Vancomycin therapeutic drug monitoring in paediatrics

Abstract

Aim: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. Methods: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. Results: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05-86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0-39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. Conclusion: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.

Are vancomycin dosing guidelines followed? A mixed methods study of vancomycin prescribing practices

“…A total of 1043 plasma vancomycin concentrations were collected; 939 (90%) during intermittent infusions and 104 (10%) during continuous infusions. A median (range) of 5 1–36 vancomycin concentrations were obtained in each course of therapy, collections occurring every 1.6 days (0.6–8 days).…”

“…Poorly timed sample collection is welldocumented in the clinical environment; only 20-59% of all TDM samples collected are trough concentrations. 8,12,16,32,33 Alternative approaches, such as Bayesian forecasting, that enable estimation of drug exposure from opportunistically collected samples are advocated, where available, to avoid misinterpretation of inappropriately timed collections, in addition to enabling optimal dosing. 34 Consistent with audits of other antimicrobials, 35 and perhaps most concerning, 44% of trough concentrations identified in the audit warranted dose adjustment according to guidelines, but were not acted upon.…”

“…However, only 14% of these were trough concentrations. Poorly timed sample collection is well‐documented in the clinical environment; only 20–59% of all TDM samples collected are trough concentrations 8,12,16,32,33 . Alternative approaches, such as Bayesian forecasting, that enable estimation of drug exposure from opportunistically collected samples are advocated, where available, to avoid misinterpretation of inappropriately timed collections, in addition to enabling optimal dosing 34 …”

Optimal exposure targets for vancomycin in the treatment of neonatal coagulase-negative Staphylococcus infection: A retrospective study based on electronic medical records

“…8 The vancomycin TDM guidelines issued by the Infectious Diseases Society of America (IDSA) in 2011 suggest that the serum trough concentration can be used as a surrogate indicator of the area under the curve (AUC). 9 After extensive research and use, and considering the potential inconsistency between the trough concentration of vancomycin and AUC, 10,11 as well as the improved results observed by monitoring the ratio of AUC over 24 h to the minimum inhibitory concentration (MIC), that is, the AUC/MIC in adults, 12,13 the IDSA revised guidelines in 2020 to recommend AUC/MIC > 400 and AUC < 600 mg h/L as the monitoring targets instead of the trough concentration. 14 Although these recommendations are mainly based on research data in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, they have been misused in vancomycin-related clinical practices.…”

Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit

“…Targeting trough concentrations > 15 μg/ml would lead to overshooting the target AUC 0–24 h above 400 and increased the risk of nephrotoxicity and other adverse events ( 22 , 23 ). Furthermore, the correlation between the vancomycin dose given and the ideal trough concentration achieved was poor ( 27 ). In the nephrotoxic group in our study, trough concentrations were 16.41 (11.59, 34.24) mg/L at a median dose of 40 mg/kg d, while the AUC 0–24 was as high as 763.24 (464.81, 1297.89).…”