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

Abstract

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus β-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T_>MIC). This was a single-centre 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-time curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. CI C/T was used in seven unique regimens over the 31-month evaluation period. Patient age ranged from 23-70 years and the 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 g every 24 h, although a renally adjusted dose was used in two instances (29%). TDM was performed in four uses (57%) and target attainment was confirmed in each. Ceftolozane AUC ranged from 365.7-818.2 μg•(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. CI C/T was successfully utilised for deep-seated infections in inpatient and outpatient settings. TDM confirmed that CI C/T achieved pharmacodynamic targets for the entire dosing interval, suggesting an effective alternative dosing regimen applicable across the continuum of care.

Keywords: Ceftolozane/tazobactam; Continuous infusion; Pharmacodynamics; Pseudomonas aeruginosa.