Use of continuous-infusion ceftolozane/tazobactam for resistant Gram-negative bacterial infections: a retrospective analysis and brief review of the literature.

Abstract Introduction Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin with beta-lactamase inhibitor, is used in multidrug-resistant gram-negative infections. Continuous infusion (CI) C/T is an attractive concept, for aiding in transitions of care and maximizing pharmacodynamics of cephalosporins (T>MIC). Methods This was a single-center, retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting. Safety and effectiveness were assessed. When therapeutic drug monitoring (TDM) was performed, area under the concentration curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. Results CI C/T was used in 7 unique regimens over the 30-month evaluation period. Patient's age ranged 23 to 70 years and indication was primarily for treatment of deep-seated infections caused by multidrug-resistant Pseudomonas aeruginosa. Four regimens (57%) were used for outpatient transitions of care. The typical dose was 6 grams every 24 hours, although a renally adjusted dose was used in 2 instances (28%). TDM was performed in 4 (57%) uses and target attainment was confirmed in 100%. Ceftolozane AUC ranged 365.7 – 818.2mcg•(h/mL). All patients had positive outcomes with no significant adverse events. One patient developed acute gout flares. One patient had recurrent infection with C/T-resistant P. aeruginosa after ∼3 months of reduced dose for suppression. Discussion CI C/T was successfully utilized for deep-seated infections in the inpatient and outpatient setting. TDM confirmed CI C/T achieved pharmacodynamic targets for the entire dosing interval suggesting an effective alternative dosing regimen applicable across the continuum of care.