Review ArticlePharmacokinetics and Clinical Use of Cephalosporin Antibiotics
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The potential impact of discrepancies between automated susceptibility platforms and other testing metho`dologies for cefazolin in the treatment of Enterobacterales bloodstream infections
2021, Diagnostic Microbiology and Infectious DiseaseCitation Excerpt :Turnidge, 2011) Based on the previous Monte Carlo simulations and consideration of commonly used clinical dosing strategies, it was suggested that the breakpoints be increased by 1, 2-fold dilution (susceptible, ≤2 µg/mL; intermediate, 4 µg/mL; and resistant, >8 µg/mL) based on a dosing strategy of CFZ 2g q8h, leading to a probability of target attainment (PTA) of greater than 90%. ( Nightingale et al., 1975; Scheld et al., 1981; Turnidge, 2011) Though the CLSI revised these breakpoints years ago, the FDA has yet to recognize the adjustment. ( Research C for DE and. Cefazolin 2018) Due to regulatory issues and practical limitations of approved automated susceptibility testing (AST) platforms, this has resulted in difficulties in clinical application of AST results. (
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Cephalexin Monohydrate
2020, Journal of Pharmaceutical SciencesGraphene Oxide–Based Nanocomposite for Sustained Release of Cephalexin
2020, Journal of Pharmaceutical SciencesThe impact of revised CLSI cefazolin breakpoints on the clinical outcomes of Escherichia coli bacteremia
2016, Journal of Microbiology, Immunology and InfectionCitation Excerpt :The choice of cefazolin breakpoints (susceptible, ≤ 1 μg/mL) was based on the conventional dose of cefazolin (i.e., 1 g every 8 hours) according to Monte Carlo Simulation in two pharmacokinetic studies of cefazolin.3,4 However, the target attainment rates for 50% T > MIC can achieve 94∼100% at the dose of 2 g every 8 hours suggested that a breakpoint of susceptibility of ≤ 2 μg/mL may be acceptable.3,4 To prevent the impact of eliminating cefazolin as a useful agent for the treatment and prevention of infections caused by some common Enterobacteriaceae without a resistance mechanism, the breakpoints of cefazolin for Enterobacteriaceae were further revised by the CLSI in 2011 (i.e., susceptible, ≤ 2 μg/mL; intermediate, 4 μg/mL; and resistant, ≥ 8 μg/mL, based on a dosage regimen of 2 g every 8 hours).5,6
Impact of revised susceptibility breakpoints on bacteremia of Klebsiella pneumoniae: Minimum inhibitory concentration of cefazolin and clinical outcomes
2016, Journal of Microbiology, Immunology and InfectionCitation Excerpt :According to PK-PD data, the cefazolin susceptibility breakpoint of 2 μg/mL based on a higher dosage regimen (2 g every 8 hours) was suggested by CLSI 2011.28 The decision for the revised breakpoints by CLSI 201128 was based on the Monte Carlo simulation analysis.26,27 The target attainment rates for 50% T > MIC can achieve 94% for the isolates with a cefazolin MIC of 1 μg/mL and 64% for those of 2 μg/mL at the conventional dose regimen of 1 g every 8 hours.26