Fredrik Sjövall1,2,3, Abdulaziz S Alobaid4,5, Steven C Wallis4, Anders Perner1,6, Jeffrey Lipman4,7,8, Jason A Roberts4,7,9. 1. Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 2. Department of Intensive Care and Perioperative Medicine, Skane University Hospital, Malmö, Lund University, Lund, Sweden. 3. Mitochondrial Medicine, Lund University, Lund, Sweden. 4. Burns Trauma and Critical Care Research Centre, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia. 5. Department of Pharmacy, King Saud Medical City, Riyadh, Saudi Arabia. 6. University of Copenhagen, Copenhagen, Denmark. 7. Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 8. Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. 9. Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
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 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.
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.
Authors: Natalija Karabasevic; Jason A Roberts; Luke Stronach; Saiyuri Naicker; Steven C Wallis; Fredrik Sjövall; Fekade Sime Journal: Antimicrob Agents Chemother Date: 2022-04-07 Impact factor: 5.938
Authors: Hanna E Sidjabat; Jolene Gien; David Kvaskoff; Keith Ashman; Kanchan Vaswani; Sarah Reed; Ross P McGeary; David L Paterson; Amanda Bordin; Gerhard Schenk Journal: Sci Rep Date: 2018-03-01 Impact factor: 4.379
Authors: Abdullah Alsultan; Shereen A Dasuqi; Fadi Aljamaan; Rasha A Omran; Saeed Ali Syed; Turki AlJaloud; Abdullah AlAhmadi; Saeed Alqahtani; Mohammed A Hamad Journal: Saudi Pharm J Date: 2021-10-08 Impact factor: 4.330