By Charles H. Nightingale, Paul G. Ambrose, George L. Drusano, Takeo Murakawa
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Additional resources for Antimicrobial Pharmacodynamics in Theory and Clinical Practice, 2nd Edition
In this chapter, we will discuss the meaning of S, I, and R in a historical context as well as provide the current view, based on PK–PD 21 22 Mouton et al. relationships. Both the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (3) and the Clinical and Laboratory Standards Institute [CLSI, formally known as the National Committee for Clinical Laboratory Standards (NCCLS)] consider PK–PD data in the selection of susceptibility breakpoints (4). HISTORY Initially, isolates were categorized as S or R largely based on MIC frequency distributions.
Report of an international collaborative study. Acta Pathol Microbiol Scand [B] Microbiol Immunol 1971; 217(suppl B):1–90. Soussy CJ, Cluzel R, Courvalin P. Definition and determination of in vitro antibiotic susceptibility breakpoints for bacteria in France. The Comite de l’Antibiogramme de la Societe Francaise de Microbiologie. Eur J Clin Microbiol Infect Dis 1994; 13(3):238–246. MacGowan AP, Wise R. Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests. J Antimicrob Chemother 2001; 48(suppl 1):17–28.
48. In the case of the cephalosporins with very low protein binding, ceftazidime, cefpirome, and cefotaxime all display values of 38% to 40% T>MIC, while if total concentrations of ceftriaxone, with a protein binding of 76% in mice, is considered, values needed are in the order of 70%. If the unbound fraction of ceftriaxone is considered, the effect is consistent with the other cephalosporins. Similarly, the AUC/MIC ratio needed for static effect of the highly protein-bound quinolones gemifloxacin and garenoxacin is comparable to that of the other quinolones only when the unbound fraction of the drug is taken into account.