50S subunit of the ribosome. It has been approved in several countries, including the United States, the European Union, and Canada [3]. The dose of tedizolid does not need to be modified in patients with renal impairment, hepatic impairment, on hemodialysis, or whenever switching from intravenous to oral administration [6]
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