The following is a summary of “A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF),” published in the April 2023 issue of the Critical Care by Gatti et al.

In critically ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF), Researchers aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for the treatment of difficult-to-treat resistant Gram-negative (DTR-GN) infections. Researchers looked at the records of CVVHDF patients treated with CI ceftazidime-avibactam for DTR-GN infections. The steady-state concentrations of ceftazidime and avibactam were measured, and the free fraction (fC_ss) was computed. The effect of CVVHDF intensity was evaluated using linear regression on the total clearance (CLtot) of both drugs. When both fCss/MIC4 for ceftazidime and fC_ss/CT >1 for avibactam was attained, the joint PK/PD target of ceftazidime-avibactam was considered to be ideal. Ceftazidime-avibactam pharmacokinetic/pharmacodynamic (PK/PD) endpoints and microbiological results were evaluated.

Researchers were able to reclaim eight patients with DTR-GN infections. The median fCss for ceftazidime was 84.5 mg/L (73.7-87.7 mg/L), whereas the median fC_ss for avibactam was 24.8 mg/L (20.7-25.8 mg/L). Both ceftazidime and avibactam had median CL_tot values of 2.39 L/h (2.05-2.96 L/h) and 2.56 L/h (2.12-2.98 L/h), respectively. Doses of CVVHDF ranged from 35.6 to 40.0 mL/kg/h (more commonly 38.6). Significant linear relationships were seen between CVVHDF dosage and CLtot (r = 0.53; P = 0.03 and r = 0.64; P = 0.006). All the evaluable instances achieved microbiological eradication because the combination of PK/PD objectives was optimal. Rapid achievement and maintenance of appropriate joint PK/PD objectives during high-intensity CVVHDF may be possible with CI administration of 1.25-2.5 g q8h ceftazidime-avibactam.

Source: sciencedirect.com/science/article/pii/S0883944123000503