A Retrospective Analysis of Pharmacokinetic-Pharmacodynamic Parameters as Indicators of the Clinical Efficacy of Ceftizoxime

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Abstract
To analyse the relationship between a series of estimated pharmaco-kinetic-pharmacodynamic parameters and the reported efficacy of ceftizoxime. Retrospective literature search and analysis using different correlation models. The following parameters were calculated for each group of patients included in the study from the simulated plasma concentration curves corresponding to the dosage regimen administered: (i) peak concentration at steady state divided by the minimum inhibitory concentration (Cmax SS/MIC); (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24 hours at steady state [(tss)24h > MIC]; (iii) the total area under the concentration-time curve over 24 hours at steady state divided by the MIC [(AUCss)24l/MIC]; and (iv) the AUC at steady state for the period of time that the concentration is above the MIC over a period of 24 hours divided by the MIC [(AUICss)24h]. A univariate correlation analysis was performed considering efficacy [rate (%) of clinical cure or bacterial eradication] as the dependent variable and the pharmacokinetic-pharmacodynamic parameter as the independent variable, using linear and nonlinear models. (tss)24h > MIC was the only parameter that was statistically correlated with efficacy, the linear model being the best choice among the 4 relationship approaches tested. A biased frequency distribution of reported efficacy data constricts the correlation analysis to a narrow range of efficacy and hinders interpretation of the results. The reporting of cases with low efficacy rates as well as those with high efficacy rates, including information on patient idiosyncrasies and the infecting organisms, would be of great help in performing retrospective analyses of the use of antimicrobial agents, leading to the optimisation of therapy with this type of drug in clinical practice.