Diagnosis Of Pneumocystis Carinii Pneumonia Research Articles

Pneumocystis pneumonia in HIV-positive and non-HIV patients: a retrospective comparative study from a lower-middle income country.

In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in pneumocystis pneumonia (PCP) infection among the human immunodeficiency virus (HIV)-positive and non-HIV patient populations. This retrospective analysis was conducted at the Aga Khan University Hospital, Karachi, via the collection and analysis of patient records with a diagnosis of "pneumocystosis" between January 2015 and October 2020. Additionally, the laboratory database was evaluated, and patients with a laboratory-confirmed diagnosis of PCP were included. During the study period, 52 laboratory-confirmed hospitalized PCP patients were identified. Of these, 23 and 29 patients were diagnosed using microscopy and polymerase chain reaction, respectively. 34.6% of our patients were HIV positive, with a median CD4 count of 20.5 cells/mm3 (range: 10.7-50.5). Other conditions identified were corticosteroid use, autoimmune diseases, malignancy, radiation, and chemotherapy. On chest imaging, consolidation was found in 30%, ground-glass opacities in 24%, and nodular infiltrates in 20% of the cases. HIV-positive patients had a lower hemoglobin level and a higher level of β-D-glucan at the time of admission, whereas non-HIV patients were found to have more co-morbid conditions than HIV patients. We observed no difference in clinical outcomes between the two populations. Factors associated with a poor prognosis among our patients included concomitant infections at the time of diagnosis, the need for invasive mechanical ventilation, and a longer duration of stay in the hospital as well as the intensive care unit.

An umbrella review of the diagnostic value of next-generation sequencing in infectious diseases.

An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs. We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs. Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections. This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.

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

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. 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. 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. 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.

Pneumocystose

AbstractThe Pneumocystis genus includes some species belonging to Ascomycota phylum. These micromycetes are atypical because they are presently uncultivable, resistant to amphotericin B and azoles but sensitive to sulfonamides and echinocandins. They have a strong pulmonary tropism and are airborne transmitted between host mammals of the same species. Pneumocystis jirovecii (P. jirovecii) is the species infecting humans. It is responsible for severe pneumonia in patients infected with human immunodeficiency virus (HIV). Pneumocystis pneumonia (PCP) remains the most common AIDS defining opportunistic infection in metropolitan France. However, PCP is currently more commonly observed in immunocompromised patients not infected with HIV The symptoms of PCP include the triad, fever, dyspnea and dry cough associated with ground-glass pictures at the chest CT-scan in relation to bilateral alveolar-interstitial pneumonia.The biological diagnosis of PCP is based on the detection of P. jirovecii by microscopy and PCR in lung samples, with broncho-alveolar lavage fluid remaining the reference sample. β-1,3-D-glucan detection in serum is an additional useful diagnostic tool. The sulfamethoxazole-trimethoprim combination is the first-line treatment while pentamidine, atovaquone, dapsone, and echinocandins represent second-line treatments.

CMV Infection and Lymphopenia: Warning Markers of Pneumocystis Pneumonia in Kidney Transplant Recipients.

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.

High prevalence of pneumocystis pneumonia in interstitial lung disease: a retrospective study.

Interstitial lung disease (ILD) is a new risk category for pneumocystis pneumonia (PCP) with a high mortality rate. The definite diagnostic criteria of PCP in ILD patients have not been established until now. The aims of this study were to identify potential risk factors of PCP in patients with ILD, and to evaluate the performance of metagenomic next-generation sequencing (mNGS), CD4 + T cell count, (1-3)-β-D-Glucan (BG) and lactate dehydrogenase (LDH) in the diagnosis of PCP in ILD patients. This is a retrospective, single-center, case-control study. ILD patients who underwent mNGS from December 2018 to December 2022 were included in the study. Based on the diagnosis criteria of PCP, these patients were divided into PCP-ILD and non-PCP-ILD groups. The potential risk factors for PCP occurrence in ILD patients were analysed via logistic regression. The diagnostic efficacy of mNGS was compared with serological biomarkers. 92 patients with ILD were enrolled, 31 of which had a definite PCP and were assigned to the PCP-ILD group while 61 were to the non-PCP-ILD group. The infection rate of PJ in ILD patients was 33.7% (31/92). The history of glucocorticoid therapy, CD4 + T cell count, BG level and traction bronchiectasis on HRCT were associated with PCP occurrence in ILD patients. LDH level did not reach statistical significance in the logistic regression analysis. mNGS was confirmed as the most accurate test for PCP diagnosis in ILD patients. ILD is a new risk group of PCP with high PCP prevalence. Clinicians should pay close attention to the occurrence of PCP in ILD patients who possess the risk factors of previous glucocorticoid therapy, decreased CD4 + T cell count, increased BG level and absence of traction bronchiectasis on HRCT. mNGS showed the most excellent performance for PCP diagnosis in ILD patients. Peripheral blood CD4 + T cell count and BG level are alternative diagnostic methods for PCP in ILD patients. However, the diagnostic value of serum LDH level was limited in ILD patients.

Incidence and Outcomes of Pneumocystis Pneumonia Following Chimeric Antigen Receptor T-Cell Therapy: A Real-World Analysis

Background: Pneumocystis Pneumonia (PCP) is a known opportunistic infection after chimeric antigen receptor (CAR) T-cell therapy. However, the incidence and outcomes of PCP are poorly understood, and there has been no clear consensus on the optimal duration for PCP prophylaxis post-CAR T-cell treatment. Methods: From a large real-world database, TriNetX Research Network, we identified patients who underwent commercial anti-CD19 and anti-BCMA CAR T-cell therapy between January 2019 and January 2023. The diagnosis of PCP was established using the ICD-10-CM code B59 (pneumocystosis) or through Logical Observation Identifiers Names and Codes (LOINC) documentation of positive microbiologic tests from respiratory samples. Results: Among the 1,107 and 280 patients who received anti-CD19 and anti-BCMA CAR T-cell therapies, 19 (1.7%) and 4 (1.4%) patients developed PCP, respectively. Altogether, a total of 23 (1.7%) patients developed PCP within a median of 139 days (range 19 to 732 days) post-infusion. (Figure) Demographics, the incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the initial choice for PCP prophylaxis, were similar for patients with and without PCP. Patients who developed PCP were more likely to have used dexamethasone (65 vs 43%, p=0.02) and have a shorter duration of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis (median 9 [range 1 to 45] vs 19 [range 1 to 106] weeks, p=0.002). In the univariate analysis, patients who received TMP/SMX prophylaxis for less than 3 months showed a trend of a higher incidence of PCP compared to those who received it for more than 3 months (hazard ratio [HR] 3.54, 95% confidence interval [CI] 0.87 to 14.3, p=0.06). (Table) Regarding survival outcomes, patients with and without PCP had similar time-to-next-treatment or death (median 84 vs 68 days, HR 0.96, 95%CI 0.61 to 1.51) and overall survival (median 518 days vs not-reached, HR 1.61, 95%CI 0.91 to 2.88). Conclusions: In real-world conditions with routine prophylaxis, PCP is an infrequent opportunistic infection following anti-CD19 or anti-BCMA CAR T-cell therapy. Patients with and without PCP were associated with similar survival outcomes.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis.

Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP. Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used. Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90-0.99), and specificity was 0.96 (95% CI, 0.92-0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01-0.05) and 19.31 (95% CI, 10.26-36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78-0.99) and 0.93 (95% CI, 0.80-0.98) and a specificity of 0.96 (95% CI, 0.88-0.99) and 0.98 (95% CI, 0.76-1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90-0.98) and 0.94 (95% CI, 0.84-0.98), respectively. The overall confidence in the estimates was low. Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Study on the Prevalence of Pneumocystis jirovecii as a Causative Agent of Lung Pathology in People with Different Immune Status.

Pneumocystis pneumonia (PCP) commonly affects immunocompromised individuals, whereas in immunocompetent persons, it occurs relatively rarely, and in most cases, the Pneumocystis infection is detected as an asymptomatic colonization. The present study aimed to establish the prevalence of Pneumocystis jirovecii infection in human hosts with different immune status (immunocompromised and immunocompetent), using molecular diagnostic methods, and to compare their diagnostic value with that of classical staining methods. We used the collected-to-this-moment data from a prospective study on the prevalence of pneumocystosis among the Bulgarian population. Clinical specimens (including throat secretions, induced sputum, tracheal aspirates, and bronchoalveolar lavage) collected from 220 patients suspected of PCP (153 immunocompetent and 67 immunocompromised patients) were examined with microscopic staining methods and real-time PCR for detection of P. jirovecii. Results: DNA of the pathogen was detected in 38 (17%) specimens (32 immunocompromised patients and 6 immunocompetent subjects). From all 220 clinical samples examined by staining methods, only five (2%) P. jirovecii cysts were detected by the Gomori stain. All patients with PCP were treated with trimethoprim-sulfamethoxazole, but in ten of them (HIV-positive patients), the disease had a fatal outcome. This study is the first in Bulgaria including the main available laboratory methods for diagnosis of human pneumocystosis. Regarding the etiological diagnosis of PCP, in our study the sensitivity of real-time PCR was higher compared to the staining methods. The choice of a method for sample collection and examination has an important role in the efficiency of the laboratory diagnostics.

Evaluation of the PneumoGenius® PCR assay for the diagnosis of Pneumocystis pneumonia and the detection of Pneumocystis dihydropteroate synthase mutations in respiratory samples.

Pneumocystis pneumonia (PCP) is the most frequent fungal opportunistic infection defining AIDS in HIV-infected patients, and is of growing importance in HIV-negative patients. In this latter category of patients, the diagnosis mainly relies on real-time polymerase chain reaction (qPCR) detection of Pneumocystis jirovecii (Pj) on respiratory samples. The PneumoGenius® kit (PathoNostics) allows the simultaneous detection of Pj mitochondrial large subunit (mtLSU) and dihydropteroate synthase (DHPS) polymorphisms, which could be of interest to anticipate therapeutic failure. This study aimed at evaluating its clinical performance on 251 respiratory specimens (239 patients), (i) for P. jirovecii detection in clinical samples, and (ii) for DHPS polymorphisms detection in circulating strains. Patients were classified according to modified European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, as having proven PCP (n=62), probable PCP (n=87), Pneumocystis colonization (n=37), and no PCP (n=53). Compared with in-house qPCR, the sensitivity of PneumoGenius® assay for P. jirovecii detection reached 91.9% (182/198), the specificity was excellent (100%, 53/53) and the global concordance was 93.6% (235/253). A total of four diagnoses of proven/probable PCP were missed by the PneumoGenius® assay, reaching a 97.5% sensitivity (157/161) in this sub-group. The 12 other 'false-negative' results were obtained in patients diagnosed as colonized using the in-house PCR. DHPS genotyping was successful for 147/182 samples with PneumoGenius® and revealed dhps mutation in 8 samples, which were all confirmed by sequencing. In conclusion, PneumoGenius® assay missed the detection of low-burden PCP. This lower sensitivity for PCP diagnosis can be balanced by a higher specificity (P. jirovecii colonization less frequently detected) and the efficient detection of DHPS hot spot mutations.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients

PurposeOne of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation.Materials and methodsThis is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression.ResultsAmong the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01–1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86–0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05–40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29–53.20; p = 0.026).ConclusionPatients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Application of Metagenomic Next Generation Sequencing in the Diagnosis of Pulmonary Infectious Pathogens from Bronchoalveolar Lavage Samples in Patients Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Infection remains an important cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the impaired immune function of allo-HSCT patients, the clinical manifestations of pulmonary infection are diverse and the imaging characteristics are atypical. Meanwhile, pulmonary infections are often mixed and opportunistic pathogens are common. Therefore, diagnosis of these infections is difficult. Compared with the traditional culture method, metagenomic next-generation sequencing (mNGS) has the advantages of culture-independent, unbiased, short time-consuming and broad-spectrum detection. It is also able to detect rare and new pathogens. To further investigate the value of mNGS among allo-HSCT patients, we compared the results of mNGS of bronchoalveolar lavage (BAL) samples and microbiological culture among pulmonary infection patients after allo-HSCT. Materials and Methods: From May 28, 2018 to December 28, 2021, BAL samples were collected from 64 patients after allo-HSCT with pulmonary infection. mNGS and microbial culture of BAL were performed to evaluate the effectiveness of mNGS in the diagnosis of pulmonary infectious pathogens. Patients with disease relapse after allo-HSCT were excluded, and the follow-up was up to March 24, 2022. Results: 64 patients were enrolled in this study. The median age was 36 (17-67) years old, including 45 males (70.3%) and 19 females (29.7%), and the median time between transplantation and mNGS detection was 11.1 (0.7-91.2) months. Among 64 patients, the number of patients with only positive mNGS results was 33, 4 patients were only culture-positive, 13 patients were double negative, and 14 patients were double positive. For the double-positive group, 78.6% (11/14) of them showed completely or partly matched results. (Figure 1) In total, 47 patients (73.4%) were positive for mNGS and 18 patients (28.1%) were positive for culture, with the positive rate of mNGS higher than that of culture (p<0.01). Further analysis showed that the positive rate of fungi detected by mNGS was higher than that of culture (P = 0.043), and there was no significant difference between the positive rate of bacteria detected by mNGS and culture (P = 0.067), but the number of bacteria detected by mNGS (p=0.001) was higher than that of culture. Cytomegalovirus (CMV) (n=17) and Epstein Barr virus (EBV) (n=10) were the most commonly detected viruses in mNGS of BAL, and Pneumocystis yersini (n=13) was the most commonly detected fungus in BAL mNGS. (Figure 2) The number of Nocardia and Aspergillus fumigatus detected by BAL mNGS was higher than culture with no statistical significance. Previous the diagnosis of Pneumocystis carinii pneumonia (PCP) was based on the clinical manifestations, imaging examination, and Pneumocystis yersini detected by microscopic examination. Among 13 PCP patients, 12 patients (92.3%) had fever, cough，chest tightness，and shortness of breath, and 1 patient (7.7%) had no symptoms. 11 patients received G test, only one test result slightly exceeded the upper limit, and the other 10 tests were negative. 9 patients had typical pulmonary imaging changes of PJP, and 1 patient's CT finding of lung was consistent with the imaging findings of aspergillus pneumonia. The results showed that mNGS of BAL had advantage in the diagnosis of PCP after allo-HSCT. Conclusion: The study indicated that for patients with pulmonary infection after allo-HSCT, the positive rate of mNGS of BAL samples was higher than that of microbial culture especially for fungal infections. Furthermore, mNGS of BAL samples showed advantages over traditional methods in the detection of PCP after allo-HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P273 Diagnostic dilemmas in Pneumocystis pneumonia in case of long COVID -19

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM BackgroundTo diagnose Pneumocystis pneumonia in an underlying COVID-19 infection is difficult because of the clinical and radiological indistinguishableness of the presentation.Case PresentationWe report the case of a 67-year-old male background of type 2 diabetes mellitus (DM) and hypertension (HTN), who presented to the emergency department for severe dyspnea for 6 days. He is treated with corticosteroid and other supportive therapy. Initially, the patient responded with that treatment but suddenly his hypoxia is increasing and getting intubated. All possible causes of deterioration hypoxia were evaluated and came negative. Later stage, BAL was done and immunofluorescence test for PCP came positive. Systemic, cotrimoxazole started and gradually hypoxia improved and extubated.ConclusionPneumocystis and COVID-19 co-infection needs serious consideration, particularly for patients with long-term COVID-19, even if patients do not have conventional risk factors for Pneumocystis pneumonia.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study

BackgroundThe mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients.MethodsThis was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks.ResultsThe present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started.ConclusionsEarly ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP.Clinical trial registrationThe present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

Supplementary Role of Immunological Indicators in the Diagnosis and Prognosis of Pneumocystis Pneumonia in Non-HIV Immunocompromised Patients.

BackgroundPneumocystis pneumonia (PCP) has a high mortality in HIV-negative immunocompromised patients. The occurrence and development of PCP are believed to be correlated with the level of lymphocytes and their subsets. The aim of this study was to determine if the levels of lymphocyte subpopulations and immunoglobulin are associated with PCP.MethodsA total of 74 immunocompromised patients were enrolled in this single-center cohort study. Diagnosis of PCP was based on the relevant pulmonary symptoms and radiological imaging, and the detection of Pneumocystis jirovecii in BAL fluid or biopsy tissue by metagenomic next-generation sequencing (mNGS). All patients were divided into two groups (PCP group and non-PCP group) and the patients in PCP group were then divided into two groupsbased on the outcome of the disease during the hospitalization.ResultsWe observed a significant lower level of IgG (p=0.000) and B lymphocyte counts (p=0.017) in the PCP group comparing to that in the non-PCP group. CD4+ T cell counts, as well as the ratio of CD4+/CD8+ T cells in circulation and BAL fluid were also lower in the PCP group comparing to those in the non-PCP group. Lactate dehydrogenase (LDH) in the PCP group was significantly higher than that in the non-PCP group (p=0.029). In the PCP group, a lower level of total lymphocytes (p=0.004), T cells (p=0.001), CD4+ cells (p=0.001), and CD8+ cells (p=0.007), as well as the proportion of lymphocytes in BAL fluid (p=0.000) were found in deceased patients comparing to those in the survived group.ConclusionOur study revealed an important role of humoral immunity in the infection of Pneumocystis jirovecii. The level of B cells and IgG could be used as a supplement to predict the occurrence of PCP. The level of CD4+ and CD8+ lymphocytes was significantly correlated with the outcome of PCP.

Clinical features and prognostic predictors in patients with rheumatic diseases complicated by Pneumocystis pneumonia

To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP). Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated. A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality. A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.

Refractory flare-up of severe bronchial asthma controlled with mepolizumab due to Pneumocystis pneumonia: a case report

BackgroundBiologics dramatically improve symptoms of severe asthma; however, various exacerbating factors may induce flare-up. Pneumocystis spp. have not been reported as a cause of asthma exacerbation during biologic use, although patients with severe asthma have high levels of antibodies against Pneumocystis spp.Case presentationAn 87-year-old female with severe asthma that was well-controlled with mepolizumab, who developed a steroid-resistant refractory flare-up. Chest computed tomography showed bilateral ground glass opacities, and results of polymerase chain reaction tests on induced sputum were positive for Pneumocystis DNA. Therefore, a diagnosis of Pneumocystis pneumonia was made. The clinical symptoms improved after treatment with sulfamethoxazole–trimethoprim.ConclusionClinicians should be aware of Pneumocystis pneumonia as a cause of refractory exacerbation of bronchial asthma during use of interleukin-5 inhibitors.

Accuracy of Pneumocystis jirovecii Plasma Cell-Free DNA PCR for Noninvasive Diagnosis of Pneumocystis Pneumonia.

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is a serious infection in immunocompromised hosts which requires prompt diagnosis and treatment. The recommended specimen for diagnosis of PCP is bronchoalveolar lavage (BAL) fluid, which is invasive and may not be possible in unstable patients. The aim of this study was to evaluate the accuracy of noninvasive P. jirovecii plasma cell-free DNA (cfDNA) PCR using recently optimized preanalytical and analytical methods. Adult patients undergoing clinical testing for PCP with direct fluorescent antibody stain (DFA), respiratory PCR, and/or β-d-glucan were included in this study. Sensitivity and specificity P. jirovecii plasma cfDNA PCR was determined in PCP suspects categorized as proven and probable. A total of 149 patients were included in this study, of which 10 had proven and 27 had probable PCP. Most patients (95.9%, 143/149) were immunocompromised, including hematological malignancies (30.1%), bone marrow transplant (11.2%), solid organ transplantation (47.6%), and HIV/AIDS (4.2%). P. jirovecii plasma cfDNA PCR showed sensitivity and specificity of 100% (10/10; 95% confidence interval [CI], 69.2 to 100) and 93.4% (127/136; 95% CI, 87.8 to 96.9), and 48.6% (18/37; 95% CI, 31.9 to 65.6) and 99.1% (108/109; 95% CI, 94.9 to 100) in proven and proven/probable cases, respectively. P. jirovecii cell-free DNA PCR was similar in sensitivity but with substantially improved specificity over β-d-glucan (sensitivity, 60.0% [18/30; 95% CI, 40.6 to 77.3]); specificity, 66.7% [22/33; 95% CI, 48.2 to 82.0]) in patients with proven/probable PCP. Plasma cfDNA PCR offers a noninvasive testing option for early and accurate diagnosis of PCP, particularly in patients who cannot tolerate bronchoscopy.

Pneumocystis in the era of prophylaxis: do the guidelines have to change?

In the era of effective prophylaxis, the objective of this study was to describe pneumocystis pneumonia (PCP) patients' profile and evaluate the consistency of clinical situations encountered with the recommended indications for prophylaxis. This was a single-centre, retrospective study. All adults (> 18years) with a definitive diagnosis of PCP were included. Data were collected from patients' electronic medical files. The study examined the medical files of 225 patients diagnosed with PCP and treated between 1 January, 2015, and 30 June, 2020. More than 95% of the patients were not on anti-PCP prophylaxis at the time of PCP diagnosis. There were 32 (14%) deaths before the end of PCP treatment, mainly in auto-immune disease (30%) and solid tumours (38%) groups unlike the solid-organ transplants group, among whom deaths were infrequent. Indeed, 48% of our cohort (n = 107) had both corticosteroid (CS) therapy, immunosuppressive or immunomodulatory treatment, and lymphopaenia and could have been considered at high risk for PCP. Trimethoprim/sulfamethoxazole was administered as first-line PCP curative treatment in 95% of the patients. Toxicities of this drug led to treatment interruption in 25% of the patients (except death). This study found a high number of PCP cases over 5years. Unsurprisingly, most of the patients were immunosuppressed, with risk factors for PCP already described in the literature. This large number of PCP cases should be avoidable and, consequently, questions arise. Faced with these data, prophylaxis should be common sense for immunocompromised patients with risk factors, even if formalised recommendations do not exist.