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Background: Pneumocystis pneumonia is a well-recognized lung disease of premature and malnourished babies. Even though serologic studies have shown that children are exposed to Pneumocystis jirovecii early in life, the epidemiology of human P. jirovecii infection and the host-microorganism relationship in infancy remain poorly understood. The aim of the present study was to investigate the prevalence of P. jirovecii colonization in preterm infants and its possible association with medical complications., Methods: A prospective observational study of preterm infants (birth weight <1500 g and/or gestational age <32 weeks) was carried out. Identification of P. jirovecii colonization was performed by means of molecular techniques in nasal aspirated samples at birth., Results: A total of 128 preterm infants were included during the study period. Pneumocystis DNA was identified in 25.7% (95% confidence interval [CI], 17.8%-33.7%) of newborns studied. A significant increase of respiratory distress syndrome in colonized group, even after adjusting for confounding factors (odds ratio, 2.7 [95% CI, 1.0-7.5]; P = .04), was observed. No differences were observed in other medical conditions between the 2 groups., Conclusions: Pneumocystis jirovecii colonization is frequent in preterm births and could be a risk factor to develop respiratory distress syndrome among preterm infants., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Objective: To describe the epidemiological characteristics of the population with Pneumocystis jiroveci (P. jiroveci) pneumonia, analyzing risk factors associated with the disease, predisposing factors for admission to an intensive care unit (ICU), and prognostic factors of mortality., Design and Patients: A retrospective observational study was carried out, involving a cohort of patients consecutively admitted to a hospital in Spain from 1 January 2007 to 31 December 2011, with a final diagnosis of P. jiroveci pneumonia., Setting: The ICU and hospitalization service of Hospital del Mar, Barcelona (Spain)., Results: We included 36 patients with pneumonia due to P. jiroveci. Of these subjects, 16 required ICU admission (44.4%). The average age of the patients was 41.3 ± 12 years, and 23 were men (63.9%). A total of 86.1% had a history of human immunodeficiency virus (HIV) infection, and the remaining 13.9% presented immune-based disease subjected to immunosuppressive therapy. Risk factors associated to hospital mortality were age (51.8 vs. 37.3 years, P=.002), a higher APACHE score upon admission (17 vs. 13 points, P=.009), the need for invasive mechanical ventilation (27.8% vs. 11.1%, P=.000), requirement of vasoactive drugs (25.0% vs. 11.1%, P=.000), fungal coinfection (22.2% vs. 11.1%, P=.001), pneumothorax (16.7% vs. 83.3%, P=.000) and admission to the ICU (27.8% vs. 72.2% P=.000)., Conclusions: The high requirement of mechanical ventilation and vasoactive drugs associated with fungal coinfection and pneumothorax in patients admitted to the ICU remain as risk factors associated with mortality in patients with P. jiroveci pneumonia., (Copyright © 2013 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Pneumocystis jirovecii is a symbiotic respiratory fungus that causes pneumonia (PcP) in immunosuppressed patients. Because P. jirovecii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understanding of the organism persist. The release of a draft genome for the organism opens the door for the development of new genotyping approaches for studying its molecular epidemiology and global population structure. We identified and validated 8 putatively neutral microsatellite markers and 1 microsatellite marker linked to the dihydropteroate synthase gene (dhps), the enzymatic target of sulfa drugs used for PcP prevention and treatment. Using these tools, we analyzed P. jirovecii isolates from HIV-infected patients from three geographically distant populations: Uganda, the United States, and Spain. Among the 8 neutral markers, we observed high levels of allelic heterozygosity (average He, 0.586 to 0.842). Consistent with past reports, we observed limited global population structuring, with only the Ugandan isolates showing minor differentiation from the other two populations. In Ugandan isolates that harbored mutations in dhps, the microsatellite locus linked to dhps demonstrated a depressed He, consistent with positive directional selection for sulfa resistance mutations. Using a subset of these microsatellites, analyses of individual and paired samples from infections in San Francisco, CA, showed reliable typeability within a single infection and high discriminatory power between infections. These features suggest that this novel microsatellite typing approach will be an effective tool for molecular-epidemiological investigations into P. jirovecii population structure, transmission, and drug resistance.

Background: Opportunistic pulmonary infections (OPI) represent common life-threatening complications after solid organ transplantation. Our objective was to describe pulmonary infections caused by opportunistic pathogens in solid-organ transplant patients., Methods: We analyzed all adult solid organ recipients (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting all episodes of pulmonary opportunistic infection., Results: During the study period, 1656 solid organ transplants were performed and 188 opportunistic infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site of infection was the lung (21%) with 57.5% occurring between the first and sixth month posttransplantation. The most frequently isolated microorganism was Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs, 15%). Twenty-five patients with an opportunistic pulmonary infections died during the follow-up including, 16 related to the infection (40%). The causative organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%). Twenty-one patients with an opportunistic nonrespiratory infection died, five of them related to it (4%). Opportunistic pulmonary infection was associated with an increased mortality rate (P < .001). There was a trend toward a higher mortality among patients who developed OPI during the first 6 months after transplantation., Conclusions: Opportunistic pulmonary infections after solid organ transplantation are not infrequent. The period of risk for developing this infectious complications goes beyond the first 6 months posttransplantation. Mortality due to these infections was high in comparison to that of opportunistic nonrespiratory infections. It is important to keep a high index of suspicion for infectious complications during all posttransplant periods, as this is the first step toward a rapid diagnosis and adequate treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Genotypes of two different loci of the Pneumocystis jirovecii mitochondrial gene were studied in specimens from a total of 75 Pneumocystis pneumonia patients in Spain, France and Cuba. A new genotype of the mitochondrial small subunit rRNA gene of P. jirovecii (160A/196T) was identified, which was revealed to be the most common in these three countries, especially in Cuba where its proportion reached 93.8%. Our data imply that the new genotype might be circulating worldwide and also suggests that the distribution of P. jirovecii genotypes could be narrower in islands such as Cuba.

Background: Pneumocystis colonization in young HIV-infected patients has been poorly studied. The aim of this study was to analyze the prevalence of P jiroveci colonization in a cohort of young HIV-infected patients., Material and Methods: We designed a basal cross-sectional study in 20 young HIV-infected patients to determine the prevalence of P jiroveci colonization in oropharyngeal wash samples studied by nested polymerase chain reaction (PCR). Subsequently, patients were followed up during 50 weeks to observe the development of Pneumocystis pneumonia (PCP)., Results: P jiroveci colonization was detected in eight (40%) of the 20 oropharyngeal wash samples. Genotype 85C/248C was the most frequent. After 50 weeks of follow-up, one colonized patient with advanced immunodepression developed PCP., Conclusions: We have found a high prevalence of P jiroveci colonization in young HIV-infected patients with a major prevalence of genotype 1 (85C/248C). Further studies are necessary to clarify if Pneumocystis colonization could be a potential risk factor of developing PCP in young HIV infected patients., (Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

Pneumonia caused by the opportunistic organism Pneumocystis jirovecii is a clinically important infection affecting AIDS and other immunocompromised patients. The present study aimed to compare and characterise the frequency pattern of DNA sequences from the P. jirovecii mitochondrial large-subunit rRNA (mtLSU rRNA) gene, the dihydropteroate synthase (DHPS) gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA operon in specimens from Lisbon (Portugal) and Seville (Spain). Total DNA was extracted and used for specific molecular sequence analysis of the three loci. In both populations, mtLSU rRNA gene analysis revealed an overall prevalence of genotype 1. In the Portuguese population, genotype 2 was the second most common, followed by genotype 3. Inversely, in the Spanish population, genotype 3 was the second most common, followed by genotype 2. The DHPS wild-type sequence was the genotype observed most frequently in both populations, and the DHPS genotype frequency pattern was identical to distribution patterns revealed in other European studies. ITS types showed a significant diversity in both populations because of the high sequence variability in these genomic regions. The most prevalent ITS type in the Portuguese population was Eg, followed by Cg. In contrast to other European studies, Bi was the most common ITS type in the Spanish samples, followed by Eg. A statistically significant association between mtLSU rRNA genotype 1 and ITS type Eg was revealed.

Although asymptomatic carriers of Pneumocystis jirovecii with cystic fibrosis (CF) have been described previously, the molecular epidemiology of P. jirovecii in CF patients has not yet been clarified. This study identified the distribution and dynamic evolution of P. jirovecii genotypes based on the mitochondrial large-subunit (mt LSU) rRNA gene. The mt LSU rRNA genotypes of P. jirovecii isolates in 33 respiratory samples from CF patients were investigated using nested PCR and direct sequencing. Three different genotypes were detected: 36.3% genotype 1 (85C/248C); 15.1% genotype 2 (85A/248C); 42.4% genotype 3 (85T/248C); and 6% mixed genotypes. Patients studied during a 1-year follow-up period showed a continuous colonisation/clearance cycle involving P. jirovecii and an accumulative tendency to be colonised with genotype 3.

Pneumocystis jirovecii colonisation may occur among cystic fibrosis (CF) patients because of their underlying pulmonary disease. A wide epidemiological analysis was performed among CF patients from Spain to assess the prevalence of P. jirovecii colonisation and the distribution of different genotypes. P. jirovecii was identified by nested PCR targeting the mitochondrial large-subunit rRNA gene from sputum samples or oropharyngeal washes. The genotype was determined by direct sequencing. The prevalence of P. jirovecii colonisation among 88 consecutive CF patients was 21.5%. The polymorphisms identified were 85C/248C (45.4%), 85T/248C (27.2%) and 85A/248C (18.1%); in one case, a mix of genotypes was found. Colonisation was more frequent in subjects aged < 18 years (25.5% vs. 15.1%). Among the patients studied, 20.8% received treatment with azithromycin; all of these patients were colonised with P. jirovecii, but none developed Pneumocystis pneumonia (PcP) during a 1-year follow-up period. Concordance in the colonisation status of siblings suggested a common source of infection or person-to-person transmission.

This study describes the genotype distribution of Pneumocystis jiroveci in 79 respiratory samples obtained from 15 patients with acquired immunodeficiency syndrome (AIDS) with P. jiroveci pneumonia and 64 human immunodeficiency virus-negative subjects with different chronic pulmonary diseases. The genotyping was based in analysis of 2 independent genetic loci: the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) fragment (assessed by direct sequencing) and the gene for dihydropteroate synthase (DHPS; assessed by restriction fragment-length polymorphism). The mt LSU rRNA analysis revealed the presence of 3 different polymorphisms for both populations. The major genotype, 85C/248C, was found to be significantly higher in patients with AIDS and P. jiroveci pneumonia than in patients with pulmonary disease. The rate of genotypes 85A/248C and 85T/248C was similar in both groups. The analysis of DHPS genotypes assesses the prevalence of its 4 possible genotypes, with 35.5% of genotypes related to sulfa resistance. The data suggest a common source of infection between both groups.