METHODS: The study was conducted in 2 parts: (1) we sent a survey to a panel of international experts of VAs asking about their use of pneumocystis prophylaxis drugs and (2) we performed a systematic review of the literature of all published cases of patients receiving these drugs for VA to estimate the prevalence of PJP in this population.
RESULTS: Answers from 68 experts were analyzed: 21 (30.9%) answered they always add PJP prophylaxis when prescribing mTOR inhibitors, 20 (29.4%) case-by-case, and 27 (39.7%) never. For the systematic review, among 3,053 reports screened, 217 were included involving 1,189 patients (1,143 received sirolimus, 38 everolimus, 4 alpelisib, 4 miransertib). Among the 1,189 cases, 2 (0.2%) PJP were reported: one under sirolimus and one under everolimus. Thus, the prevalence of PJP was estimated at 0.88 cases/1,000 patients under sirolimus (95% CI: -0.84 to 2.59) and 26.31 cases/1,000 under everolimus (95% CI: -24.58 to 77.18). Patients with PJP never received prophylaxis drugs. We found no PJP cases under alpelisib and miransertib. PJP prophylaxis was given in 218 (18.3%) cases, more frequently for children (91.3 vs. 77.2% in the non-prophylaxis group, p = 0.012), mostly trimethoprim-sulfamethoxazole (186 patients, 85.3%).
CONCLUSIONS: Our study shows that even if PJP is a rare event, it may occur in patients with VAs treated with an mTOR inhibitor. Although our results cannot allow for revising guidelines, prophylaxis with TMP-SMX might be appropriate for a subgroup of patients with risk factors for PJP.
方法:该研究分为两个部分:(1)我们向VAs的国际专家小组发送了一项调查,询问他们使用肺孢子虫预防药物的情况;(2)我们对所有已发表的接受这些药物治疗VA的患者的文献进行了系统回顾,以估计该人群中PJP的患病率。
结果:分析了来自68位专家的答案:21位(30.9%)回答说,他们在处方mTOR抑制剂时总是添加PJP预防,20例(29.4%),和27(39.7%)从未。对于系统审查,在筛选的3053份报告中,包括217名患者,涉及1189名患者(1143名患者接受了西罗莫司,38依维莫司,4alpelisib,4miransertib)。在1189起案件中,2(0.2%)PJP被报道:一个在西罗莫司和一个在依维莫司。因此,在西罗莫司治疗下,PJP的患病率估计为0.88例/1,000例(95%CI:-0.84~2.59),在依维莫司治疗下,PJP的患病率估计为26.31例/1,000例(95%CI:-24.58~77.18).PJP患者从未接受过预防药物。我们没有发现alpelisib和miransertib下的PJP病例。在218例(18.3%)病例中进行了PJP预防,更常见的儿童(91.3vs.非预防组77.2%,p=0.012),主要是甲氧苄啶-磺胺甲恶唑(186名患者,85.3%)。
结论:我们的研究表明,即使PJP是罕见事件,它可能发生在接受mTOR抑制剂治疗的VAs患者中。虽然我们的结果不能允许修改指导方针,TMP-SMX预防可能适用于有PJP危险因素的患者亚组.