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PREDICTORS OF CEFTAZIDIME PK/PD INDEX TARGET VALUES AND TOXIC PLASMA LEVELS IN ADULT HOSPITALISED PATIENTS

SLOBODAN M. JANKOVIĆ 1,2, NEMANJA Z. PETROVIĆ 1,2*, DRAGAN MILOVANOVIĆ 1,2 , NIKOLA ROSIĆ 2, MIRJANA MILOJEVIĆ ČORBIĆ 2, MARKO FOLIĆ 2,3, DEJANA RUŽIĆ ZEČEVIĆ 1,2, RADICA ŽIVKOVIĆ ZARIĆ 1,2, SRĐAN STEFANOVIĆ 2,4, MLADEN PAVLOVIĆ 5 , SVETLANA OBRENOVIC 6, MARINA J. KOSTIĆ 1,7

1 Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
2 Department of Clinical Pharmacology, University Clinical Center Kragujevac, Kragujevac, Serbia
3 Center for Pharmaceutical and Pharmacological Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4 Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
5 Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
6 Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
7 Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

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The effectiveness of antibiotics in systemic bacterial infections depends not only on microbial sensitivity, but also on achieving adequate concentrations in tissues. This study aimed to identify predictors of achieving target pharmacokinetic/pharmacodynamic (PK/PD) values for ceftazidime and factors associated with toxic plasma concentrations. A cross-sectional observational study was conducted on hospitalised patients treated with ceftazidime for systemic bacterial infections at the University Clinical Centre Kragujevac (UKCK), Serbia, in 2024, as part of routine therapeutic drug monitoring. A total of 59 adult patients were included, each with at least two measurements of ceftazidime concentration per dosing interval. Forty-four patients achieved the target PK/PD value of fT above MIC, while 22 had toxic plasma concentrations. Male patients were less likely to achieve the target fT above MIC (adjusted OR = 0.07 [0.009 - 0.464]). Advanced age, elevated serum creatinine, and higher daily doses were associated with toxic concentrations. To ensure optimal efficacy and safety, ceftazidime dosing should be individualised based on sex, age, and renal function.