Pharmacokinetics of aztreonam/avibactam in a critically ill patient with a class B metallo-β-lactamase producing Enterobacteriaceae and receiving continuous renal replacement therapy

Carbapenem-resistant bacteria are among the most significant public health threats nowadays, with limited therapeutic options.1,2 Aztreonam/avibactam is a novel β-lactam/β-lactamase inhibitor combination recently licensed whose therapeutic role lies in the management of multidrug-resistant infections,3 especially those involving metallo-β-lactamases (MBLs). The optimization of pharmacokinetic/pharmacodynamic (PK/PD) properties of the antimicrobials, especially in certain populations and clinical conditions, can help to maximize efficacy and prevent toxicity and emergence of resistance.4,5 Like other β-lactam/β-lactamase inhibitors, the PK/PD target of aztreonam for critically ill patients has been defined as 100% of the dosing interval with free concentrations above the MIC (100% fT > MIC),6 with improved clinical outcomes when more aggressive PK/PD targets (%100 fT > 4×MIC) are achieved.7 For avibactam, it is recommended that plasma concentrations exceed the critical threshold (CT) concentration of 2–2.5 mg/L8 throughout the dosing interval. The PK of aztreonam/avibactam has been evaluated in patients with different degrees of renal impairment,3,9 but no data are available in those undergoing renal replacement therapy (RRT) other than haemodialysis (HD). Herein, we report the first case evaluating the PK/PD of aztreonam/avibactam, administered as a continuous infusion, in a critically ill patient undergoing continuous venovenous hemodiafiltration (CVVHDF).