Trang T P H, Kessels R, Decroo T, Van Rie A
Department of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
IJTLD Open. 2024 Sep 1;1(9):384-390. doi: 10.5588/ijtldopen.24.0362. eCollection 2024 Sep.
Accurate diagnosis of bedaquiline (BDQ) resistance remains challenging. A Bayesian approach expresses this uncertainty as a probability of BDQ resistance (prBDQ) with a 95% credible interval. We investigated how prBDQ information influences BDQ prescribing decisions.
We performed a discrete choice experiment with 55 international rifampicin-resistant tuberculosis physicians. We employed mixed-effects multinomial logistic regression to quantify the effect of prBDQ, patient attributes, and contextual factors on the decision to continue BDQ or not when sequencing results become available.
PrBDQ was the most influential factor for BDQ decision-making, three times greater than treatment response. Each percentage point increase in prBDQ resulted in 8.2% lower odds (OR 0.92, 95% CI 0.90-0.93) of continuing BDQ as a fully effective drug and 5.0% lower odds (OR 0.95, 95% CI 0.94-0.96) of continuing it but not counting it as an effective drug. The most favourable patient profile for prescribing BDQ as a fully effective drug was a patient receiving the BPaLM regimen (BDQ, pretomanid, linezolid and moxifloxacin) with low prBDQ, good 1-month treatment response, fluoroquinolone-susceptible TB, and no prior BDQ treatment. Physicians with higher discomfort with uncertainty and more years of experience with BDQ were more inclined to stop BDQ.
Given the uncertainty of genotype-phenotype associations, physicians valued prBDQ for BDQ decision-making in rifampicin-resistant TB treatment.
准确诊断贝达喹啉（BDQ）耐药性仍然具有挑战性。贝叶斯方法将这种不确定性表示为BDQ耐药概率（prBDQ）及95%可信区间。我们研究了prBDQ信息如何影响BDQ的处方决策。
我们对55名国际耐利福平结核病医生进行了离散选择实验。我们采用混合效应多项逻辑回归来量化prBDQ、患者属性和背景因素对测序结果出来后继续使用或停用BDQ决策的影响。
prBDQ是BDQ决策中最具影响力的因素，其影响力是治疗反应的三倍。prBDQ每增加一个百分点，将BDQ作为完全有效药物继续使用的几率降低8.2%（比值比[OR]0.92，95%可信区间0.90 - 0.93），将其作为非有效药物继续使用的几率降低5.0%（OR 0.95，95%可信区间0.94 - 0.96）。将BDQ作为完全有效药物处方的最有利患者特征是接受BPaLM方案（BDQ、普瑞玛尼、利奈唑胺和莫西沙星）的患者，其prBDQ较低、1个月治疗反应良好、对氟喹诺酮敏感的结核病且既往未接受过BDQ治疗。对不确定性不适感较高且有更多BDQ使用经验的医生更倾向于停用BDQ。
鉴于基因型 - 表型关联的不确定性，医生在耐利福平结核病治疗的BDQ决策中重视prBDQ。
