Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey

Gal, Solène Le; Toubas, D.; Totet, Anne; Dalle, Frédéric; Bacar, Ahmed Abou; Meur, Yann Le; Nevez, Gilles; Accoceberry, Isabelle; Bailly, Éric; Bellanger, Anne Pauline; Bonhomme, Julie; Cateau, Estelle; Candolfi, Ermanno; Damiani, Céline; Dannaoui, Éric; Dardé, Marie‐Laure; Debourgogne, Anne; Delhaès, Laurence; Désoubeaux, Guillaume; Favennec, Loïc; Flori, Pierre; Gabriel, Frédéric; Iriart, Xavier; Lachaud, Laurence; Leterrier, Marion; Pape, Patrice Le; Machouard, Marie; Marty, Pierre; Maubon, Danièle; Millon, Laurence; Pomarès, Christelle; Pons, Denis; Rodier, Marie-Hélène

doi:10.1093/cid/ciz901

Cited by 27 publications

(20 citation statements)

References 11 publications

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“…In this study, we detected the nucleic acid sequences of the potential pathogenic fungus P. jirovecii in the blood of children in PICU. P. jirovecii is the pathogen of pneumocystis pneumonia, which can cause a severe lung disease called Pneumocystis jirovecii pneumonia ( Rabodonirina et al., 2013 ; Korkmaz Ekren et al., 2018 ; Le Gal et al., 2020 ). Interestingly, the abundance of P. jiroveci i in the blood of children with immunodeficiency disease was significantly higher than in those with non-immunodeficiency disease in PICU.…”

Section: Discussionmentioning

confidence: 99%

Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit

Yan

Liu

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

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Bloodstream infection is a life-threatening complication in critically ill patients. Multi-drug resistant bacteria or fungi may increase the risk of invasive infections in hospitalized children and are difficult to treat in intensive care units. The purpose of this study was to use metagenomic next-generation sequencing (mNGS) to understand the bloodstream microbiomes of children with suspected sepsis in a pediatric intensive care unit (PICU). mNGS were performed on microbial cell-free nucleic acid from 34 children admitted to PICU, and potentially pathogenic microbes were identified. The associations of serological inflammation indicators, lymphocyte subpopulations, and other clinical phenotypes were also examined. mNGS of blood samples from children in PICU revealed potential eukaryotic microbial pathogens. The abundance of Pneumocystis jirovecii was positively correlated with a decrease in total white blood cell count and immunodeficiency. Hospital-acquired pneumonia patients showed a significant increase in blood bacterial species richness compared with community-acquired pneumonia children. The abundance of bloodstream bacteria was positively correlated with serum procalcitonin level. Microbial genome sequences from potential pathogens were detected in the bloodstream of children with suspected sepsis in PICU, suggesting the presence of bloodstream infections in these children.

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Section: Discussionmentioning

confidence: 99%

Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit

Yan

Liu

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

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“…With the introduction of antiretroviral therapy and prophylaxis of PCP, the morbidity and mortality of PCP in HIV-infected patients has decreased significantly, but the incidence of PCP in non-HIV infected patients is increasing gradually, [1][2][3][4] especially in renal transplant recipients. 5 Following the first report of a cluster of 5 cases in Switzerland in 1991, at least 393 cases of PCP in renal transplant recipients have been reported in approximately 50 studies across the world (Table S1).…”

Section: Introductionmentioning

confidence: 99%

<p>Metagenomic Next-Generation Sequencing in Diagnosis of a Case of <em>Pneumocystis jirovecii</em> Pneumonia in a Kidney Transplant Recipient and Literature Review</p>

Chen¹,

He²,

Li³

et al. 2020

IDR

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Background: Despite the increasing incidences of Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients, diagnosis of PCP remains challenging due to its nonspecific clinical presentation and the inadequate performance of conventional diagnostic methods. There is a need for novel diagnostic methods. Case Presentation: A 27-year-old woman developed acute pneumonia 4 months after renal transplantation. Blood tests revealed a low CD4 count, a normal 1,3-beta-D-glucan level and other changes typical of inflammatory responses. Chest imaging showed bilateral diffuse infiltrates. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find Pneumocystis organisms. There was also no evidence for other pathogens known to cause pneumonia in various antibody and culture tests. Direct metagenomic next-generation sequencing (mNGS) analysis of a BALF specimen identified a large number of P. jirovecii reads, allowing to confirm the diagnosis of PCP. Following treatment with trimethoprim-sulfamethoxazole for two weeks, the patient was cured and discharged. Conclusion: This case report supports the value of mNGS in diagnosing PCP, highlights the inadequate sensitivity of conventional diagnostic methods for PCP, and calls for the need to add PCP prophylaxis to the current Diagnosis and Treatment Guideline of Invasive Fungal Infections in Solid Organ Transplant Recipients in China.

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“…Impdh gene analysis could provide an additional marker of P. jirovecii circulation among SOT recipients who are specifically at risk for PCP occurrence in a context of nosocomial acquisition of P. jirovecii and PCP outbreaks. MLST analysis including impdh gene may strengthen the concept of acquisition and transmission of specific P. jirovecii strains in SOT recipients, which has previously been discussed [ 6 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 80%

“…These mixed infections may be explained by an in-progress process of selection of P. jirovecii organisms under MPA pressure, wild P. jirovecii strains being not entirely replaced by a predominant mutant P. jirovecii strain. While MPA was initially considered to protect against P. jirovecii in the 1990s [ 8 ], an increase in PCP cases in SOT recipients has been reported, particularly in RTR, in a context of nosocomial infection over the past 15 years [ 6 , 27 ]. At present, MPA is identified as one of risk factors for PCP [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…PCP occurs in 5–15% of solid organ transplant (SOT) recipients in the absence of prophylaxis, with a mortality rate up to 49% [ 4 , 5 ]. The frequency of PCP seems to increase in SOT recipients, specifically in renal transplant recipients (RTR), particularly when the transplantation is not recent, when the patients are no longer subjected to PCP prophylaxis and when the acquisition of P. jirovecii is nosocomial [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid

Hoffmann

Nevez

Moal

et al. 2021

JoF

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Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.

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Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey

Cited by 27 publications

References 11 publications

Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit

Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit

<p>Metagenomic Next-Generation Sequencing in Diagnosis of a Case of <em>Pneumocystis jirovecii</em> Pneumonia in a Kidney Transplant Recipient and Literature Review</p>

Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid

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