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Continuous infusion of piperacillin/tazobactam in ventilator-associated pneumonia: a pilot study on efficacy and
Wieslawa Duszynska1, Fabio Silvio Taccone, Marcin Switala
1Department of Anesthesiology and Intensive Care, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland. w.duszynska@onet.eu
Abstract:
Ventilator-associated pneumonia (VAP) occurs in nearly one-third of mechanically ventilated patients in the Intensive Care Unit. Piperacillin/tazobactam (TZP) is currently recommended in the empirical treatment of VAP, but intermittent dosing may result in inadequate serum concentrations. The efficacy and costs of continuous infusion (CI) of TZP, using therapeutic drug monitoring for real-time dose adjustment, was assessed in a prospective pilot study of 16 patients with VAP. TZP was given as a loading dose of 2.0/0.25 g followed by a CI of 10.0/1.25g daily. Rapid antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration (MIC) of the pathogens. TZP concentrations were determined by high-pressure liquid chromatography before and at 1, 6, 12, 24, 48, 72 and 96 h after the onset of administration. Dosages were adjusted to maintain piperacillin concentrations four-fold above the MIC (T>4 × MIC) of the pathogen, with a maximum dose of 16.0/2.0 g. The cost of the total TZP administered was compared with the cost of a standard TZP regimen (16.0/2.0 g) if given over the same period of time. The median MIC for TZP was 1 μg/mL (range 0.025-32 μg/mL). TZP concentrations were adequate for 71% of pathogens on the first day of therapy. Clinical cure was achieved in 9/10 patients who had adequate drug concentrations and in 3/6 patients with insufficient levels. The daily dose of TZP received by CI was 37.5% less than that of a standard regimen, which corresponds to a saving of €15 on daily therapy costs compared with the standard regimen. In conclusion, CI of TZP achieved optimal drug concentrations in most patients with VAP, with a favourable impact on costs. Adequate drug concentrations were achieved for MIC ≤ 4 μg/mL, but higher dosages should be considered for the treatment of pathogens with low susceptibility thresholds.
Insights
Continuous infusion of piperacillin/tazobactam (TZP) effectively treats ventilator-associated pneumonia (VAP) by maintaining optimal drug levels. This method also reduces therapy costs compared to standard intermittent dosing, making it a cost-effective VAP treatment strategy.
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Ventilator-associated pneumonia (VAP) affects nearly one-third of mechanically ventilated ICU patients.
- Current piperacillin/tazobactam (TZP) intermittent dosing may lead to inadequate serum concentrations for VAP treatment.
- Optimizing antibiotic delivery is crucial for improving patient outcomes and managing antimicrobial resistance.
Purpose of the Study:
- To assess the efficacy and cost-effectiveness of continuous infusion (CI) piperacillin/tazobactam (TZP) in VAP patients.
- To evaluate the impact of therapeutic drug monitoring on real-time dose adjustment for TZP therapy.
- To compare the costs of CI TZP with standard intermittent dosing regimens.
Main Methods:
- A prospective pilot study involving 16 VAP patients receiving TZP via CI.
- Loading dose followed by CI, with dosages adjusted based on rapid antimicrobial susceptibility testing and piperacillin MIC.
- High-performance liquid chromatography used for real-time piperacillin concentration monitoring.
- Cost analysis comparing CI TZP with standard regimens.
Main Results:
- Continuous infusion TZP achieved adequate drug concentrations for 71% of pathogens on day one.
- Clinical cure rates were higher in patients with adequate drug concentrations (9/10) versus insufficient levels (3/6).
- CI TZP resulted in a 37.5% lower daily dose and a saving of €15 per day compared to standard regimens.
Conclusions:
- Continuous infusion of TZP is effective in achieving optimal drug concentrations for most VAP patients.
- CI TZP demonstrates a favorable impact on treatment costs.
- Adequate concentrations were achieved for MIC ≤ 4 μg/mL; higher doses may be needed for pathogens with lower susceptibility thresholds.
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