Diagnosis Of Pneumocystis Jirovecii Pneumonia Research Articles

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

Rapid Diagnosis of Pneumocystis jirovecii Pneumonia and Respiratory Tract Colonization by Next-Generation Sequencing

ObjectivesTo describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.MethodsWe examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.ResultsAmong 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.ConclusionDetection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.

A case of hypercalcemia from Pneumocystis jirovecii in an immunosuppressed non-HIV patient

BackgroundThe prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile.Case PresentationA 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia.ConclusionsHerein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.

Clinical Performance of BALF Droplet Digital PCR for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonization

BackgroundAccurate differentiation between Pneumocystis jirovecii (Pj) infection and colonization is crucial for effective treatment. MethodsFrom September 2016 to June 2022, 89 immunocompromised patients with unexplained lung infiltrates and clinical suspicion of Pj pneumonia were enrolled at Peking University People's Hospital. Bronchoalveolar lavage fluid (BALF) of these patients were detected by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). ResultsThe performance of ddPCR was superior to qPCR in detecting Pj infection. Area under the curve was 0.97 (95%CI: 0.94–1) for ddPCR of the BALF in all patients. The optimal threshold value for discriminating Pj infection from colonization was 13.98 copies/test, with a sensitivity of 97.96%, specificity of 85.71%. No obvious correlation between ddPCR copy number and disease severity was observed. ConclusionBALF ddPCR exhibits robust potential in detecting Pj and effectively discriminating colonization and infection.

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).

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

SUMMARYPneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

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.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with Pneumocystis jirovecii pneumonia.

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. The median age of the 249 patients was 63 [IQR: 53-73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

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

BackgroundPneumocystis 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.MethodsThis 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 β-D-glucan levels was also evaluated for PCP diagnosis.ResultsA 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 β-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 β-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%).ConclusionsRadiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum β-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 registrationClinicalTrials.gov (NCT05701631).

A Case Report of Pulmonary Alveolar Proteinosis with Associated Opportunistic Infection of Pneumocystis jirovecii and Molluscum Contagiosum

Abstract Pulmonary alveolar proteinosis (PAP) is an idiopathic rare diffuse pulmonary disease, first described in 1958 by Rosen et al. Its estimated prevalence is about 1 in 3.7–6.9 × 106 with a male: female ratio of 1:1–2:1. Majority of the patient’s age ranges between 20 and 50 years. PAP on microscopy is characterized by the presence of massive insoluble, amorphous, phospholipid-rich protein deposits in the bronchial and alveolar cavities. Most patients with acquired PAP present with cough and exertional dyspnea. It has been studied that there is increased risk of superinfection in PAP with opportunistic organisms like pneumocystis and vice versa. Definitive diagnosis of Pneumocystis jirovecii pneumonia rests on the demonstration of the organism within the alveoli by special stains like Grocott Methenamine Silver stain. Molluscum contagiosum (MC) is a common superficial skin infection caused by the poxvirus. MC is characterized by painless papules commonly seen in children and immunocompromised individuals. Here, we present a 34-year-old female who had complaints of severe difficulty in breathing and was brought dead to our hospital. On external examination, she had multiple warts over chest, abdomen, and over genitalia. Internal examination was unremarkable. Specimens of kidney, lung, and skin biopsy of genital warts sent for histopathological examination revealed acute tubular necrosis, P. jirovecii with PAP, and MC respectively.

Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study

Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to The European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95%CI, 2.16-14.1; P< .001), IMIDs (OR, 2.19; 95%CI, 1.05-4.60; P= .037), long-term corticosteroid exposure (OR, 2.07; 95%CI, 1.03-4.31; P= .045), cysts in sputum/BAL smears (OR, 1.92; 95%CI, 1.02-3.62; P= .043), and SOFA score at admission (OR, 1.58; 95%CI, 1.39-1.82; P< .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95%CI, 1.03-2.71; P= .035), especially for a prednisone daily dose≥ 10mg (OR, 1.80; 95%CI, 1.14-2.85; P= .010). Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.

Diagnostic challenge of Pneumocystis jirovecii pneumonia infection mimicking interstitial lung disease in initially HIV negative patient

Background: Pneumocystis jirovecii pneumonia (PJP) infections are common in immunocompromised patients and are rarely found in immunocompetent patients. Lung radiology in PJP patients could mimic the appearance of interstitial lung disease (ILD) and could be used to diagnose HIV-negative patients. Clinicians should rule out false negatives in patients with patterns suggestive of opportunistic infections and risk factors for HIV infection. Case illustration: A 34-year-old man presented with a chief complaint of shortness of breath, had history of 15 years of smoking, and daily chlorine exposure. The radiology pattern and initial HIV-negative test results suggested an ILD diagnosis. Owing to persistent symptoms despite initial management and the presence of risk factors, repeat HIV testing was initiated and was positive. The patient was treated with cotrimoxazole and showed rapid clinical improvement. Discussion: The diagnosis of PJP in our patient was based on radiology and an HIV-positive status. In patients who are not immunocompromised, the diagnosis of PJP is unlikely, and other diagnoses, such as ILD, should be considered. However, in the HIV testing window period of infection, a poor advanced state of HIV could cause a false negative result. Therefore, clinical judgement is essential in suspecting such a result. The empirical treatment course of cotrimoxazole has been shown to provide better clinical outcomes in PJP. Conclusion: The possibility of PJP must be considered in patients with initially HIV-negative results, especially in patients with risk factors and clinical symptoms suggestive of immunocompromise. While some ILD showed similar PJP, the risk factors for ILD and PCP could be distinguishing factors. Retesting for HIV infection can confirm the diagnosis and rule out false-negative results.

1510. Evaluation of Quantitative (1,3)-β-D-glucan in Prediction of Pneumocystis jirovecii Pneumonia in Patients Living with HIV in New York

Abstract Background (1,3)-β-D-glucan (BDG) has been utilized as an indirect marker for Pneumocystis jirovecii pneumonia (PJP). The clinical utility of BDG, however, is limited because of uncertainty in interpreting quantitative values. A correlation was drawn between quantitative BDG and the diagnosis of PJP in hospitalized patients living with human immunodeficiency virus (HIV) at four affiliate campuses of the Montefiore Health System in the Bronx, NY. Methods All Pneumocystis direct fluorescent assays (DFA), polymerase chain reactions (PCR) either from bronchoalveolar lavage (BAL) fluid or sputum, and quantitative BDG assays either from serum or BAL fluid were retrieved from the Montefiore microbiology laboratory (date range: 8/1/18 - 8/31/22). Results from hospitalized patients with HIV whose CD4 count within 3 months were available, with either PJP DFA or PCR result within 7 days of serum BDG and lactate dehydrogenase (LDH) test were selected (n = 146). CD4 count was grouped into &amp;lt; 50 (n = 106), 50-100 (n = 15), 100-200 (n = 16), and &amp;gt;200 (n = 9). BDG, LDH, and CD4 were considered as input variables in a logistic regression model for true PJP status. The area under the curve (AUC) of the empirical receiver operating characteristic (ROC) curve with 95% confidence intervals (CI) was estimated based on trapezoidal area. Comparisons between ROC curve areas were performed via contrast matrix to take differences of the AUC of the empirical ROC curves and chi-square testing. Results Of the 146, 29 had PJP detected and 117 did not. When BDG only was considered, the AUC of the ROC curve was 0.78. When LDH quartiles (cutoffs: 232, 334, and 480 U/L) were considered with BDG, there was a statistically significant increase in AUC (0.84 vs. 0.78; p = 0.025). Adding CD4 group did not influence AUC. Figure 1 ROC curves for BDG only, BDG with CD4 count, BDG with LDH quartile, and BDG with CD4 group and LDH quartile combined Table 1 Area under the curve calculated for the ROC curves for BDG only, BDG with CD4 count, BDG with LDH quartile, and BDG with CD4 group and LDH quartile combined Conclusion The test characteristics (AUC) improved when LDH quartiles were used in conjunction with BDG, suggesting a better prediction of PJP diagnosis when BDG and LDH were considered together. This result supports further investigation of clinical markers of PJP given the limitations of establishing a microbiologic diagnosis. Further steps of the investigation will involve analyzing if other clinical factors including HIV viral load, oxygen saturation, and radiographical reading, influence predictability of PJP. Disclosures All Authors: No reported disclosures

830. Risk factors for late Pneumocystis jirovecii pneumonia in kidney transplant recipients: A Case-Control Study of United States Renal Data System Data

Abstract Background Organ transplant recipients are at increased risk of potentially life-threatening opportunistic infections, including Pneumocystis jirovecii pneumonia (PJP). Given the use of effective prophylaxis, PJP has become less common, especially during the first-year post-transplant. Recent data has shown that the risk of infection has shifted within the first 2 years after discontinuing prophylaxis. We aimed to determine risk factors for late posttransplant PJP using a national database. Methods Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2019. To evaluate risk factors for late PJP, we performed logistic regression analysis by comparing characteristics between infected patients and their matched uninfected controls. Results We identified 407 cases with PJP and matched to 1628 controls (1:4). 60 (14.7%) of the cases occurred within one year post transplant and 347 (85.3%) patients were diagnosed after one year of transplant. In the late period, the median time between transplant and PJP diagnosis was 68.7 (IQR 28 -134.2) months. Seventy cases (20.1%) occurred between 12 and 24 months. In multivariate analysis (table 1), risk factors for late infection included a higher Elixhauser Comorbidity Index (ECI), history of cytomegalovirus disease, older donor age, use of antilymphocyte agents, history of re-transplant and a longer time of hemodialysis prior to transplant. Of note, in the early period, we found that having a living donor was protective. Multivariate analysis of risk factors for late Pneumocystis jirovecii pneumonia Conclusion Our findings highlight the importance of a timely transplant to mitigate the risk of post-transplant PJP in the late post-transplant period where prophylaxis is not routinely used. These results also raise the consideration of PJP prophylaxis in the late period in patients diagnosed with CMV disease, history of re transplant and recent use of antilymphocyte agents. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support

Negative serum (1,3) -β-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR

ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Long-term Outcomes of Patients With HIV and Pneumocystis jirovecii Pneumonia in the Antiretroviral Therapy Era.

Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in people with HIV (PWH). However, there are limited data on long-term outcomes of PCP in the antiretroviral therapy (ART) era. We conducted a secondary analysis of 2 prospective studies on 307 PWH, 81 with prior PCP, with a median follow-up of 96 weeks. Laboratory data were measured at protocol-defined intervals. We reviewed clinically indicated chest computerized tomography imaging in 63 patients with prior PCP at a median of 58 weeks after PCP diagnosis and pulmonary function tests (PFTs) of patients with (n = 10) and without (n = 14) prior PCP at a median of 18 weeks after ART initiation. After 96 weeks of ART, PWH with prior PCP showed no significant differences in laboratory measurements, including CD4 count, when compared with those without prior PCP. Survival rates following ART initiation were similar. However, PWH with prior PCP had increased evidence of restrictive lung pathology and diffusion impairment in PFTs. Furthermore, on chest imaging, 13% of patients had bronchiectasis and 11% had subpleural cysts. Treatment with corticosteroids was associated with an increased incidence of cytomegalovirus disease (odds ratio, 2.62; P = .014). PCP remains an important opportunistic infection in the ART era. While it did not negatively affect CD4 reconstitution, it could pose an increased risk for incident cytomegalovirus disease with corticosteroid treatment and may cause residual pulmonary sequelae. These findings suggest that PCP and its treatment may contribute to long-term morbidity in PWH, even in the ART era.

Metagenomic next‐generation sequencing for pneumocystis jirovecii pneumonia in patients with connective tissue disease

AbstractBackgroundAccurate diagnosis of Pneumocystis jirovecii pneumonia (PJP) is challenging, and the delayed diagnosis of PJP is associated with high mortality in patients with connective tissue disease (CTD). Metagenomic next‐generation sequencing (mNGS) technology facilitates etiological diagnosis of various infectious diseases, with promising application in diagnosing PJP. This study aimed to investigate the value of mNGS using bronchoalveolar lavage fluid (BALF) for diagnosing PJP infection.MethodsData from 55 patients with CTD and suspected pulmonary infection was retrospectively collected and analysed. A PJP group and non‐PJP group were formed. The clinical manifestations, laboratory test results, treatment methods, and outcomes were summarized. BALF mNGS results were compared with traditional pathogen tests (TPT) and serum 1,3‐beta‐D‐glucan (BDG) testing.ResultsThe mean age of PJP patients was 54 years, and 59% (10/17) of the patients were female. A significant difference was found between the average daily dose of prednisone administered to the PJP group and non‐PJP group (25 mg vs. 16 mg, P &lt; 0.001). The PJP group had a significantly higher incidence of dyspnoea (88% [15/17] vs. 16% [6/38], P &lt; 0.001) and elevated serum BDG level (167.73 vs. 30.67 pg/mL, P &lt; 0.001). BALF mNGS was more sensitive than both TPT (100% [95% confidence interval {CI}: 77.1%–100%] vs. 11.8% [95% CI: 2.1%–37.7%], P &lt; 0.001) and serum BDG (100% [95% CI: 77.1%–100%] vs. 85.7% [95% CI: 42%–99.2%], P &lt; 0.001). BALF mNGS was more specific than serum BDG (89.5% [95% CI: 74.3%–96.6%] vs. 46.7% [95% CI: 22.3%–72.6%], P = 0.493). Co‐infection with cytomegalovirus (CMV) was more common in the PJP patients than in the non‐PJP patients (59% [10/17] vs. 11% [4/38], respectively, P &lt; 0.001).ConclusionBALF mNGS technology is highly effective for diagnosing PJP in patients with CTD and identifying co‐infections.

A Case of Pneumocystis jirovecii Pneumonia in an Infant with Ataxia-Pancytopenia Syndrome

BackgroundAtaxia-pancytopenia syndrome (ATXPC), a rare autosomal dominant disorder caused by pathogenic variants in the SAMD9L gene, is characterized by variable onset and severity of cerebellar ataxia, hematologic cytopenias, and immunodeficiency of myeloid, B-, and NK-cells. ATXPC has been associated with viral and bacterial infections, but no cases of opportunistic PJP have been reported. CaseAt 6 weeks of age, the patient was admitted to the hospital for acute hypoxemic respiratory failure due to rhino/enterovirus bronchiolitis, requiring supplemental oxygen. The increased oxygen requirement later led to intubation. A chest x-ray showed diffuse bilateral opacities concerning for pediatric acute respiratory distress syndrome (PARDS). Bronchoalveolar lavage and silver stain revealed organisms morphologically suggestive of Pneumocystis jirovecii pneumonia (PJP), which was confirmed with a positive serum beta-glucan. Based on the diagnosis of PJP, the patient was started on steroids and Bactrim. Immunology was consulted for further evaluation for possible underlying immunodeficiency. The patient had a normal newborn screening. HIV PCR was negative. Repeated TRECs, CD3+, CD8+, CD19+, and immunoglobulin levels (IgG, IgE) were within normal limits, but modest reduction of CD45 RA/RO ratio and IgA were observed. Additionally, natural killer cell function was low. T-cell proliferation to mitogens were normal, but significantly decreased to candida and tetanus antigens. A significant reduction in the expression of HLA-ABC and HLA-DR was observed in the lymphocytes and monocytes of the patient compared to the control. Interestingly, HLA-DR expression on monocytes was particularly affected. A next-generation sequencing of primary immunodeficiency genes identified likely pathogenic, maternally inherited variants: a heterozygous SAMD9L variant (ataxia-pancytopenia syndrome) and NLRP12 variant (familial cold autoinflammatory syndrome 2). DiscussionATXPC has been associated with variable cellular immunodeficiencies. While prior studies have reported recurrent bacterial and viral infections in ATXPC patients, this case is the first to document a PJP opportunistic infection in an infant. It is possible that the NLRP12 variant found in this patient could have also contributed to this clinical presentation. Early diagnosis of ATXPC through clinical recognition and genetic testing may improve prognosis.

Pneumocystis jirovecii Pneumonia Diagnostic Approach: Real-Life Experience in a Tertiary Centre.

Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients entails high mortality and requires adequate laboratory diagnosis. We compared the performance of a real time-PCR assay against the immunofluorescence assay (IFA) in the routine of a large microbiology laboratory. Different respiratory samples from HIV and non-HIV-infected patients were included. The retrospective analysis used data from September 2015 to April 2018, which included all samples for which a P. jirovecii test was requested. A total of 299 respiratory samples were tested (bronchoalveolar lavage fluid (n = 181), tracheal aspirate (n = 53) and sputum (n = 65)). Forty-eight (16.1%) patients fulfilled the criteria for PJP. Five positive samples (10%) had only colonization. The PCR test was found to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96%, 98%, 90% and 99%, compared to 27%, 100%, 100% and 87%, for the IFA, respectively. PJ-PCR sensitivity and specificity were >80% and >90% for all tested respiratory samples. Median cycle threshold values in definite PJP cases were 30 versus 37 in colonized cases (p < 0.05). Thus, the PCR assay is a robust and reliable test for the diagnosis PJP in all respiratory sample types. Ct values of ≥36 could help to exclude PJP diagnosis.