二氢蝶酸合酶 (DHPS) 突变可能与耶氏肺孢子菌肺炎 (PCP) 中甲氧苄氨嘧啶-磺胺甲恶唑耐药以及较差的临床结果相关。然而，非人类免疫缺陷病毒（HIV）感染者PCP中DHPS突变的临床意义仍不清楚。2016年至2020年间，回顾性纳入台湾三所三级转诊医院的PCP患者。对 DHPS 蛋白中的两个点突变 Thr55Ala 和 Pro57Ser 进行了分析。排除呼吸道标本中存在无效 DHPS 突变、慢性呼吸衰竭、接受气管插管手术干预、HIV 感染、耶氏肺孢子虫定植以及无乳酸脱氢酶 (LDH) 数据的患者。主要结果是30天生存率。总共分析了215名患者，在78名（36.3％）名患者中发现DHPS内部突变体，68名（31.6％）名患者在30天内死亡。共有 214 名患者 (99.5%) 接受甲氧苄啶-磺胺甲恶唑作为一线治疗。野生型和突变型 DHPS PCP 的机械通气率、30 天死亡率和院内死亡率相似。调整重要混杂因素后，LDH > 500 U/L（调整后风险比 [aHR] = 2.448，p = 0.001），肺炎严重程度指数 > 135 mg/dL（aHR = 1.689，p = 0.049），并且患有实体瘤（ aHR =1.832，p =0.034）与较高的死亡率独立相关。在亚组分析中，突变型 DHPS PCP 患者在 65 岁以上患者 (p = 0.049)、患有淋巴细胞减少症 (p = 0.040) 和无实体瘤患者 (p = 0.045) 的患者中，30 天死亡率较低。 PCP、DHPS 内的点突变体可能与甲氧苄啶-磺胺甲恶唑治疗结果无关。有必要进行进一步的前瞻性大规模研究。版权所有 © 2023。由 Elsevier Ltd 出版。

Dihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significances of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear.Between 2016 and 2020, PCP patients in three tertiary referral hospitals in Taiwan were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein, were analyzed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonization, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival.In total, 215 patients were analyzed, mutants inside DHPS were found in 78 (36.3 %) patients, and 68 (31.6 %) patients died within 30 days. A total of 214 (99.5%) patients received trimethoprim-sulfamethoxazole as the first line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality rates were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH >500 U/L (adjusted hazard ratio [aHR] =2.448, p =0.001), pneumonia severity index >135 mg/dL (aHR =1.689, p =0.049), and having solid tumors (aHR =1.832, p =0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients older than 65 years (p =0.049), with lymphopenia (p =0.040) and those without solid tumor (p =0.045).In non-HIV-infected PCP, point mutants inside DHPS may not associate with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.Copyright © 2023. Published by Elsevier Ltd.