scholarly journals High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa

2010 ◽  
Vol 48 (6) ◽  
pp. 2016-2021 ◽  
Author(s):  
L. Dini ◽  
M. du Plessis ◽  
J. Frean ◽  
V. Fernandez
2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Carolina A. Ponce ◽  
Magali Chabé ◽  
Claudio George ◽  
Alejandra Cárdenas ◽  
Luisa Durán ◽  
...  

ABSTRACT 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.


PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49991 ◽  
Author(s):  
Steve M. Taylor ◽  
Steven R. Meshnick ◽  
William Worodria ◽  
Alfred Andama ◽  
Adithya Cattamanchi ◽  
...  

AIDS ◽  
2005 ◽  
Vol 19 (8) ◽  
pp. 801-805 ◽  
Author(s):  
Kristina Crothers ◽  
Charles B Beard ◽  
Joan Turner ◽  
Gena Groner ◽  
Melissa Fox ◽  
...  

2005 ◽  
Vol 37 (10) ◽  
pp. 766-771 ◽  
Author(s):  
M. C Costa ◽  
J Gaspar ◽  
K Mansinho ◽  
F Esteves ◽  
F Antunes ◽  
...  

2021 ◽  
Vol 7 (10) ◽  
pp. 856
Author(s):  
Carmen de la Horra ◽  
Vicente Friaza ◽  
Rubén Morilla ◽  
Juan Delgado ◽  
Francisco J. Medrano ◽  
...  

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.


2021 ◽  
Vol 7 (7) ◽  
pp. 546
Author(s):  
Estelle Menu ◽  
Jean-Sélim Driouich ◽  
Léa Luciani ◽  
Aurélie Morand ◽  
Stéphane Ranque ◽  
...  

Few data are available in the literature regarding Pneumocystis jirovecii infection in children under 3 years old. This retrospective cohort study aimed to describe medically relevant information among them. All children under 3 years old treated in the same medical units from April 2014 to August 2020 and in whom a P. jirovecii evaluation was undertaken were enrolled in the study. A positive case was defined as a child presenting at least one positive PCR for P. jirovecii in a respiratory sample. Medically relevant information such as demographical characteristics, clinical presentation, microbiological co-infections, and treatments were collected. The objectives were to describe the characteristics of these children with P. jirovecii colonization/infection to determine the key underlying diseases and risk factors, and to identify viral respiratory pathogens associated. The PCR was positive for P. jirovecii in 32 children. Cardiopulmonary pathologies (21.9%) were the most common underlying disease in them, followed by severe combined immunodeficiency (SCID) (18.8%), hyaline membrane disease (15.6%), asthma (9.4%) and acute leukaemia (6.3%). All SCID children were diagnosed with pneumocystis pneumonia. Co-infection with Pj/Rhinovirus (34.4%) was not significant. Overall mortality was 18.8%. Paediatric pneumocystis is not restricted to patients with HIV or SCID and should be considered in pneumonia in children under 3 years old.


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