Does On-Site Analysis of Serum Levels Optimise Management of Patients Taking Voriconazole? A Retrospective Cohort Study

Voriconazole is used for treatment and pre-emptive treatment of invasive fungal infections. TDM is widely used but literature and practice vary as to its utility and target levels. Recently serum voriconazole levels (sVRZ) have been performed on-site (LC-MS/MS assay) giving reduced turnaround time. We examined the impact of this on the clinical management of patients. The primary outcomes were the difference in % time in therapeutic range (%TTR) and latency to therapeutic range (LTR) between the on-site analysis group (06/ 11/14 - 06/11/15) and off site group (06/01/13 - 06/01/14) Secondary outcome was the clinical validation of our current therapeutic range (1.3-5.7 mg/L). A retrospective cohort study of all eligible post transplant patients was undertaken (4 heart and 33 lung). Data on indication, levels, co-morbidities, dose adjustments, adverse effects (ADRs) and outcomes of treatment were collected. 10 patients had invasive fungal infections (4 hearts and 6 lung), 27 received voriconazole for pre-emptive treatment. Median LTR was 10 days in the on-site analysis group compared with 94 days in the off site group. (P>0.05). Doses adjustments in response to sVRZ were seen in the invasive infections group. Mean %TTR (days) was 32% in the off-site and 54% group in the on-site group (p=0.08). Mean %TTR was found to be greater in those with confirmed infections (63%) when compared with those who received pre-emptive treatment (35%) (p=0.04). Treatment was successful in all patients. Many patients in the pre-emptive group consistently had sub therapeutic levels. One or more ADRs was recorded in 23 patients (62%), these required drug discontinuation in 13 patients. The median level at which treatment was stopped due to ADRs was 5.03 mg/L, (IQ range 3.77-6.66 mg/L) On site analysis of sVRZ has shortened LTR and increased TTR. This allows optimisation of patients with invasive infections. In the pre-emptive treatment group TDM was used to assign causality for ADRs with many patients having TDM at the time of stopping therapy. Most patients who had to stop due to ADRs were within the quoted therapeutic range. We will re-evaluate the existing TR for both groups in light of the findings that patients appear to respond well to treatment at levels currently considered sub-therapeutic, but suffer more ADRs in the upper range of the TR.