scholarly journals Antibiotic dosing in critically ill patients with septic shock and on continuous renal replacement therapy: can we resolve this problem with pharmacokinetic studies and dosing guidelines?

Critical Care ◽  
2014 ◽  
Vol 18 (3) ◽  
pp. 156 ◽  
Author(s):  
Jason A Roberts ◽  
Darren M Roberts
Critical Care ◽  
2014 ◽  
Vol 18 (3) ◽  
pp. 227 ◽  
Author(s):  
Marta Ulldemolins ◽  
Sergi Vaquer ◽  
Mireia Llauradó-Serra ◽  
Caridad Pontes ◽  
Gonzalo Calvo ◽  
...  

2019 ◽  
Vol 54 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Brian M. Hoff ◽  
Jenana H. Maker ◽  
William E. Dager ◽  
Brett H. Heintz

Objective: To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. Data Sources: A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. Study Selection and Data Extraction: All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Data Synthesis: Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. Relevance to Patient Care and Clinical Practice: This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Conclusions: Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient’s needs.


2015 ◽  
Vol 59 (9) ◽  
pp. 5520-5528 ◽  
Author(s):  
Marta Ulldemolins ◽  
Dolors Soy ◽  
Mireia Llaurado-Serra ◽  
Sergi Vaquer ◽  
Pedro Castro ◽  
...  

ABSTRACTMeropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) andV= 33.00 · (weight/73)2.07, where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), andVis the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu) of drug above the MIC of the bacteria for 40% of dosing intervalT(referred to as 40% of the ƒuT>MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒuT>MICwas chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and inexpensive tool to help with titration of the meropenem dose and infusion time in this challenging population.


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