<i>Pneumocystis jirovecii</i>Genotype Associated with Increased Death Rate of HIV-infected Patients with Pneumonia

Rabodonirina, Méja; Vaillant, L.; Taffé, Patrick; Nahimana, Aimable; Gillibert, René-Pierre; Vanhems, Philippe; Hauser, Philippe M.

doi:10.3201/eid1901.120140

Cited by 32 publications

(16 citation statements)

References 29 publications

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“…Of interest, a prospective single cohort study from San Francisco General Hospital consisting of 301 patients with laboratory-confirmed PCP over a period of Ͼ10 years demonstrated that although the receipt of recent sulfa prophylaxis was associated with mutant genotypes of P. jirovecii, the detection of mutant DHPS genotypes was not associated with mortality. This observation conflicts with findings from other authors (13,30).…”

Section: Discussioncontrasting

confidence: 56%

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

Chabé

George

et al. 2017

Antimicrob Agents Chemother

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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 treatmentlimiting 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-HIVinfected 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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Section: Discussioncontrasting

confidence: 56%

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

Chabé

George

et al. 2017

Antimicrob Agents Chemother

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“…The clinical significance of dhps mutations in relation to sulfa resistance remains unclear. Several studies showed associations of dhps mutations with poor outcomes for HIV-infected patients with PCP, including increased mortality (545) and treatment failure (58,546), but these associations were not supported in other studies (547,548).…”

Section: Strain Variation Of P Jiroveciimentioning

confidence: 91%

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

2018

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, a unique atypical fungus with an elusive lifestyle, has had an important medical history. It came to prominence as an opportunistic pathogen that not only can cause life-threatening pneumonia in patients with HIV infection and other immunodeficiencies but also can colonize the lungs of healthy individuals from a very early age. The genus includes a group of closely related but heterogeneous organisms that have a worldwide distribution, have been detected in multiple mammalian species, are highly host species specific, inhabit the lungs almost exclusively, and have never convincingly been cultured, making a fascinating but difficult-to-study organism. Improved molecular biologic methodologies have opened a new window into the biology and epidemiology of. Advances include an improved taxonomic classification, identification of an extremely reduced genome and concomitant inability to metabolize and grow independent of the host lungs, insights into its transmission mode, recognition of its widespread colonization in both immunocompetent and immunodeficient hosts, and utilization of strain variation to study drug resistance, epidemiology, and outbreaks of infection among transplant patients. This review summarizes these advances and also identifies some major questions and challenges that need to be addressed to better understand biology and its relevance to clinical care.

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“…Molecular typing methods, such as restriction fragment length polymorphism (RFLP) analysis, multiple locus sequence typing, direct DNA sequencing, and variable number of tandem repeats (VNTRs), have been used to analyze the epidemiology of P. jirovecii. A number of independent genomic regions, including the mitochondrial large subunit rRNA (mtLSU rRNA), the rRNA internal transcribed spacer (ITS), the intron of the nuclear 26S rRNA (26S), thymidylate synthase (TS), the variable region of the mitochondrial 26S rRNA gene (mt26S), dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), the region surrounding intron number 6 of the btubulin gene (b-tub), superoxide dismutase (SOD), cytochrome b (CYB), thioredoxin reductase (Trr1), 5-enolpyruvylshikimate-3-phosphate synthase (AROM), kexin-like serine protease (Kex1), and upstream conserved sequence (UCS) of the major surface glycoprotein (MSG) gene, have been used to analyze the genetic diversity of P. jirovecii (Esteves et al, 2009(Esteves et al, , 2010Gupta et al, 2013;Rabodonirina et al, 2013;Rostved et al, 2013;Wakefield, 1998). However, among these regions, the ITS, because of its high degree of genetic variation, might be the most discriminatory region for differentiating P. jirovecii isolates (Gupta et al, 2010;Le Gal et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Genotyping of Pneumocystis jirovecii isolates from human immunodeficiency virus-negative patients in China

Sun

Huang

Wang

et al. 2015

Infection, Genetics and Evolution

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Pneumocystis jiroveciiGenotype Associated with Increased Death Rate of HIV-infected Patients with Pneumonia

Abstract: Comorbidities might predict presence of specific fungal genotypes.

Cited by 32 publications

References 29 publications

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

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

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

Genotyping of Pneumocystis jirovecii isolates from human immunodeficiency virus-negative patients in China

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