High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy
Main Author: | |
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Publication Date: | 2017 |
Other Authors: | , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | https://doi.org/10.1128/AAC.01290-16 |
Summary: | Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP. |
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High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapyDHPSDihydropteroate synthasePneumocystis jiroveciiSulfa drugsSulfa resistanceSulfamethoxazole trimethoprimPharmacologyPharmacology (medical)Infectious DiseasesBiochemistry, Genetics and Molecular Biology (miscellaneous)SDG 3 - Good Health and Well-beingMutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.Instituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)RUNPonce, Carolina A.Chabé, MagaliGeorge, ClaudioCárdenas, AlejandraDurán, LuisaGuerrero, JuliaBustamante, RebecaMatos, OlgaHuang, LaurenceMiller, Robert F.Vargas, Sergio L.2018-05-10T22:12:37Z2017-02-012017-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttps://doi.org/10.1128/AAC.01290-16eng0066-4804PURE: 2451123http://www.scopus.com/inward/record.url?scp=85010972039&partnerID=8YFLogxKhttps://doi.org/10.1128/AAC.01290-16info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:19:49Zoai:run.unl.pt:10362/36434Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:28.748095Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
title |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
spellingShingle |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy Ponce, Carolina A. DHPS Dihydropteroate synthase Pneumocystis jirovecii Sulfa drugs Sulfa resistance Sulfamethoxazole trimethoprim Pharmacology Pharmacology (medical) Infectious Diseases Biochemistry, Genetics and Molecular Biology (miscellaneous) SDG 3 - Good Health and Well-being |
title_short |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
title_full |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
title_fullStr |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
title_full_unstemmed |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
title_sort |
High prevalence of Pneumocystis jirovecii dihydropteroate synthase gene mutations in patients with a first episode of Pneumocystis pneumonia in Santiago, Chile, and clinical response to trimethoprim-sulfamethoxazole therapy |
author |
Ponce, Carolina A. |
author_facet |
Ponce, Carolina A. Chabé, Magali George, Claudio Cárdenas, Alejandra Durán, Luisa Guerrero, Julia Bustamante, Rebeca Matos, Olga Huang, Laurence Miller, Robert F. Vargas, Sergio L. |
author_role |
author |
author2 |
Chabé, Magali George, Claudio Cárdenas, Alejandra Durán, Luisa Guerrero, Julia Bustamante, Rebeca Matos, Olga Huang, Laurence Miller, Robert F. Vargas, Sergio L. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) RUN |
dc.contributor.author.fl_str_mv |
Ponce, Carolina A. Chabé, Magali George, Claudio Cárdenas, Alejandra Durán, Luisa Guerrero, Julia Bustamante, Rebeca Matos, Olga Huang, Laurence Miller, Robert F. Vargas, Sergio L. |
dc.subject.por.fl_str_mv |
DHPS Dihydropteroate synthase Pneumocystis jirovecii Sulfa drugs Sulfa resistance Sulfamethoxazole trimethoprim Pharmacology Pharmacology (medical) Infectious Diseases Biochemistry, Genetics and Molecular Biology (miscellaneous) SDG 3 - Good Health and Well-being |
topic |
DHPS Dihydropteroate synthase Pneumocystis jirovecii Sulfa drugs Sulfa resistance Sulfamethoxazole trimethoprim Pharmacology Pharmacology (medical) Infectious Diseases Biochemistry, Genetics and Molecular Biology (miscellaneous) SDG 3 - Good Health and Well-being |
description |
Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02-01 2017-02-01T00:00:00Z 2018-05-10T22:12:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1128/AAC.01290-16 |
url |
https://doi.org/10.1128/AAC.01290-16 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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0066-4804 PURE: 2451123 http://www.scopus.com/inward/record.url?scp=85010972039&partnerID=8YFLogxK https://doi.org/10.1128/AAC.01290-16 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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10 application/pdf |
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