Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients
Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients
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DOI：
10.1086/315719
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发表时间：
2000-08-01
影响因子：
6.4
通讯作者：
Meshnick, SR
中科院分区：
文献类型：
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作者：
Kazanjian, P;Armstrong, W;Meshnick, SR
本研究旨在确定AIDS合并卡氏肺孢子虫肺炎（PCP）患者的卡氏肺孢子虫二氢蝶酸合酶（DHPS）基因突变是否受磺胺或砜预防治疗持续时间的影响，以及是否影响对磺胺或砜治疗的反应。从1991年至1999年来自4个医疗中心的97例AIDS PCP患者中，采用聚合酶链反应（PCR）扩增卡氏肺孢子虫DHPS基因，并进行测序。在暴露于磺胺或砜预防的患者的分离株中观察到76%的突变，而在未暴露的患者的分离株中观察到23%的突变（P = 0.001）。预防的持续时间增加了突变的风险（每个暴露月的相对风险[RR]为1.06; P = .02），28%的突变患者磺胺或砜治疗失败;突变增加了磺胺或砜治疗失败的风险（RR，2.1; P = 0.01），因此，磺胺或砜预防的持续时间增加了发生卡氏肺孢子虫突变的机会。大多数突变患者对磺胺或砜治疗有反应。
This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced, Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P = .001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P = .02), Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P = 0.01), Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.