Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

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Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-22.1.69 ◽

2017 ◽

Vol 22 (1) ◽

pp. 69-73

Author(s):

Jeffrey J. Cies ◽

Wayne S. Moore ◽

Susan B. Conley ◽

Paul Shea ◽

Adela Enache ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Therapeutic Drug Monitoring ◽

Continuous Renal Replacement Therapy ◽

Continuous Infusion ◽

Replacement Therapy ◽

Drug Monitoring ◽

Severe Combined Immunodeficiency ◽

Elevated Serum ◽

Therapeutic Drug ◽

Pharmacokinetic Data

An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0.68 mg/dL, an increase from the baseline of 0.28 mg/dL. On day 9, the patient was initiated on continuous renal replacement therapy (CRRT) and the doripenem dosing was changed to a continuous infusion of 2.5 mg/kg/hr (60 mg/kg/day). Approximately 12.5 hours after the start of the doripenem a serum concentration was obtained, which was 4.01 mg/L corresponding to a clearance of 10.5 mL/min/kg. The pediatric dosing and pharmacokinetic data available for doripenem suggest a clearance estimate of 4.4 to 4.8 mL/min/kg, and the adult clearance estimate is 2.4 to 3.78 mL/min/kg. The calculated clearance in our patient of 10.5 mL/min/kg is over double the highest clearance estimate in the pediatric literature. This case demonstrates that doripenem clearance is significantly increased with CRRT in comparison with the published pediatric and adult data. An appropriate pharmacodynamic outcome (time that free drug concentration > minimum inhibitory concentration) can be achieved by continuous infusion doripenem with concurrent therapeutic drug monitoring.

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Impact of β-lactam antibiotic therapeutic drug monitoring on dose adjustments in critically ill patients undergoing continuous renal replacement therapy

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2017.01.009 ◽

2017 ◽

Vol 49 (5) ◽

pp. 589-594 ◽

Cited By ~ 21

Author(s):

Caleb J.P. Economou ◽

Gloria Wong ◽

Brett McWhinney ◽

Jacobus P.J. Ungerer ◽

Jeffrey Lipman ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Therapeutic Drug Monitoring ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Lactam Antibiotic

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Lacosamide Pharmacokinetics in a Critically Ill Patient During Continuous Renal Replacement Therapy

Journal of Pharmacy Practice ◽

10.1177/0897190018803765 ◽

2018 ◽

Vol 33 (3) ◽

pp. 395-398 ◽

Cited By ~ 1

Author(s):

Patrick M. Wieruszewski ◽

Arnaldo Lopez-Ruiz ◽

Robert C. Albright ◽

Jennifer E. Fugate ◽

Erin Frazee Barreto

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Drug Exposure ◽

Critically Ill Patient ◽

Therapeutic Drug ◽

Intermittent Hemodialysis ◽

Pharmacokinetic Studies ◽

Extracorporeal Removal

The objective of this study is to describe the pharmacokinetics of lacosamide in a critically ill adult during continuous venovenous hemofiltration (CVVH). A 78-year-old male developed sepsis and acute kidney injury following cardiac surgery. He was initially treated with intermittent hemodialysis but developed nonconvulsive status epilepticus at the end of the first session and was subsequently initiated on CVVH. In addition to lorazepam boluses, levetiracetam, and midazolam infusion, he was loaded with lacosamide 400 mg intravenously and started on 200 mg intravenously twice daily as maintenance therapy. Noncompartmental modeling of lacosamide pharmacokinetics revealed significant extracorporeal removal, a volume of distribution of 0.69 L/kg, elimination half-life of 13.6 hours, and peak and trough concentrations of 7.4 and 3.7 mg/L, respectively (goal trough, 5-10 mg/L). We found significant extracorporeal removal of serum lacosamide during CVVH, which was higher than previously reported. This led to subtherapeutic concentrations and decreased overall antiepileptic drug exposure. The relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations.

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Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽

10.1186/s13054-020-03397-1 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Dennis Kühn ◽

Carlos Metz ◽

Frederik Seiler ◽

Holger Wehrfritz ◽

Sophie Roth ◽

...

Keyword(s):

Intensive Care ◽

Renal Replacement Therapy ◽

Therapeutic Drug Monitoring ◽

Extracorporeal Membrane Oxygenation ◽

Replacement Therapy ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Serum Concentrations ◽

Icu Patients ◽

Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

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Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Pharmacy ◽

10.3390/pharmacy8010018 ◽

2020 ◽

Vol 8 (1) ◽

pp. 18 ◽

Cited By ~ 1

Author(s):

Soo Min Jang ◽

Sergio Infante ◽

Amir Abdi Pour

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Patient Specific ◽

Therapeutic Drug ◽

Intermittent Hemodialysis ◽

Drug Dosing ◽

Low Efficiency

Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

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