Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.

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A Monte Carlo Simulation Approach for Beta-Lactam Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

The Journal of Clinical Pharmacology ◽

10.1002/jcph.1137 ◽

2018 ◽

Vol 58 (10) ◽

pp. 1254-1265 ◽

Cited By ~ 5

Author(s):

Soo Min Jang ◽

Katherine N. Gharibian ◽

Susan J. Lewis ◽

William H. Fissell ◽

Ashita J. Tolwani ◽

...

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Simulation Approach ◽

Beta Lactam ◽

Intermittent Renal Replacement Therapy

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Development of a vancomycin dosing approach for critically ill patients receiving hybrid hemodialysis using Monte Carlo simulation

SAGE Open Medicine ◽

10.1177/2050312118773257 ◽

2018 ◽

Vol 6 ◽

pp. 205031211877325 ◽

Cited By ~ 7

Author(s):

Susan J Lewis ◽

Bruce A Mueller

Keyword(s):

Monte Carlo ◽

Renal Replacement Therapy ◽

Serum Concentration ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Vancomycin Dose ◽

The Third ◽

Dosing Nomogram ◽

Intermittent Renal Replacement Therapy

Objectives: Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Methods: Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted “in silico” vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC24h) of 400–700 mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. Results: An initial vancomycin dose of 15 or 20 mg/kg immediately followed by 15 mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC24h of ≥400 mg·h/L for ≥90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC24h of ≥700 mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%–88% of patients achieved AUC24h of 400–700 mg·h/L. Conclusion: An initial loading dose of 15–20 mg/kg followed by a maintenance regimen of 15 mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.

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Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update

Annals of Pharmacotherapy ◽

10.1177/1060028019865873 ◽

2019 ◽

Vol 54 (1) ◽

pp. 43-55 ◽

Cited By ~ 12

Author(s):

Brian M. Hoff ◽

Jenana H. Maker ◽

William E. Dager ◽

Brett H. Heintz

Keyword(s):

Renal Function ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Response To Therapy ◽

Intermittent Hemodialysis ◽

Intermittent Renal Replacement Therapy ◽

Antibiotic Dosing

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.

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