Monday May 12, 2008
On Zosyn's (Piperacillin/tazobactam) dose in nosocomial and ventilator-associated pneumonia

Does Piperacillin/tazobactam (Zosyn) reaches adequate alveolar concentration (as needed in nosocomial and ventilator-associated pneumonia) at any dose of continuous infusion? Recent study by Emmanuel helped to address this issue.

Patients: 40 patients with microbiologically documented ventilator-associated pneumonia (VAP).

Interventions: Patients were randomized to receive piperacillin/tazobactam daily continuous infusions of

• 12/1.5 g/day or
• 16/2 g/day after a loading dose of 4/0.5 g

The serum and alveolar piperacillin/tazobactam concentrations were determined at steady-state with high performance liquid chromatography.

Conclusions: A target piperacillin serum concentration of at least 35-40 mg/L is probably required to provide alveolar concentrations exceeding the susceptibility breakpoint for Gram-negative bacteria (16 mg/L) during ventilator-associated pneumonia.

In patients with no/mild renal failure, a continuous daily dose of piperacillin/tazobactam 16/2 g/day allows reaching this target concentration, which might be not observed with 12/1.5 g/day.

In patients with moderate/advanced renal failure, both dosages achieve serum concentrations far above the 35-40 mg/L threshold, suggesting that in that case, therapeutic drug monitoring should be performed in order to adjust the daily dose.


Editors' comment: Zosyn is a frequent antibiotic used for Nosocomial and VAP(Ventilator associated Pneumonia) in USA but mostly in divided doses, instead of continuous infusion (as this study was done in France). This study translates into conclusion that patients with no renal insufficiency requires higher dose of Zosyn to treat Nosocomial and VAP (around 4.5 q 6 hours). But patients with renal insufficiency needs lower dose and drug monitoring is recommended.



reference: click to get abstract

Boselli E, Brelith D, Rimmele T, Guillaume C, Xuereb F, Saux MC, et al. Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia. Critical Care Medicine. 36(5):1500-1506, May 2008.