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Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion

https://doi.org/10.1016/j.ijantimicag.2008.10.025Get rights and content

Abstract

The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as β-lactam antibiotics exhibit time-dependent antibacterial activity. In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime. Therefore, the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure. Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 μg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR) = 10.79, 95% confidence interval (CI) 1.01–588.24; P = 0.049] or 16 μg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR = 22.89, 95% CI 1.19–1880.78; P = 0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8–16 μg/mL in patients without renal failure.

Introduction

The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous for several reasons: (i) the primary determinant of β-lactam antibacterial activity is the duration of time that blood concentrations remain above the minimum inhibitory concentration (MIC) [1]; and (ii) administration of β-lactams by continuous infusion provides serum concentrations exceeding the MIC more consistently than has been reported for intermittent infusion [2]. However, there are limited data on the clinical efficacy of piperacillin administered by continuous infusion [3], [4], [5], [6], [7].

In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion than intermittent infusion of meropenem [8] and ceftazidime [9].

The objective of this study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous infusion compared with intermittent infusion in the treatment of adult patients with VAP caused by Gram-negative bacilli and without renal failure.

Section snippets

Patients and methods

This historical cohort study was conducted at the Medical–Surgical Intensive Care Unit (ICU) of the Hospital Universitario de Canarias, Tenerife, Spain.

The clinical histories of patients with VAP caused by Gram-negative bacteria who received initial empirical antibiotic therapy with PIP/TAZ over a 5-year period (June 2002 to December 2007) were retrieved from the patient database of the ICU. All of the following criteria had to be met for a diagnosis of VAP: chest radiography indicating new or

Results

No significant differences were found between the continuous infusion (n = 37) and intermittent infusion (n = 46) groups in terms of sex, age, COPD, APACHE II score at ICU admission, diagnosis, microorganism responsible for VAP, weight, CLCr, SOFA score at the time of suspected VAP, vasopressor use, steroid use or the MIC of the responsible organism. The continuous infusion group had a significantly higher clinical cure rate than the intermittent infusion group [33/37 (89.2%) vs. 26/46 (56.5%); P = 

Discussion

Administration of PIP/TAZ by continuous infusion as opposed to intermittent infusion may be pharmacodynamically advantageous because the percentage of time during which the PIP/TAZ plasma concentration remains above the MIC (%T > MIC) is higher by continuous infusion [3], [7], [16].

In a study by Rafati et al. [3], 40 septic critically ill patients were randomised to receive piperacillin by continuous infusion (2 g over 0.5 h as a loading dose, followed by 8 g daily over 24 h) or by intermittent

Conclusion

In this retrospective study of patients without renal failure, administration of PIP/TAZ by continuous infusion showed a higher rate of clinical cure than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the causative microorganism was 8–16 μg/mL. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion. However, before changing the standard mode of administering β-lactams, randomised

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