Pneumocystosis: Survey and DHPS Genotype Analysis in 14 Parisian Hospitals in 2003 and 2004

Magne, Denis; Lacube, Philippe; Angoulvant, Adéla; Meliani, Leila; Botterel, Françoise; Bougnoux, Marie‐Elisabeth; Chochillon, Christian; Cornet, Muriel; Dannaoui, Éric; Datry, A.; Dunand, J.; Galeazzi, G.; Bouges-Michel, C.; Yera, Hélène; Sarfati, Claudine; Roux, Patricia

doi:10.1111/j.1550-7408.2006.00191.x

Cited by 5 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical impact of these mutations is still controversial. In Europe, the prevalence of the double mutated genotype remains low (<3%), whereas prevalence as high as 40% has been reported in the USA [36–38]. Some studies did not find any link between DHPS mutations and treatment setting or clinical outcome [5,39], whereas a threefold increase in mortality rate has been demonstrated for patients infected with Pneumocystis harbouring a DHPS mutation, compared with those infected with wild type‐DHPS Pneumocystis [16].…”

Section: Discussionmentioning

confidence: 99%

Linking Pneumocystis jiroveci sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae

Moukhlis

Boyer

Lacube

et al. 2010

Clinical Microbiology and Infection

View full text Add to dashboard Cite

Curative and prophylactic therapy for Pneumocystis jiroveci pneumonia relies mainly on cotrimoxazole, an association of trimethoprim and sulfamethoxazole (SMX). SMX inhibits the folic acid pathway through competition with para-aminobenzoic acid (pABA), one of the two substrates of the dihydropteroate synthase (DHPS), a key enzyme in de novo folic acid synthesis. The most frequent non-synonymous single nucleotide polymorphisms (SNPs) in P. jiroveci DHPS are seen at positions 165 and 171, the combination leading to four possible different genetic alleles. A number of reports correlate prophylaxis failure and mutation in the P. jiroveci DHPS but, because of the impossibility of reliably cultivating P. jiroveci, the link between DHPS mutation(s) and SMX susceptibility is not definitively proven. To circumvent this limitation, the yeast Saccharomyces cerevisiae was used as a model. The introduction of the P. jiroveci DHPS gene, with or without point mutations, directly amplified from a clinical specimen and cloned in a centromeric plasmid into a DHPS-deleted yeast strain, allowed a fully effective complementation. However, in the presence of SMX at concentrations >250 mg/L, yeasts complemented with the double mutated allele showed a lower susceptibility compared with strains complemented with either a single mutated allele or wild-type alleles. These results confirm the need for prospective study of pneumocystosis, including systematic determination of the DHPS genotype, to clarify further the impact of mutations on clinical outcome. Additionally, the S. cerevisiae model proves to be useful for the study of still uninvestigated biological properties of P. jiroveci.

show abstract

Section: Discussionmentioning

confidence: 99%

Linking Pneumocystis jiroveci sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae

Moukhlis

Boyer

Lacube

et al. 2010

Clinical Microbiology and Infection

View full text Add to dashboard Cite

show abstract

“…Despite a decrease in incidence associated with the introduction of the high antiretroviral therapies (HAART), pneumocystosis due to Pneumocystis jirovecii (or PcP for Pneumocystis pneumonia) remains one of the main fungal infection diagnosed in Europe in AIDS and other immunocompromised patients [1,2]. Due to strict host-species specificity, humans may be the main source of Pneumocystis jirovecii organisms and human-to-human and nosocomial transmission may occur [3].…”

Section: Introductionmentioning

confidence: 99%

Pneumocystosis: a network survey in the Paris area 2003–2008

Magne

Angoulvant

Botterel

et al. 2011

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

The aims of this network group were to collect epidemiological data of PcP cases in 14 hospitals in the Paris area and to determine the Di-Hydro Pteroate Synthase (DHPS) genotypes, genetic markers for possible sulfamide resistance. From January 1, 2003 to December 31, 2008, 993 (mean 166/year) PcP cases have been reported. Sixty-five percent of patients were HIV-positive. The median count of CD4 lymphocytes was 32/mm(3) (30 in HIV-positive patients, 152 in HIV-negative patients). In HIV-positive patients, PcP revealed the HIV infection in 39%. Among 304 PcP occurring in HIV known infected patients, no prophylaxis was prescribed for 64%; cotrimoxazole prophylaxis had been prescribed to 47 patients but only one of them had the right compliance. In HIV-negative patients (264), corticosteroids were prescribed in 59% and cytotoxic chemotherapies in 34%; 78% did not receive prophylaxis. One hundred sixty nine tumoral pathologies and 116 transplantations were notified. The mortality rate was 16% at day 14 (13% in HIV-positive patients, 26% in HIV-negative patients). Mutations in DHPS genes were detected in 18.5% of samples; 12.5% of patients were infected with several strains. The total annual number of cases has been stable for five years but the proportion of HIV-negative patients increased from 25% to 43%.

show abstract

Facteurs favorisants de la pneumocystose (PPC) chez les malades immunodéprimés non infectés par le VIH

Roblot

Godet

Kauffmann

et al. 2009

Journal de Mycologie Médicale

View full text Add to dashboard Cite

Pneumocystosis: Survey and DHPS Genotype Analysis in 14 Parisian Hospitals in 2003 and 2004

Cited by 5 publications

References 8 publications

Linking Pneumocystis jiroveci sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae

Linking Pneumocystis jiroveci sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae

Pneumocystosis: a network survey in the Paris area 2003–2008

Facteurs favorisants de la pneumocystose (PPC) chez les malades immunodéprimés non infectés par le VIH

Contact Info

Product

Resources

About