Why peak and trough vancomycin

Thus, we designed this study to determine how often specimen collections for vancomycin trough levels are incorrectly timed, to compare vancomycin concentrations between levels drawn too early and those correctly timed, and to examine differences between the 2 groups in the frequency that clinicians adjusted dosing and obtained repeat laboratory tests.

The BWH clinical chemistry laboratory performs approximately vancomycin assays every month. We performed a retrospective analysis of the clinical practice of vancomycin monitoring. As outlined in Figure 1 , we evaluated all vancomycin level determinations performed during the month study period of April 1, , to April 30, , that met inclusion criteria. The first criterion required that levels have a documented collection time.

Second, we only included levels for patients receiving vancomycin every 12 hours Q12H , the most common dosing interval at our institution. Vancomycin levels included in analysis. The process of selecting vancomycin levels to include in the study is shown. Our institution has an internally developed laboratory information system LIS that we accessed to obtain a record of all vancomycin measurements performed by the BWH clinical chemistry laboratory during the study period.

The time the employee badge is scanned is recorded as the drug administration time, which we used to assess level timing as described subsequently. In most cases, we considered the last dose to be the dose given before sample collection. We compared the plasma vancomycin concentrations and subsequent clinician actions in the 2 groups drawn too early vs correctly timed to investigate the possible adverse effects of drawing a sample too early.

We also determined whether the 2 groups had similar baseline characteristics age, sex, most recent creatinine level, estimated glomerular filtration rate, and previous vancomycin test result to verify that these characteristics were not contributing to any differences in the 2 populations.

For calculation purposes, all test results below the lower limit of detection of the assay 0. Clinical actions taken in response to levels were grouped into 3 types: 1 dose held, decreased, or discontinued; 2 dose increased; and 3 repeat vancomycin level. Only clinical actions performed within 12 hours of reporting the vancomycin level, but before another level was reported, were included in the study.

For cases in which no dosing adjustment was found, we determined whether a repeat vancomycin level, ie, an additional test reported within 24 hours of the original, had been performed.

A P value less than. Of 10, plasma vancomycin concentrations measured in the study period, we excluded 2, Of the In total, 2, Data for a total of 1, different patients were included in the study, of whom patients had multiple vancomycin levels included and had occasion to fall into both the correctly and incorrectly timed groups. There was no significant difference in age, sex, renal function, or previous vancomycin level between the 2 groups Table 1. Of the evaluated levels, The median sampling time relative to the last dose was 7.

Figure 3 shows the average vancomycin concentration for samples drawn at each hour after the last dose. The average concentration peaked at 2 to 3 hours at Levels drawn too early were twice as likely as correctly timed levels to be supratherapeutic Early levels accounted for Clinicians also more frequently obtained a repeat vancomycin level, as opposed to adjusting the dose when a level drawn too early was reported The absolute number of vancomycin levels and the percentage of total are shown for each hour.

Effect of sample timing on plasma vancomycin concentration. The average plasma vancomycin concentration is shown for samples obtained at each hour since the last vancomycin dose. We found that the samples for about 4 in 10 vancomycin levels intended to predict vancomycin efficacy in patients receiving Q12H dosing were collected too early and, thus, did not represent true trough levels.

When compared with correctly timed levels, samples drawn too early had significantly higher plasma vancomycin concentrations and were twice as likely to be supratherapeutic. In some cases, clinicians may have realized that levels were not drawn at the appropriate time, as suggested by a high number of repeat levels obtained, particularly for collections drawn 2 to 6 hours after the last dose. However, in many cases, it seems that clinicians may have not have realized that elevated concentrations were due to inaccurate timing.

In these cases, the inappropriate use of levels drawn too early to predict efficacy could have led to underdosing and therapeutic failure.

Once the root cause of inaccurate sample timing is established, a more robust infrastructure is required to increase the accuracy of collections for vancomycin levels. Clinicians often adjusted dosing after obtaining an incorrectly timed level Table 2 and Figure 4 , even though these levels did not represent true trough levels and, therefore, should not be used as a basis for clinical decisions.

Moreover, clinicians held, decreased, and discontinued vancomycin at a higher frequency when responding to early levels, particularly when levels were drawn at 8 to 10 hours after the last dose Figure 4A.

These levels, comprising While only a couple of hours off, these samples were still 1. Effect of sample timing on clinical actions. The percentage of vancomycin levels followed by a clinical decision to hold, decrease, or discontinue vancomycin dosing A , increase vancomycin dosing B , or not adjust dosing but obtain a repeat level C is shown for levels obtained at each hour since the last dose. In comparison, levels drawn less than 8 hours after the last dose, which were typically higher Figure 3 , were not as likely to be followed by dosing adjustments and more likely to be repeated Figure 4 , suggesting that clinicians sometimes questioned the accuracy of these results.

The pharmacists at our institution often intervene when levels are high, and they carefully consider pharmacokinetics, which may have contributed to awareness that these levels did not represent true troughs and which may explain the higher rate of repeats. At institutions with less active clinical pharmacy programs, such recoveries would be expected to be less frequent. However, even if clinicians are realizing the levels are inaccurately timed and thus refraining from inappropriate use of the levels, repeating laboratory tests contributes to delays in patient management and waste in the system.

We observed a low percentage of levels within the therapeutic range and a higher than expected percentage below the therapeutic range, even within the group of early levels Table 2 , which may explain the relatively high rates of dosing increases in both groups Figure 4B. These findings are consistent with previous findings at our institution, and a quality improvement project is currently underway in the pharmacy department to improve vancomycin dosing. The root cause for the high percentage of inappropriately timed levels is currently under investigation, but we suspect the cause is multifactorial.

While clinicians are prompted at the time of placing an electronic order for a vancomycin level with ordering instructions and recommendations, the menu option does not default to a trough level. After a clinician places an order, the nurse must schedule for the level to be drawn, sometimes requiring coordination with the phlebotomy team, which may further complicate the process of getting a correctly timed sample.

Finally, neither the sample collection time nor any dosing information is displayed with the vancomycin result in our LIS, making it difficult for clinicians to be cognizant of sample timing relative to dose administration and providing 1 explanation why inappropriate clinical actions were observed for early levels. The increased adoption of clinical information systems presents new opportunities to address the issue of correct timing of monitoring for vancomycin and other therapeutic drugs through real-time display of dose administration, specimen collection, and test result data, as well as automated guidance to help clinicians time samples correctly.

Of note, the method we used to gather data and evaluate the timing of specimen collection was automated and used data recorded by our LIS and eMAR. Our ongoing efforts are aimed at linking the LIS, positive patient identification system, and eMAR such that we can display the time relative to last administration along with each drug level. It is possible that some of the levels we evaluated were intended as peaks or random levels, although peaks are rarely clinically indicated, and we carefully designed criteria to exclude random levels.

We also did not evaluate whether trough levels were clinically appropriate eg, had the patient reached steady state. Furthermore, it is possible that clinical factors beyond timing of vancomycin levels contributed to some of our findings, although we did not observe any significant baseline differences in age, sex, renal function, or previous vancomycin levels between the 2 groups.

Samples for vancomycin trough levels were frequently drawn too early, resulting in higher vancomycin concentrations that may have contributed to a high rate of repeat vancomycin levels and possibly inadvertent underdosing.

Further effort is needed to identify the root causes of incorrect sample timing and to implement solutions to improve the accuracy of vancomycin monitoring. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p Exam is located at www. Moellering RC Jr. Vancomycin: a year reassessment. Clin Infect Dis. Google Scholar.

Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Griffith RS. Introduction to vancomycin. Rev Infect Dis. November—December ; 3 suppl : S — S Saunders NJ. Why monitor peak vancomycin concentrations? Levine DP. Vancomycin: a history. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.

Appropriateness of sampling times for therapeutic drug monitoring. Am J Hosp Pharm. Complicated infections require higher target levels, typically Peak concentrations do not correlate well to efficacy or nephrotoxicity, but may be useful for pharmacokinetic analyses eg, area under the curve: AUC studies or for select patients.

Trough levels correlate better with efficacy than peak levels, with target trough levels of As with any assay employing mouse antibodies, the possibility exists for interference by human antimouse antibodies HAMA in the sample, which could cause falsely lowered results.

Am J Health Syst Pharm. Mayo Clinic. Updated July 29, Skip to main content. Register Sign In. Test Catalog Account. Outreach Solutions Tactics Articles Events.