Adherence to guidelines for therapeutic monitoring of glycopeptide and aminoglycoside antibiotics

Introduction Guidelines for therapeutic drug monitoring (TDM) have been established for glycopeptide and aminoglycoside antibiotics due to their narrow therapeutic windows to ensure therapeutic efficacy and to avoid toxic overdosing with nephro- or ototoxicity. The purpose of this quality control study was to determine the adherence to TDM guidelines for the aminoglycoside gentamicin (G) and the glycopeptides vancomycin (V) and teicoplanin (T) in order to assess the need for improvements. Methods We included all inpatients admitted to the University Hospital Zurich over a 3-year-period from 01/01/2012 to 31/12/2014. All electronic orders of intravenously administered G, V, and T and the corresponding TDM-lab-orders were analyzed retrospectively. Medication orders during intensive care stays were not electronically available and were therefore excluded. Institutional guidelines released 2011 provided recommendations for initial monitoring no later than 72 h for G, 60 h for V and 96 h for T, respectively. Shorter initial TDM intervals have been advised for patients with impaired renal function and for thrice in contrast to once daily dosing of G. Guidelines released 2014 propose shorter intervals for G and T. In this analysis, however, these shortened intervals have not been considered. Drug therapies may be prescribed as single or multiple subsequent orders (e.g. for dose adjustments). Therefore, subsequent prescriptions being separated by ≤ 24h were considered as single continuous therapies. To analyze the adherence to guidelines we measured the time period between the start of drug therapy and the initial TDM. Results Drug therapies administered to 115’509 inpatients were analyzed, including 470 G therapies consisting of 1’045 orders, 2’396 V therapies with 6’168 orders and 807 T therapies with 2’184 orders. Therapies were administered for less than 72 h in 40% (188/470) of G, 41% (985/2’396) of V and 26% (209/807) of T. Therapies lasting ≥ 72 h were monitored according to guidelines for G in 72% (203/282), for V in 67% (939/1411) and for T in 63% (379/598). Therapies of ≥ 96 h, were monitored within 72 h for G in 74% (178/241), for V in 74% (907/1’224), and for T in 50% (275/552). Therapies of ≥ 120 h were not monitored at all for G in 7% (14/208), for V in 7% (68/1046), and for T in 13% (66/512), respectively. Conclusion Physicians’ adherence to TDM guidelines was only 72% or below, with the best compliance for G. Overall TDM adherence offers room for improvement and quality assurance actions have to be considered. Educational programs require a continuous effort. As a complementary measure computerized decision support might be implemented. Automated reminders could be displayed in the medical record whenever TDM is overdue. The same algorithms might also be applied to other therapies that have to be monitored according to guidelines. Studies are needed to evaluate the impact of these concepts on patients’ safety, treatment efficacy and physicians’ over-alerting.