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Maximally effective dosing regimens of meropenem in patients with septic shock

Sjövall, Fredrik LU ; Alobaid, Abdulaziz S.; Wallis, Steven C.; Perner, Anders; Lipman, Jeffrey and Roberts, Jason A. (2018) In Journal of Antimicrobial Chemotherapy 73(1). p.191-198
Abstract

Objectives: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. Methods: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. Results: Fifty patients were... (More)

Objectives: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. Methods: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. Results: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of≤100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. Conclusions: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.

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type
Contribution to journal
publication status
published
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in
Journal of Antimicrobial Chemotherapy
volume
73
issue
1
pages
8 pages
publisher
Oxford University Press
external identifiers
  • scopus:85040607406
ISSN
0305-7453
DOI
10.1093/jac/dkx330
language
English
LU publication?
yes
id
a3ae2f39-50d6-4aba-a11b-b3897ab3e2ad
date added to LUP
2018-02-26 17:31:25
date last changed
2018-05-29 09:51:45
@article{a3ae2f39-50d6-4aba-a11b-b3897ab3e2ad,
  abstract     = {<p>Objectives: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. Methods: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. Results: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CL<sub>CR</sub>) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CL<sub>CR</sub> of≤100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. Conclusions: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.</p>},
  articleno    = {dkx330},
  author       = {Sjövall, Fredrik and Alobaid, Abdulaziz S. and Wallis, Steven C. and Perner, Anders and Lipman, Jeffrey and Roberts, Jason A.},
  issn         = {0305-7453},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {191--198},
  publisher    = {Oxford University Press},
  series       = {Journal of Antimicrobial Chemotherapy},
  title        = {Maximally effective dosing regimens of meropenem in patients with septic shock},
  url          = {http://dx.doi.org/10.1093/jac/dkx330},
  volume       = {73},
  year         = {2018},
}