Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China.

IF 2.9 3区医学 Q2 INFECTIOUS DISEASES

Infection and Drug Resistance Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI:10.2147/IDR.S491478

Yun Wu, Huixin Shi, Wei Li, Yijun An, Yuhan Shao, Xia Rao, Nicholas R Waterfield, Wei Wang, Guowei Yang

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引用次数: 0

Abstract

Purpose: Pneumocystis jirovecii pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on P. jirovecii drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii in non-HIV patients in China, providing a reference for drug usage.

Methods: We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including P. jirovecii infection (n = 14) and P. jirovecii colonization (n = 31). This analysis also considered clinical characteristics, P. jirovecii burden, treatment response, and prognosis.

Results: Compared to the P. jirovecii colonization, P. jirovecii infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, P<0.05) with higher P. jirovecii burden (P<0.05) and worse prognosis (P<0.05). Additionally, patients with P. jirovecii infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.

Conclusion: Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.

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中国非hiv感染者肺囊虫二氢蝶呤合成酶和二氢蝶呤还原酶基因突变分析。

目的：吉氏肺囊虫肺炎（PJP）在非hiv患者中具有很高的致死率。然而，在这些患者中，关于p.j roveci耐药相关基因突变的数据有限。本研究旨在了解中国非hiv患者中吉氏疟原虫二氢叶酸还原酶（DHFR）和二氢叶酸合酶（DHPS）基因突变的流行情况，为用药提供参考。方法：对中国45例非hiv患者DHPS和DHFR基因多态性进行分析，包括14例感染和31例定植。该分析还考虑了临床特征、氏弓形虫负担、治疗反应和预后。结果：与定殖相比，感染耶氏弓形虫后血液指标（GR%、LY%、HGB、TP、ALB、CRP、pp、pp）和耶氏弓形虫负担（PPP）显著改变。感染耶氏螨者更易感染eb病毒、巨细胞病毒、支原体和肺炎克雷伯菌等感染。虽然在本研究中没有发现DHPS基因中已知的耐药突变，但发现了10个非同义突变。此外，在DHFR基因中发现了10个非同义突变和2个同义突变。然而，这些突变与较差的预后无关。结论：我们的研究结果表明，在中国非hiv高危患者中，仍推荐使用TMP-SMX预防PJP。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection and Drug Resistance Medicine-Pharmacology (medical)

CiteScore

5.60

自引率

7.70%

发文量

826

审稿时长

16 weeks

期刊介绍： About Journal Editors Peer Reviewers Articles Article Publishing Charges Aims and Scope Call For Papers ISSN: 1178-6973 Editor-in-Chief: Professor Suresh Antony An international, peer-reviewed, open access journal that focuses on the optimal treatment of infection (bacterial, fungal and viral) and the development and institution of preventative strategies to minimize the development and spread of resistance.