Study on mNGS Technique in Diagnosing Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients.

Objective: To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients. Methods: In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of Pneumocystis jirovecii (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-ß-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis. Results: Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, P = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly Pneumocystis jirovecii, human gammaherpesvirus 4 and Acinetobacter baumannii. Conclusion: mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.

Chest X-ray Features of HIV-Associated Pneumocystis Pneumonia (PCP) in Adults: A Systematic Review and Meta-analysis.

Background: The performance of chest x-ray (CXR) features for Pneumocystis pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to describe CXR changes in adults with HIV-associated laboratory-confirmed PCP, comparing these with non-PCP respiratory disease. Methods: We searched databases for studies reporting CXR changes in people >15 years old with HIV and laboratory-confirmed PCP and those with non-PCP respiratory disease. CXR features were grouped using consensus terms. Proportions were pooled and odds ratios (ORs) generated using random-effects meta-analysis, with subgroup analyses by CD4 count, study period, radiology review method, and study region. Results: Fifty-one studies (with 1821 PCP and 1052 non-PCP cases) were included. Interstitial infiltrate (59%; 95% CI, 52%-66%; 36 studies, n = 1380; I2 = 85%) and ground-glass opacification (48%; 95% CI, 15%-83%; 4 studies, n = 57; I2 = 86%) were common in PCP. Cystic lesions, central lymphadenopathy, and pneumothorax were infrequent. Pleural effusion was rare in PCP (0%; 95% CI, 0%-2%). Interstitial infiltrate (OR, 2.3; 95% CI, 1.4-3.9; I2 = 60%), interstitial-alveolar infiltrate (OR, 10.2; 95% CI, 3.2-32.4; I2 = 0%), and diffuse CXR changes (OR, 7.3; 95% CI, 2.7-20.2; I2 = 87%) were associated with PCP diagnosis. There was loss of association with alveolar infiltrate in African studies. Conclusions: Diffuse CXR changes and interstitial-alveolar infiltrates indicate a higher likelihood of PCP. Pleural effusion, lymphadenopathy, and focal alveolar infiltrates suggest alternative causes. These findings could be incorporated into clinical algorithms to improve diagnosis of HIV-associated PCP.

Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis.

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

Pneumocystis Pneumonia in a Patient With Alcoholic Hepatitis.

Pneumocystis jirovecii is an opportunistic fungus typically causing pulmonary infection in immunocompromised persons. We present a case of Pneumocystis jirovecii pneumonia (PJP) in a patient with alcoholic hepatitis and underlying cirrhosis. PJP in patients with alcoholic hepatitis or cirrhosis is sparsely reported in literature. This condition carries a poor prognosis and high mortality. Clinicians need to recognize alcohol use resulting in liver damage as a significant etiological risk factor for PJP.

[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia.

BACKGROUND: Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. METHODS: In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. RESULTS: BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. CONCLUSIONS: This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Pneumocystis jirovecii pneumonia in paediatric acute lymphoblastic leukaemia: A report from the multi-international clinical trial AIEOP-BFM ALL 2009.

Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear.

Comparing Polymerase Chain Reaction Testing of Nasopharyngeal Swab and Lower Respiratory Tract Specimens for the Diagnosis of Pneumocystis jirovecii Pneumonia.

Using nasopharyngeal (NP) swab samples instead of lower respiratory tract specimens for polymerase chain reaction (PCR) to diagnose Pneumocystis jirovecii pneumonia (PJP) may be better tolerated and improve diagnostic accessibility. In this 2-year Australian retrospective cohort study of patients with clinically suspected PJP, P jirovecii PCR on NP swab samples had perfect specificity but low sensitivity (0.66).

Comparison of the outcomes of Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients treated with and without biologics.

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

PURPOSE: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. METHODS: This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. RESULTS: Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION: These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

Pneumocystis jirovecii Pneumonia in a Patient With Localized Mycosis Fungoides Not Receiving Immunosuppressive Treatment.

Pneumocystis jirovecii pneumonia (PCP) is the most common opportunistic infection in patients with human immunodeficiency virus (HIV), but it may develop in patients without HIV, whose immune system is suppressed by anticancer or immunosuppressive agents even when indicating normal counts of CD4+ T cells. Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma, which is believed not to cause immunosuppressive conditions unless it develops leukosis or metastasis or is treated with anticancer drugs or systemic immunosuppressants. Here, we report a case of PCP in a patient with localized MF not receiving immunosuppressive treatment. The patient, a woman in her 70s, presented with persistent dyspnea. High-resolution computed tomography (HRCT) showed diffuse ground-glass opacities in both lungs. Bronchoalveolar lavage fluid was positive for P. jirovecii. Moreover, the cytomegalovirus antigenemia test was positive, whereas tests for anti-HIV and antihuman T-cell lymphotropic virus antibodies were negative. The patient was treated with trimethoprim-sulfamethoxazole, prednisolone, and ganciclovir, which gradually improved the symptoms and diminished diffuse ground-glass opacities on HRCT. This case exemplifies a rare presentation of PCP with mild MF that was not treated with chemotherapy or immunosuppressants. The possible mechanisms for the development of PCP are discussed.

Association between oral corticosteroid starting dose and the incidence of pneumonia in Japanese patients with ulcerative colitis: a nation-wide claims database study.

Background/Aims: A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30-40 mg). This may relate to physician's concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses. Methods: This retrospective cohort study used the Japan Medical Data Center claims database (2012-2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose < 30 mg), guideline-recommended (30-40 mg), and higher groups ( > 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort. Results: After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization. Conclusions: The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.

Molecular Study of Pneumocystis jirovecii in Respiratory Samples of HIV Patients in Chile.

Pneumocystis is an opportunistic fungus that causes potentially fatal pneumonia (PCP) in immunocompromised patients. The objective of this study was to determine the prevalence of P. jirovecii in HIV patients through phenotypic and molecular study, to investigate the genetic polymorphisms of P. jirovecii at the mitochondrial gene mtLSU and at the nuclear dihydropteroate synthase gene (DHPS), and by analysis of molecular docking to study the effect of DHPS mutations on the enzymatic affinity for sulfamethoxazole. A PCP prevalence of 28.3% was detected, with mtLSU rRNA genotypes 3 (33.3%) and 2 (26.6%) being the most common. A prevalence of 6.7% (1/15) mutations in the DHPS gene was detected, specifically at codon 55 of the amino acid sequence of dihydropteroate synthase. Molecular docking analysis showed that the combination of mutations at 55 and 98 codons is required to significantly reduce the affinity of the enzyme for sulfamethoxazole. We observed a low rate of mutations in the DHPS gene, and molecular docking analysis showed that at least two mutations in the DHPS gene are required to significantly reduce the affinity of dihydropteroate synthase for sulfamethoxazole.

A Case of Pneumocystis Pneumonia Developed During Rheumatoid Arthritis Treatment With Methotrexate and Golimumab.

Here, we report a case of an 87-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate (MTX) and golimumab who developed severe pneumocystis pneumonia (PCP), also known as Pneumocystis jirovecii pneumonia. The patient presented with chief complaints of dyspnea on exertion, dry cough, and fatigue. A high-resolution chest CT scan revealed diffuse, unevenly distributed ground-glass opacities throughout both lungs. The patient was clinically diagnosed with PCP based on the clinical settings, imaging, and a high level of serum ß-D-glucan. While the patient required high-flow oxygen therapy, low-dose trimethoprim/sulfamethoxazole and corticosteroid therapy improved her condition, and the patient was discharged on day 25. Although to our knowledge no case report has been published regarding PCP in patients with RA treated with golimumab, this case emphasizes the importance of attention to opportunistic infections in elderly patients receiving immunosuppressive therapy. MTX use alongside tumor necrosis factor inhibitors like golimumab may increase the risk of serious infections such as PCP. The case underscores the necessity of prophylactic measures and early intervention for PCP, highlighting the delicate balance between immunosuppression benefits and infection risks in RA management.

Pneumocystis jirovecii pneumonia presenting with severe, refractory hypercalcaemia in an immunosuppressed renal transplant patient: Review of the literature and novel biochemical insights.

Pneumocystis jirovecii pneumonia (PJP) is a rare but serious complication of immunosuppression post-solid organ transplantation. We present a case of refractory, severe hypercalcaemia due to PJP in a renal transplant recipient. Treatment of PJP led to normalisation of the patient's calcium levels, and clinical improvement. To further explore the proposed calcitriol-driven mechanism leading to hypercalcaemia in PJP, we performed biochemical analysis on pre- and post-treatment serum and bronchoalveolar lavage sample at the time of PJP diagnosis. We confirmed high circulating and pulmonary levels of calcitriol in acute, untreated PJP with severe hypercalcaemia. PJP treatment led to reduction of circulating calcitriol to within normal range. We present this case, together with a literature review of similar reported cases, and the novel biochemical evidence supporting extra-renal production of calcitriol by activated pulmonary macrophages as the mechanism underpinning hypercalcaemia in PJP.

Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).

Pneumocystis jirovecii pneumonia in a healthy immunocompetent patient: A case report and literature review.

Pneumocystis jirovecii pneumonia, typically an opportunistic infection, is commonly associated with risk factors such as low CD4+ lymphocyte count, underlying malignancies, organ transplantation, or immunosuppressive medications. However, occurrences in healthy individuals without known risk factors are exceptionally rare and sparsely documented. In our retrospective analysis of a 42-year-old male without past medical history at Abderrahmane Mami Hospital, Tunisia, Pneumocystis jirovecii pneumonia was diagnosed. The patient presented with fever, productive cough, hemoptysis, and a decline in general health. Clinical examination revealed fever and hypoxemia, and imaging studies demonstrated bilateral necrotic alveolar opacities. Despite empirical antibiotics, nonresponse necessitated bronchoscopy, confirming Pneumocystis jirovecii. Treatment with oral Sulfamethoxazole-Trimethoprim yielded excellent outcomes. This case highlights the potential occurrence of Pneumocystis jirovecii pneumonia in immunocompetent individuals, underscoring the importance of direct microbiological methods in assessing suggestive clinical and radiological features.

Case Report of COVID-19 and Pneumocystis coinfection in a pediatric patient with a history of receiving high dose steroid therapy.

We report the first case of a critically ill pediatric patient coinfected with coronavirus disease 2019 (COVID-19) and Pneumocystis jirovecii pneumonia (PCP). Instances of coinfection of COVID-19 and PCP are being increasingly reported as the COVID-19 pandemic continues. Because the combination can be life-threatening, timely diagnosis and treatment for PCP is necessary in cases where an immunocompromised patient contracts COVID-19.

Determining Pneumocystis jirovecii Colonisation from Infection Using PCR-Based Diagnostics in HIV-Negative Individuals.

BACKGROUND: Pneumocystis jirovecii pneumonia is increasingly diagnosed with highly sensitive PCR diagnostics in immunocompromised, HIV-negative individuals. We assessed the performance of our in-house quantitative PCR with the aim to optimise interpretation. METHODS: Retrospective audit of all positive P. jirovecii qPCRs on induced sputum or BAL fluid at a single centre from 2012 to 2023. Medical and laboratory records were analysed and people with HIV were excluded. Cases were categorised as colonisation, high-probability PCP or uncertain PCP infection against a clinical gold standard incorporating clinico-radiological data. Quantitative PCR assay targeting the 5s gene was utilised throughout the time period. RESULTS: Of the 82 positive qPCRs, 28 were categorised as high-probability PCP infection, 30 as uncertain PCP and 24 as colonisation. There was a significant difference in qPCR values stratified by clinical category but not respiratory sample type. Current assay performance with a cutoff of 2.5 × 105 copies/mL had a sensitivity of 50% (95% CI, 30.65-69.35%) and specificity of 83.33% (95% CI, 62.62-95.26%). Youden Index calculated at 6.5 × 104 copies/mL had a sensitivity of 75% (56.64-87.32%, 95% CI) and specificity of 66.67% (46.71-82.03%, 95% CI). High and low cutoffs were explored. Significant variables associated with infection were age > 70 years old, the presence of fever, hypoxia or ground glass changes. CONCLUSIONS: A single qPCR cutoff cannot reliably determine P. jirovecii infection from colonisation. Low and high cutoffs are useful, however, a large "possible infection" cohort will remain where interpretation of clinic-radiological factors remains essential. Standardisation of assays with prospective validation in specific immunocompromised groups will allow greater generalisability and allow large-scale prospective assay validation to be performed.

Epidemiology, Risk Factors, and Prophylaxis Use for Pneumocystis jirovecii Pneumonia in the Non-HIV Population: A Retrospective Study in Québec, Canada.

Background: Pneumocystis jirovecii pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and guidelines on appropriate prophylaxis are lacking. Methods: In this multicenter retrospective trial, all non-HIV adult cases admitted to hospitals in Québec City, Canada, between January 2011 and January 2021 with a diagnosis of PJP were assessed for eligibility. Results: An overall 129 cases of PJP were included. More than two-thirds had an underlying hematologic disease or an autoimmune/inflammatory condition. Prior to diagnosis, 83.7% were taking corticosteroids, 71.3% immunosuppressive agents (alone or in combination with corticosteroids), and 62% both. A diagnosis of PJP was noted in 22 patients receiving corticosteroids for treatment <28 days. Two patients developed PJP while undergoing corticosteroid monotherapy at a mean daily prednisone-equivalent dose <20 mg/d; 4.7% of our cohort received a PJP prophylaxis. Current recommendations or accepted clinical practices for PJP prophylaxis would not have applied to 48.8% of our patients. Conclusions: The use of corticosteroids-in monotherapy or in coadministration with other immunosuppressive agents-remains the principal risk factor for PJP in the non-HIV population. Current prophylaxis guidelines and accepted practices are insufficient to adequately prevent PJP and need to be broadened and updated.