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Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity
Author(s) -
Benefield Russell J.,
Barker Brian C.,
Gast Christopher M.,
Alexander Donald P.
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1805
Subject(s) - nafcillin , medicine , creatinine , multivariate analysis , chemistry , antibiotics , penicillin , biochemistry
Objectives Primary objective: To retrospectively review nafcillin plasma concentrations (C NAF ) and determine nafcillin clearance (CL NAF ) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. Secondary objective: To identify clinical variables associated with CL NAF and nafcillin‐related adverse drug reactions ( ADR s). Methods Retrospective chart review of patients receiving nafcillin via continuous infusion at University of Utah Health Care from 2006 to 2013 who had at least one steady‐state C NAF measured. CL NAF was determined by dividing the nafcillin rate of infusion by C NAF . Adverse drug reactions (ADR s) were defined using the National Institutes of Health, Division of Microbiology and Infectious Diseases criteria and scored for probability of association with nafcillin by using Naranjo criteria. Multivariate models were constructed to identify independent variables associated with CL NAF and ADR s. Main results Seventy‐six C NAF from 54 patients were included. Median CL NAF was 13.9 L/hour (range ≤ 4.2 to 36.9 L/hr). Congestive heart failure (p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were associated with reduced CL NAF , and Hispanic race (p=0.002) was associated with increased CL NAF by multivariate analysis. Twenty patients (37.0%) experienced an ADR . C NAF were significantly higher between patients that experienced an ADR and those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADR s associated with C NAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0 vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate analysis identified C NAF as being independently associated with ADR s. A putative toxicity relationship between C NAF and predicted probability of ADR was established. Conclusions Several patient variables were associated with impaired CL NAF , and elevated C NAF were associated with ADR s. Additional studies assessing the utility of nafcillin therapeutic drug monitoring to minimize toxicity are warranted.