By Nightingale C.H., et al. (eds.)
Taking readers from the examine laboratory to the bedside, this moment version compiles crucial details at the pharmacodynamics of all significant sessions of the antimicrobial armamentarium together with penicillins, cephalosposorins, cephamycins, carbapenems, monobactams, aminoglycosides, quinolones, macrolides, antifungals, antivirals, and rising brokers at present in improvement. Written through skilled pros within the box, this advisor makes use of an abundance of examples to depict how you can observe pharmacodynamic innovations to daily scientific perform.
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Additional resources for Antimicrobial pharmacodynamics in theory and clinical practice
By integrating PK with PD properties of the drug–microorganism interaction, PK–PD relationships could be established and subsequently used for evaluating dosing regimens, development of new drugs, and the setting of susceptibility breakpoints. Thus, today, we recognize that the effect of changing drug concentration over time is fundamentally different for various classes of antibiotics, and in most cases, is directly related to the pattern of bactericidal activity (16). As can be observed from Figure 1, the concentration–time curve of a drug possesses three major characteristics or PK–PD indices: the ratio of the peak or maximal concentration (Cmax) to the MIC value of the drug to the pathogen (Cmax: MIC), the ratio of the area under the concentration–time curve at 24 hours (AUC) to the MIC value of the drug to the pathogen (AUC:MIC), and the duration of time the drug concentration remains above the MIC value of the drug to the pathogen (T>MIC).
Int J Antimicrob Agents 1999; 12(2):107–114. Bedos JP, Rieux V, Bauchet J, Muffat-Joly M, Carbon C, Azoulay-Dupuis E. Efficacy of trovafloxacin against penicillin-susceptible and multiresistant strains of Streptococcus pneumoniae in a mouse pneumonia model. Antimicrob Agents Chemother 1998; 42(4):862–867. Bedos JP, Azoulay-Dupuis E, Moine P, et al. Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine pneumococcal pneumonia model: relevance for drug efficacy. J Pharmacol Exp Ther 1998; 286(1):29–35.
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.
Antimicrobial pharmacodynamics in theory and clinical practice by Nightingale C.H., et al. (eds.)