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Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance

  • Pharmacodynamics
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Abstract

Introduction

Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC.

Materials and methods

In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days.

Results

Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement.

Conclusion

According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

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Notes

  1. Clinical Pulmonary Infection Score.

  2. Acute kidney injury.

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Funding

HPLC was funded by Tarbiat Modares University.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box, 14155-6153, Tehran, Iran

    Sareh Razzazzadeh, Jamshid Salamzadeh & Zahra Sahraei

  2. Department of Infectious Diseases and Tropical Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ilad Alavi Darazam

  3. Anesthesiology Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammadreaza Hajiesmaeili

  4. Departmant of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Arash Mahboubi

  5. Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Ehsan Sadeghnezhad

  6. Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Sahraei

Authors
  1. Sareh Razzazzadeh
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  2. Ilad Alavi Darazam
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  3. Mohammadreaza Hajiesmaeili
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  4. Jamshid Salamzadeh
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  5. Arash Mahboubi
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  6. Ehsan Sadeghnezhad
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  7. Zahra Sahraei
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Contributions

S. Razzazzadeh carried out sampling and calculations. I. Alavi Darazam evaluated clinical criteria. M. Hajiesmaeili provided administrative support for the clinical process. J. Salamzadeh performed statistical analysis. A. Mahboubi performed MIC assessments. E. Sadeghnezhad contributed to meropenem HPLC assay. Z. Sahraei conceived the original idea and the trial designing and was in charge of overall direction. All authors contributed to the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zahra Sahraei.

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Ethics approval

Institutional ethics approval was provided according to local protocols with the ethics committee code of IR.SBMU.PHARMACY.REC.1398.095. The trial was registered at the Iranian Registry of Clinical Trials with the registration number of IRCT20130917014693N12.

Conflict of interest

The authors declare no competing interests.

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Razzazzadeh, S., Darazam, I.A., Hajiesmaeili, M. et al. Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance. Eur J Clin Pharmacol 78, 823–829 (2022). https://doi.org/10.1007/s00228-022-03291-5

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  • DOI: https://doi.org/10.1007/s00228-022-03291-5

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