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Experimental and Clinical... Aug 2012Pneumocystis jiroveci pneumonia is a rare but lethal complication in renal transplant recipients. Dose reduction of immunosuppressive agents in such situations is...
OBJECTIVES
Pneumocystis jiroveci pneumonia is a rare but lethal complication in renal transplant recipients. Dose reduction of immunosuppressive agents in such situations is recommended, but its quantity and safety are unclear.
MATERIALS AND METHODS
From January 2001 to January 2011, twenty of one thousand forty-six renal transplant recipients in a single center developed Pneumocystis jiroveci pneumonia, which was diagnosed by the Giemsa and Gomori methenamine silver stains from a specimen of bronchoalveolar lavage.
RESULTS
We found that timing of the first immunosuppressant reduction of the Pneumocystis jiroveci pneumonia survivor (mean, 1.4 days after admission) was significantly earlier than that of the deceased patient (mean, 5.1 days after admission). Logistic regression analysis indicated that for those whose immunosuppressants were reduced more aggressively (either 1 of the immunosuppressants was reduced by more than 50% within 2 days of hospitalization) were significantly more likely to survive (mortality risk, OR, 0.074 [95% CI, 0.01-0.84]; P = .035). In addition, none of the survivors developed acute rejection or allograft necrosis during a mean follow-up of 2 years.
CONCLUSIONS
Dosage reduction of immunosuppressive agents in renal transplant recipients with Pneumocystis jiroveci pneumonia should be prompt and sufficient. Aggressive immuno-suppressant dosage reduction is safe in such circumstance and is associated with minimal risk of in-hospital and long-term acute allograft rejection.
Topics: Acute Disease; Adult; Aged; Bronchoalveolar Lavage Fluid; Chi-Square Distribution; Drug Administration Schedule; Drug Therapy, Combination; Female; Graft Rejection; Hospital Mortality; Hospitalization; Humans; Immunosuppressive Agents; Kidney Transplantation; Logistic Models; Male; Middle Aged; Odds Ratio; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome
PubMed: 22765304
DOI: 10.6002/ect.2012.0015 -
Infection and Immunity Oct 2010Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV(+) subjects and has been associated with development of chronic obstructive...
Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV(+) subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural Pneumocystis jiroveci transmission were evaluated. SHIV-infected macaques were exposed to P. jiroveci by cohousing with immunosuppressed, P. jiroveci-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant Pneumocystis-kexin protein (KEX1) and evidence of Pneumocystis colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became Pneumocystis colonized (Pc(+)) by 8 weeks post-SHIV infection, while 4 animals remained Pneumocystis colonization negative (Pc(-)) throughout the study. In experiment 2, 11 of 17 animals became Pneumocystis colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc(-). Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc(-), compared to Pc(+) monkeys, in experiments 1 (P = 0.013) and 2 (P = 0.022). Pc(-) monkeys had greater percentages of Pneumocystis-specific memory B cells after SHIV infection compared to Pc(+) monkeys (P = 0.037). After SHIV infection, Pc(+) monkeys developed progressive obstructive pulmonary disease, whereas Pc(-) monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of Pneumocystis colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective Pneumocystis-specific memory B-cell response is maintained despite progressive loss of CD4(+) T cells during SHIV infection.
Topics: Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; HIV Infections; Humans; Immunity, Humoral; Macaca fascicularis; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Disease, Chronic Obstructive; Simian Acquired Immunodeficiency Syndrome
PubMed: 20660609
DOI: 10.1128/IAI.00507-10 -
Frontiers in Immunology 2021is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is... (Review)
Review
is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism's cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/ interactions.
Topics: Animals; Fungal Proteins; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammation Mediators; Lectins, C-Type; Ligands; Membrane Glycoproteins; Pneumocystis carinii; Pneumonia, Pneumocystis; Signal Transduction; beta-Glucans
PubMed: 34975910
DOI: 10.3389/fimmu.2021.798214 -
Revista Da Sociedade Brasileira de... 2023
Topics: Humans; Pneumonia, Pneumocystis; Risk Factors; Adrenal Cortex Hormones; Pneumocystis carinii
PubMed: 36820664
DOI: 10.1590/0037-8682-0553-2022 -
Medical Mycology Sep 2021We conducted a pilot study of patients with cystic fibrosis (CF) to assess intra-family transmission of P. jirovecii and compare it with data on other prevalent... (Comparative Study)
Comparative Study Observational Study
UNLABELLED
We conducted a pilot study of patients with cystic fibrosis (CF) to assess intra-family transmission of P. jirovecii and compare it with data on other prevalent pathogens such as P. aeruginosa and S. pneumoniae, in which respiratory transmission has already been documented. Oral swab samples from 10 patients with CF and 15 household members were collected at baseline and 2 weeks later. P. aeruginosa and S. pneumoniae were assessed using standardized culture methods and PCR, and P. jirovecii was assessed using real and nested PCR, genotyping the positive samples by direct sequencing. P. aeruginosa cultures were positive for 7/10 (70%) of patients with CF at baseline and was identified by PCR in 8/10 (80%) of cases at baseline and 2 weeks later. S. pneumoniae cultures were negative for all patients, but the microorganism was identified by PCR in two cases. P. jirovecii was detected by real time and nested PCR in 5/10 (50%) of the patients at the two time points. In the household members, P. aeruginosa and P. jirovecii were identified in 7/15 (46.7%), and S. pneumoniae was identified in 8/15 (53,3%). The concordance of positive or negative pairs of patients with CF and their household members was 33.3% (5/15) for P. aeruginosa, 46.7% (7/15) for S. pneumonia and 93.3% (14/15) for P. jirovecii. The concordance for P. jirovecii genotypes among five pairs with available genotype was 100%. This study suggests for the first time the possible transmission of Pneumocystis in the home of patients with CF, indicating that patients and their household members are reservoirs and possible sources of infection.
LAY SUMMARY
This study suggests for the first time the possible transmission of Pneumocystis in the family environment of patients with cystic fibrosis, indicating that patients and their household members are reservoirs and possible sources of this infection.
Topics: Adolescent; Adult; Child; Cystic Fibrosis; Family Characteristics; Female; Genotype; Humans; Infectious Disease Transmission, Vertical; Male; Pilot Projects; Pneumococcal Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Pseudomonas Infections; Pseudomonas aeruginosa; Streptococcus pneumoniae; Young Adult
PubMed: 33693837
DOI: 10.1093/mmy/myab010 -
Antimicrobial Agents and Chemotherapy Oct 2019
Topics: Caspofungin; Catalytic Domain; Echinocandins; Glucosyltransferases; Humans; Mutagenesis, Site-Directed; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 31548210
DOI: 10.1128/AAC.01296-19 -
The Cochrane Database of Systematic... Apr 2015Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air).
SEARCH METHODS
For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS.
SELECTION CRITERIA
Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality.
MAIN RESULTS
Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence).
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Adult; Chemotherapy, Adjuvant; Humans; Hypoxia; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 25835432
DOI: 10.1002/14651858.CD006150.pub2 -
The Pediatric Infectious Disease Journal Jan 2012This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of...
This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoietic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.
Topics: Anti-Infective Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Severe Combined Immunodeficiency; Survival Analysis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 21817949
DOI: 10.1097/INF.0b013e31822db772 -
Medical Science Monitor : International... Aug 2022BACKGROUND Sepsis is a serious threat to human life, particularly in immunocompromised patients; hence, early diagnosis and targeted treatment are important. Metagenomic...
BACKGROUND Sepsis is a serious threat to human life, particularly in immunocompromised patients; hence, early diagnosis and targeted treatment are important. Metagenomic next-generation sequencing (NGS) has significant advantages over traditional diagnostic methods. This study investigated the clinical value of NGS for pathogen identification in immunocompromised patients with sepsis. MATERIAL AND METHODS From July 2020 to September 2021, 90 consecutive patients with sepsis were enrolled in this prospective study. The patients were divided into 2 groups: an immunocompromised group (n=30) and an immunocompetent group (n=60). The pathogens causing sepsis were concurrently identified using NGS and traditional diagnostic methods. The pathogen detection rates and the spectrum of pathogens identified were compared according to the method of detection and between the immunocompromised and immunocompetent groups. RESULTS Of the 90 patients, 77 (86%) were positive for 1 or more pathogens using NGS, and 50 (56%) were positive using traditional detection methods. The positivity rate of sputum and bronchoalveolar lavage fluid was higher than that of blood samples. Pneumocystis jirovecii and cytomegalovirus infections were more common in the immunocompromised group than in the immunocompetent group. CONCLUSIONS The performance of NGS in identifying pathogens for patients with sepsis is better than that of traditional detection methods, especially in immunocompromised patients. Pneumocystis jirovecii and cytomegalovirus infections are more common in immunocompromised patients.
Topics: Bronchoalveolar Lavage Fluid; Cytomegalovirus Infections; High-Throughput Nucleotide Sequencing; Humans; Immunocompromised Host; Pneumocystis carinii; Prospective Studies; Sepsis
PubMed: 35957507
DOI: 10.12659/MSM.937041 -
Current Opinion in Microbiology Dec 2017Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the... (Review)
Review
Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the field in ascertaining the true impact of Pneumocystis in human infection. However the recent release of the genome as well as in advances in understanding host genetics, and other risk factors for infection and robust experimental models of disease have shed new light on the impact of this fungal pathogen as to better define populations at risk. This review will highlight these recent advances as well as highlight future needed areas of research.
Topics: Animals; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 29136537
DOI: 10.1016/j.mib.2017.10.019