Frazee, Erin N

Clinical studies have reported additive nephrotoxicity associated with the combination of vancomycin (VAN) and piperacillin-tazobactam (TZP). This study assessed differences in glomerular filtration rate (GFR) and urinary biomarkers between rats receiving VAN and those receiving VAN + TZP.

Background: Goals of managing patients with acute kidney injury (AKI) are mitigating disease progression and ensuring safety while providing supportive care because no effective treatment exists. One strategy recommended in guidelines to meet these goals is optimizing medication management. Unfortunately, guideline implementation appears to be lacking as observed by the frequent occurrence of medication errors and adverse drug events. Objective: To address this performance gap in the care of hospitalized patients receiving nephrotoxins and renally eliminated drugs, we sought to provide a potential intervention based on theory-informed behavior change. Methods: Formative research with a qualitative analysis identifying what needs to change in patient care was completed by obtaining clinician opinion and expert opinion and reviewing the published literature. Frontline providers, including 8 physicians, 4 pharmacists, and a multiprofessional group of authors, provided insight into possible barriers to appropriate prescribing. Capability, Opportunity, Motivation and Behavior model and Theoretical Domain Framework were applied to characterize behavior change interventions and inform a potential implementation intervention for changing inappropriate prescribing behaviors. Results: Lack of knowledge about appropriate drug management in patients at risk for adverse outcomes was provided as a major barrier. Other reported barriers included a lack of: (1) tools to assist with drug management, (2) motivation to make changes, (3) routinization, and (4) an accountable clinician. Conclusions and Relevance: Assigning a designated clinician to execute a stepwise, routine care process following the checklist provided is a recommended intervention to overcome barriers. The intended impact is behavior change that reduces inappropriate prescribing.

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function.

The advent of immunotherapy has improved outcomes of patients in a number of cancers. 1 While immunotherapy helps the immune system recognize malignant cells, it also can lead to adverse effects that mimic autoimmune diseases including, but not limited to, rash, colitis, pneumonitis, and nephritis. Diagnosis of immunotherapy related nephritis is based on serum creatinine trends, which can be falsely elevated in the setting of high muscle mass. Cystatin C is an adjunctive kidney biomarker that can estimate glomerular filtration rate independent of muscle mass. We present a case where the use of cystatin C avoided unnecessary therapy interruption in a young, athletic man being treated with nivolumab for melanoma. Further research is needed to define the role cystatin C in monitoring kidney function during immunotherapy.

Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.