Implications of Vancomycin Troughs Drawn Earlier Than Current Guidelines
Vancomycin was isolated in the 1950s, but due to impurities causing adverse events and semisynthetic penicillin production, its use was greatly reduced.1,2 However, this medication gained in popularity 30 years later as a first-line treatment for methicillin-resistant Staphylococcus aureus infections.
In 2009 the Infectious Diseases Society of America (IDSA), American Society of Health System Pharmacists, and Society of Infectious Diseases Pharmacists developed a consensus review of the therapeutic monitoring and dosing of vancomycin in adult patients.3 Trough serum concentration levels are recommended as the most accurate and convenient method to monitor vancomycin. Per IDSA guidelines, an optimal trough is intended to be high enough to clear infections (> 10 mg/L) and prevent the development of vancomycin intermediate and resistant bacteria. Troughs should be obtained just before the next dose in steady-state conditions (starting just before the fourth dose) in patients with normal renal function.
Since the development of these guidelines, vancomycin trough levels are often drawn early.4-7 This may lead to an overestimation of the true trough concentration. A study by Morrison and colleagues in Boston, Massachusetts, found that 41.3% of vancomycin troughs were drawn early, and this resulted in statistically significant increases in the vancomycin concentrations, the rate of vancomycin regimen adjustments (decrease, discontinuation, or holding of dose), and the repeat vancomycin level orders compared with correctly timed troughs.5 It was noted by the study authors that lowering the daily dose of vancomycin based on early trough levels could lead to an underdosing of vancomycin and an increase in intermediate or resistant bacteria.
Related: IDWEEK: Antibiotic ‘time-out’ cut vancomycin use
The prevalence and implications of early trough samples have been measured at only 1 facility, and it is unknown whether these data can be reproduced elsewhere.5 Thus, this study sought to determine the prevalence and corresponding clinical actions of early trough levels at the Captain James A. Lovell Federal Health Care Center (JALFHCC). This is a unique facility that in 2010 combined a VA hospital with a DoD hospital. This facility cares for 67,000 military and retiree beneficiaries each year from southwestern Wisconsin and northwestern Illinois.The primary objective of this study was to measure the rate of early troughs drawn and their resultant effect on vancomycin regimens compared with correctly timed troughs. Secondarily, this study sought to compare the rate of repeated vancomycin trough levels in early vs correctly timed measurements.
Methods
This retrospective cohort analysis compared the outcomes of early and correctly timed vancomycin troughs. This study was approved by the Edward Hines, Jr. VA Hospital and JALFHCC Institutional Review Board. Veteran patients aged ≥ 18 years, hospitalized at JALFHCC, and receiving IV vancomycin at dosing intervals of 8, 12, 24, and 48 hours with measured trough levels between July 1, 2009, and July 1, 2013, were included in this study. Patients were excluded from analysis if vancomycin was given at any schedule other than the previously stated frequencies, they received hemodialysis during the treatment period, or their insurance coverage was through TRICARE (these patients had either active-duty or retired active-duty status).
Potentially eligible patients were identified via a Computerized Patient Records System (CPRS) search for laboratory vancomycin level measurements. The search supplied the researcher with the patient name, vancomycin level date and time, type of vancomycin level (trough or random), and vancomycin concentration. With this information, further data were gathered through CPRS: demographics, type of clinical infection, desired trough level (inferred if not listed in CPRS note), and vancomycin administration time (through the bar code medication administration system [BCMA] in CPRS). This analysis was of troughs, and multiple troughs may have originated from the same patient.
An early trough was defined as a trough taken more than 2 hours earlier than the next theoretical administration time or anytime before the third dose. After a trough was determined to be early or on time, the clinical actions taken during the dosing interval following sample collection were documented. A dose was considered to be held if stated in the BCMA or in a CPRS provider note. A dose was considered to be decreased with a change in frequency or strength that resulted in an overall daily dose decrease. A recollected vancomycin trough was counted within 24 hours of the trough or per a note in CPRS. Finally, observations that noted trends in vancomycin trough management were recorded.
The chi-square test with a significance criterion of 0.05 was used to compare early and on time troughs. Based on the results from the Boston, Massachusetts, study and 1 other study, about 780 vancomycin troughs would be required to meet significance in the primary outcome.5,6
