Intrapulmonary penetration of ceftolozane/tazobactam and ceftazidime/avibactam administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial
Authors' conclusion
In critically ill adults with nosocomial pneumonia receiving TOL/TAZ or CAZ/AVI by CI, standard doses achieved ELF exposures consistent with dual PK/PD target attainment against all susceptible isolates.
Study context
- Population
- Critically ill patients with nosocomial pneumoniarandomized 1:1
- Participants
- 30 patients
- Comparison
- TOL/TAZ 6 g/3 g vs CAZ/AVI 6 g/1.5 g by continuous infusion
- Primary endpoint
- ELF penetration (AUC0-8ELF/AUC0-8plasma) and PK/PD target attainment
Methodological detailssingle-centre, open-label, pharmacokinetic study, population pharmacokinetic (PK) model, simulations, 298 plasma and 58 epithelial lining fluid (ELF) samples analysed
- Single-centre
- Open-label
- Pharmacokinetic study
- Population PK model
- Simulations
- 298 plasma and 58 ELF samples analysed
Primary result
As reported in the abstract
Intrapulmonary penetration (AUC0-8ELF/AUC0-8plasma)
| Group | Value | Tazobactam penetration, median [IQR] | Avibactam penetration, median [IQR] |
|---|---|---|---|
| TOL/TAZ | median 0.66 (IQR 0.32) | 0.44 [0.05] | |
| CAZ/AVI | median 0.41 (IQR 0.30) | 0.44 [0.46] |
Value
TOL/TAZmedian 0.66 (IQR 0.32)
CAZ/AVImedian 0.41 (IQR 0.30)
Tazobactam penetration, median [IQR]
TOL/TAZ0.44 [0.05]
CAZ/AVI— not stated in the abstract
Avibactam penetration, median [IQR]
TOL/TAZ— not stated in the abstract
CAZ/AVI0.44 [0.46]
Further findings
Simulated ELF target attainment by dosing regimen (low, standard, high)
- All CAZ/AVI regimens achieved high ELF target attainment (ceftazidime minimum inhibitory concentration (MIC) 8 mg/L, avibactam concentration threshold (CT) 1 mg/L)
- TOL/TAZ required at least the standard-dose regimen (ceftolozane MIC 4 mg/L, tazobactam CT 2 mg/L)
- More aggressive targets reduced target attainment, particularly inhibitor thresholds of 4 mg/L and Enterobacterales-oriented joint targets
Original publication
Intrapulmonary penetration of ceftolozane/tazobactam and ceftazidime/avibactam administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial. Crit Care. Published 13 May 2026. doi:10.
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