METHODS AND ANALYSIS: A three-step approach consensus approach will be adopted for this study for the development of a validated medical curriculum guideline on AMR. A preliminary curriculum for the programme will be drafted from reviews of published literature including syllabi as well as national and international guidelines. A total of 26 potential sources were found to be relevant, and selected for this study. Subsequently, the drafted curriculum will be subjected for validation via online surveys by various infectious disease experts. Finally, a Delphi technique will be employed to obtain consensus on heterogeneous findings to the revised curriculum. The quantitative and qualitative responses will be analysed and discussed among the panel of researchers.
ETHICS AND DISSEMINATION: This study protocol has been approved by the Institute of Health Sciences Research Ethics Committee of Universiti Brunei Darussalam (Reference: UBD/PAPRSBIHSREC/2020/124). Informed consent declaration will be collected prior to data collections as indication of agreement of participation in the study. Results will be made available to medical educators and also researchers on AMR and stewardship. The results also will be disseminated at feedback sessions to officers at Ministry of Health and Ministry of Education, Brunei Darussalam.
METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.
RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.
CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.