Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China
Yun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventr...
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Dove Medical Press
2024-12-01
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| Series: | Infection and Drug Resistance |
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| author | Wu Y Shi H Li W An Y Shao Y Rao X Waterfield NR Wang W Yang G |
| author_facet | Wu Y Shi H Li W An Y Shao Y Rao X Waterfield NR Wang W Yang G |
| author_sort | Wu Y |
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| description | Yun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventry, UK; 3Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yun Wu; Guowei Yang, Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10-63139853 ; +86-10-63139130, Email wuyun@ccmu.edu.com; yangguowei@hotmail.comPurpose: 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.Keywords: Pneumocystis jirovecii pneumonia, mutation, drug resistance, prognosis, non-HIV |
| format | Article |
| id | doaj-art-3bde4a1e716749ba8b883c1ccd8a2058 |
| institution | DOAJ |
| issn | 1178-6973 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Dove Medical Press |
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| series | Infection and Drug Resistance |
| spelling | doaj-art-3bde4a1e716749ba8b883c1ccd8a20582025-08-20T02:49:40ZengDove Medical PressInfection and Drug Resistance1178-69732024-12-01Volume 175619562798462Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in ChinaWu YShi HLi WAn YShao YRao XWaterfield NRWang WYang GYun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventry, UK; 3Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yun Wu; Guowei Yang, Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10-63139853 ; +86-10-63139130, Email wuyun@ccmu.edu.com; yangguowei@hotmail.comPurpose: 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.Keywords: Pneumocystis jirovecii pneumonia, mutation, drug resistance, prognosis, non-HIVhttps://www.dovepress.com/analysis-of-mutations-in-pneumocystis-jirovecii-dihydropteroate-syntha-peer-reviewed-fulltext-article-IDRpneumocystis jirovecii pneumoniamutationdrug resistanceprognosisnon-hiv |
| spellingShingle | Wu Y Shi H Li W An Y Shao Y Rao X Waterfield NR Wang W Yang G Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China Infection and Drug Resistance pneumocystis jirovecii pneumonia mutation drug resistance prognosis non-hiv |
| title | Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China |
| title_full | Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China |
| title_fullStr | Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China |
| title_full_unstemmed | Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China |
| title_short | Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China |
| title_sort | analysis of mutations in pneumocystis jirovecii dihydropteroate synthase and dihydropteroate reductase genes among non hiv patients in china |
| topic | pneumocystis jirovecii pneumonia mutation drug resistance prognosis non-hiv |
| url | https://www.dovepress.com/analysis-of-mutations-in-pneumocystis-jirovecii-dihydropteroate-syntha-peer-reviewed-fulltext-article-IDR |
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