Ceftolozane/Tazobactam for Pseudomonas aeruginosa Infections: Going Beyond the Package Insert

Shmuel Shoham, MD; Patricia J. Simner, PhD; Kathryn E. Dzintars, PharmD

Disclosures

February 09, 2016

In This Article

Ceftolozane/Tazobactam for Treatment of Pneumonia

  • Is the FDA-approved dose (1.5 g intravenously every 8 hours) adequate for a lung infection? Probably not.

Data on use of ceftolozane/tazobactam in the critically ill population are limited. However, a phase 3 trial is currently under way investigating its use in the management of hospital-acquired or ventilator-associated pneumonia.[9] That trial is using a dosage of 3 g every 8 hours. Furthermore, a small, single-center case series[10] has documented clinical success in three patients with pneumonia using higher doses of ceftolozane/tazobactam, highlighting the promising future that this agent may have.

The rationale for the higher dose is the observation that ceftolozane/tazobactam levels in the lung are about 50% of those in plasma.[11] Using a population pharmacokinetic model with Monte Carlo simulations, it was determined that for patients with normal renal function, a 3-g dose of ceftolozane/tazobactam will attain the required pulmonary drug levels needed to kill 90% of organisms with a MIC of ≤ 8 mg/L 98% of the time.[12]

Hopefully, the results of the large study will provide more informative data, but these are unlikely to be available for some time. In the interim, if ceftolozane/tazobactam is to be used for patients with pneumonia, the appropriate starting dosage should be 3 g every 8 hours, adjusted further according to renal function.

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