Zerbaxa

Columbia blood agar (COS) (bioMérieux) were used to culture the isolates. Cation-adjusted Mueller-Hinton broth (CA-MHB) (Becton, Dickinson) was used to perform the time-kill curves, and Mueller-Hinton agar (MH) plates (bioMérieux) were used for the quantification of CFU per milliliter.
The antibiotics used were meropenem, aztreonam, colistin, and amikacin (all from Sigma-Aldrich), and ceftolozane-tazobactam (Zerbaxa; MSD). The antibiotic stocks were prepared according to the Clinical and Laboratory Standards Institute (CLSI). The final concentrations used in the time-kill assays corresponded to the AUC over 24 h (Table 1) (17 (link)– (link)21 (link)).

Columbia blood agar (COS) (bioMérieux) were used to culture the isolates. Cation-adjusted Mueller-Hinton broth (CA-MHB) (Becton, Dickinson) was used to perform the time-kill curves, and Mueller-Hinton agar (MH) plates (bioMérieux) were used for the quantification of CFU per milliliter.
The antibiotics used were meropenem, aztreonam, colistin, and amikacin (all from Sigma-Aldrich), and ceftolozane-tazobactam (Zerbaxa; MSD). The antibiotic stocks were prepared according to the Clinical and Laboratory Standards Institute (CLSI). The final concentrations used in the time-kill assays corresponded to the AUC over 24 h (Table 1) (17 (link)– (link)21 (link)).

C/T (Zerbaxa; Merck & Co, Inc., Kenilworth, NJ; lot number SO15404; expiration date, August 2020) was provided by Merck & Co., Inc. (Kenilworth, NJ). The antibiotic solutions were prepared according to CLSI guidelines (24 ). The dosing regimens were within a dose range based on previously determined maximum concentration of drug in serum (C_max) and area under the curve (AUC) (21 (link)). Three regimens were simulated: 2 g/1 g every 8 h over 1 h (intermittent infusion) to reach a free C_max (fC_max) of 75 mg/L, 2 g/1 g every 8 h over 4 h (extended infusion) to reach an fC_max of 55 mg/L (10 (link)), and continuous infusion to reach a steady-state concentration of 45 mg/L. The simulated elimination half-life for ceftolozane was 3 h (14 (link), 21 (link)). Although tazobactam is present in the pharmaceutical formulation, exposure to this drug was not considered since it has a limited role in ceftolozane’s activity against P. aeruginosa (25 (link)). C/T concentrations were validated by high-performance liquid chromatography (HPLC) (26 (link)).