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联合抗逆转录病毒治疗时代西班牙HIV感染患者的耶氏肺孢子菌肺炎:二氢蝶酸合酶突变的患病率及死亡预后因素

Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality.

作者信息

Alvarez-Martínez Míriam J, Moreno Asunción, Miró José M, Valls Maria Eugenia, Rivas Paula V, de Lazzari Elisa, Sued Omar, Benito Natividad, Domingo Pere, Ribera Esteban, Santín Miguel, Sirera Guillermo, Segura Ferràn, Vidal Francesc, Rodríguez Francisco, Riera Melchor, Cordero Maria Elisa, Arribas José Ramón, Jiménez de Anta Maria Teresa, Gatell José M, Wilson Paul E, Meshnick Steven R

机构信息

Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.

出版信息

Diagn Microbiol Infect Dis. 2008 Sep;62(1):34-43. doi: 10.1016/j.diagmicrobio.2008.04.016. Epub 2008 Jun 12.

DOI:10.1016/j.diagmicrobio.2008.04.016
PMID:18554841
Abstract

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

摘要

由于磺胺预防治疗和联合抗逆转录病毒疗法,HIV感染患者中耶氏肺孢子菌肺炎(PCP)的发病率有所下降。耶氏肺孢子菌二氢蝶酸合酶(DHPS)基因突变对生存率的影响存在争议,西班牙尚未有相关报道。这项前瞻性多中心研究纳入了2000年至2004年间207例患有PCP的HIV感染患者。对储存的标本进行了分子基因分型。使用逻辑回归模型确定了入住重症监护病房(ICU)和死亡的危险因素。7例患者(3.7%;95%置信区间[CI],1.5 - 7.5%)存在DHPS基因突变。总体死亡率为15%(95%CI,10 - 21%),在需要机械通气的患者中升至80%(95%CI,61 - 92%)。没有DHPS基因突变的患者死亡,也不需要入住ICU或进行机械通气。入院时PaO₂<60 mmHg是入住ICU的预测因素(P = 0.01),既往抗逆转录病毒治疗可预测不住入ICU(P = 0.009)。入院时PaO₂<60 mmHg和第1周内入住ICU是死亡的预测因素(分别为P = 0.03和P < 0.001)。西班牙DHPS基因突变的患病率较低,且与较差的预后无关。入院时严重呼吸衰竭是PCP预后的最强预测因素。

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