Cases Of Pneumocystis Jirovecii Pneumonia Research Articles

Outcome of Pneumocystis Jirovecii pneumonia (PcP) in post-CAR-T patients with hematological malignancies

BackgroundPneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies.MethodsThis is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic medical record system.ResultsIn total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock.ConclusionPcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population.

Pneumocystis jirovecii pneumonia in hemato-oncological patients; 10 years of experience at Hospital Infantil Teletón de Oncología

Abstract Background Pneumocystis jirovecii pneumonia is an opportunistic infection that most frequently affects immunocompromised people, especially patients with HIV; clinical presentation is nonspecific and mortality rate in patients without HIV ranges are between 30% and 75%. In the international literature, there are few case reports of pediatric oncology patients. A series of cases is presented with the objective of describing the epidemiological characteristics, clinical presentation, treatment, and outcomes of Pneumocystis jirovecii pneumonia in this population group. Methods An observational, descriptive, and retrospective study was carried out in cancer patients under 18 years, with clinically compatible symptoms, an imaging study suggestive of the pneumonia, and identification of P. jirovecii using a PCR test of bronchial aspirate at Hospital Infantil Teletón de Oncología in Querétaro Mexico, since November 2014 to June 2023. Results A total of 17 events were reported with a median age of 9.8 years, 14/17 (82%) with a diagnosis of acute leukemias, 1/17 (6%) Ewing sarcoma, 1/17 (6%) lymphoma large cell anaplastic and 1/17 (6%) neuroblastoma. Regarding their therapeutic phases, 7/17 (41%) were in consolidation, 4/17 (23%) induction, 3/17 (18%) allogeneic HSCT (Hematopoietic stem-cell transplantation), 2/17 (12%) in surveillance, and 1/17 (6%) in maintenance. The clinical presentation in our patients was characterized by the presence of fever in 15/17 (88%), dry cough in 10/17 (59%) and 17/17 (100%) developed acute respiratory distress syndrome, which was classified as mild in 7/17 (41%), moderate in 5/17 (29%) and severe in 5/17 (29%). 13/17 (75%) presented distributive shock. All our patients underwent chest x-rays, 12/17 (70.5%) presented bilateral interstitial infiltrate, 4/17 (23.5%) consolidation, and 1/17 (6%) pleural effusion. Lung CT (computed tomography) was performed in 4/17 (23.5%), and 4/4 (100%) presented ground glass opacities. All of our patients were admitted to the PICU (Pediatric intensive care unit) and 16/17 (94%) required invasive mechanical ventilation. All receive treatment with TMP-SMX (Trimethoprim-sulfamethoxazole). 4/17 patients died (23%) of whom none received prophylaxis. 3/17 patients (18%) received prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Conclusion The present study is the first study in Mexico that compiles cases of Pneumocystis Jirovecii pneumonia in pediatric oncology patients. P. jirovecii pneumonia remains a rare cause, but represents a potentially fatal cause in oncology patients, so it is important to have a high clinical suspicion during the evaluation of an immunocompromised patient with evidence of pneumonia during all treatment phases with chemotherapy, in order to start treatment promptly. Thus, we also emphasize the importance of adequate prophylaxis as the most important preventive measure.

The Prevalence, Predisposing Factors, and Outcomes of Pneumocystis jirovecii Pneumonia among Pediatric Inpatients, Northeastern Iran

Abstract Objective Pneumocystis jirovecii pneumonia (PJP), caused by Pneumocystis jirovecii, is one of the opportunistic fungal infections that can cause life-threatening pneumonia in children with underlying diseases. Due to the similarity of the symptoms of PJP with other lung infections, such as tuberculosis, differential and accurate diagnosis is necessary. The current study investigated the molecular diagnosis of P. jirovecii, predisposing factors and the outcomes, among pediatric inpatients in Northeastern Iran. Methods In this study, 180 bronchoalveolar lavage specimens were obtained from hospitalized children with respiratory disorders. The specimens were examined using Giemsa stain, and the genomic DNA was extracted according to the protocol of the AmpliSens kit. A real-time polymerase chain reaction (PCR) technique was used to detect P. jirovecii by the AmpliSens Pneumocystis jirovecii (carinii)-FRT PCR kit. Results Among the patients studied, 34 (18.9%) were positive and 8 (4.4%) were suspicious of the presence of P. jirovecii. Among the 34 positive cases, 12 (35%) were diagnosed before, and 22 (65%) during the coronavirus 2019 (COVID-19) pandemic. Only two cases (5.88%) among the positive ones detected by the real-time PCR method were observed using Giemsa staining. Also, no correlation was observed between positive cases of infection and the sex, the outcomes, and underlying diseases. Conclusion The results showed that PJP has a relatively high prevalence among pediatric inpatients with respiratory disorders. Neutropenia is a significant predisposing factor in these patients. However, there is no correlation between PJP cases and outcomes and underlying diseases. Most of the patients with PJP were affected during the COVID-19 pandemic, probably due to treatment with corticosteroids.

Predictive models-assisted diagnosis of AIDS-associated Pneumocystis jirovecii pneumonia in the emergency room, based on clinical, laboratory, and radiological data.

We assessed predictive models (PMs) for diagnosing Pneumocystis jirovecii pneumonia (PCP) in AIDS patients seen in the emergency room (ER), aiming to guide empirical treatment decisions. Data from suspected PCP cases among AIDS patients were gathered prospectively at a reference hospital's ER, with diagnoses later confirmed through sputum PCR analysis. We compared clinical, laboratory, and radiological data between PCP and non-PCP groups, using the Boruta algorithm to confirm significant differences. We evaluated ten PMs tailored for various ERs resource levels to diagnose PCP. Four scenarios were created, two based on X-ray findings (diffuse interstitial infiltrate) and two on CT scans ("ground-glass"), incorporating mandatory variables: lactate dehydrogenase, O2sat, C-reactive protein, respiratory rate (> 24bpm), and dry cough. We also assessed HIV viral load and CD4 cell count. Among the 86 patients in the study, each model considered either 6 or 8 parameters, depending on the scenario. Many models performed well, with accuracy, precision, recall, and AUC scores > 0.8. Notably, nearest neighbor and naïve Bayes excelled (scores > 0.9) in specific scenarios. Surprisingly, HIV viral load and CD4 cell count did not improve model performance. In conclusion, ER-based PMs using readily available data can significantly aid PCP treatment decisions in AIDS patients.

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

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. 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. 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. The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.

Metagenomic Next-Generation Sequencing for Accurate Diagnosis of Pneumocystis jirovecii Pneumonia: A Comparative Study with Traditional Methods.

Metagenomic next-generation sequencing (mNGS) is a high-throughput sequencing technique that identifies a wide array of pathogens directly from clinical specimens. This study evaluates the diagnostic value of mNGS in Pneumocystis jirovecii pneumonia (PJP) and compares its efficacy with traditional detection methods, including Grocott's Methenamine Silver (GMS) staining, serum (1-3)-β-D-Glucan (BDG) testing, and Lactate Dehydrogenase (LDH) testing. Seventy-eight patients hospitalized between January 2022 and March 2023 with suspected pulmonary infections were included. Patients were eligible for mNGS if they exhibited symptoms such as fever, cough, dyspnea, or progressive hypoxemia, and met specific clinical criteria for PJP. Specimens obtained included bronchoalveolar lavage fluid, sputum, and peripheral blood. Positive rates and pathogen distributions detected by mNGS and traditional methods were compared. In the PJP group, 25%, 37.5%, and 9.38% of patients had solid organ tumors, corticosteroid use, and skin diseases, respectively, significantly higher than in the non-PJP group. The sensitivity and specificity of mNGS were both 100%, significantly higher than those of serum BDG (sensitivity 50%, specificity 81.8%) and LDH (sensitivity 9.3%, specificity 91.3%). Significant differences in microbial composition between the PJP and Non-PJP groups were observed. mNGS detected multiple mixed pathogens in 96.88% of PJP cases, with 68.75% exhibiting mixed bacterial and viral infections. Notably, 71% of patients improved following antibacterial treatment based on mNGS results. mNGS technology shows superior sensitivity and specificity in diagnosing PJP and guides precise treatment for complex pulmonary infections.

Risk Factors of Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.

: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. : This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. : During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. : PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.

Validity of claims-based diagnoses for infectious diseases common among immunocompromised patients in Japan

BackgroundTo validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP).MethodsVALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012–2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases.ResultsOf patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4–70.5% (HZ), 67.0–90.0% (MTB), 18.3–63.4% (NTM), and 20.0–45.0% (PJP) for prevalent cases, and 69.1–70.9% (HZ), 58.6–87.9% (MTB), 10.0–56.0% (NTM), and 22.6–51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM.ConclusionsVALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.

Risk-benefit analysis of primary prophylaxis against Pneumocystis jirovecii pneumonia in patients with rheumatic diseases receiving rituximab.

To identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) outweighs the risk of adverse events (AEs) METHODS: This study included 818 patients treated with rituximab for rheumatic diseases. Of these, 419 received prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) with rituximab while the remainder did not. Differences in 1-year PJP incidence between the groups were estimated using Cox regression. Risk-benefit assessment was performed in the subgroup stratified according to risk factors based on the number needed to treat (NNT) to prevent one case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication. During the 663.1 person-years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high-dose glucocorticoids (≥30mg/day of prednisone during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person-years) was 7.93 (2.91-17.25) in the subgroup receiving high-dose glucocorticoids, compared with 0.40 (0.01-2.25) in the subgroup without high-dose glucocorticoids. Although prophylactic TMP-SMX significantly reduced the overall PJP incidence (HR 0.11 [0.03-0.37]), the NNT to prevent one PJP was higher than the NNH (146 vs. 86). In contrast, the NNT fell to 20 (10.7-65.7) in patients receiving concomitant high-dose glucocorticoids. The benefit associated with primary PJP prophylaxis overweighs the risk of severe AEs in patients receiving rituximab and concomitant high-dose glucocorticoid treatment. This article is protected by copyright. All rights reserved.

Risk Factors for Pneumocystis jirovecii Pneumonia in Non-HIV Patients Hospitalized for COVID-19: A Case-Control Study.

Very few cases of Pneumocystis jirovecii pneumonia (PJP) have been reported in COVID-19 so far, and mostly in patients with concomitant HIV infection or in solid-organ transplant recipients. Despite COVID-19 being associated with lymphopenia and the use of steroids, there are no studies specifically aimed at investigating the risk factors for PJP in COVID-19. A retrospective case-control study was performed. We matched PJP cases with controls with a 1:2 ratio, based on age ± 10 years, solid-organ transplantation (SOT), hematological malignancies, and in the setting of PJP development (ICU vs. non-ICU). A direct immunofluorescence assay on bronchoalveolar lavage fluid was used to diagnose PJP. We enrolled 54 patients. Among 18 cases of PJP, 16 were diagnosed as "proven". Seven of the eighteen cases were immunocompromised, while the other patients had no previous immunological impairment. Patients with PJP had significantly lower median lymphocyte values (p = 0.033), longer COVID-19 duration (p = 0.014), a higher dose of steroid received (p = 0.026), higher CRP values (p = 0.005), and a lower SARS-CoV-2 vaccination rate than the controls (p = 0.029). Cumulative steroid dose is the independent risk factor for PJP development (OR = 1.004, 95%CI = 1-1.008, p = 0.042). PJP develops in COVID-19 patients regardless of immunosuppressive conditions and the severity of disease, and it is correlated to the corticosteroid dose received.

Outcome of glioblastoma patients after intensive care unit admission with invasive mechanical ventilation: a multicenter analysis

PurposePatients with glioblastoma are exposed to severe symptoms and organs failures (e.g., coma or acute respiratory failure), that may require intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). However, only limited data are available concerning the prognosis of patients with glioblastoma receiving IMV. We sought to describe the reasons for ICU admission, and outcomes of patients with glioblastoma requiring IMV for unplanned critical complications.MethodsIn this retrospective analysis, four certified interdisciplinary brain tumor centers performed a retrospective review of their electronic data systems. All patients with glioblastoma admitted to an in-house ICU and receiving IMV between January 2015 and December 2019 were included. Clinical and prognostic factors as well as relevant outcome parameters were evaluated by group comparisons and Kaplan Meier survival curves.ResultsWe identified 33 glioblastoma patients with a duration of IMV of 9.2 ± 9.4 days. Main reasons for ICU admission were infection (n = 12; 34.3%) including 3 cases of Pneumocystis jirovecii pneumonia, status epilepticus (31.4%) and elevated intracranial pressure (22.9%). In-hospital mortality reached 60.6%. Younger age, low number of IMV days, better Karnofsky Performance Status Scale before admission and elevated intracranial pressure as cause of ICU admission were associated with positive prognostic outcome.ConclusionWe conclude that less than 50% of patients with glioblastoma have a favorable short-term outcome when unplanned ICU treatment with IMV is required. Our data mandate a careful therapy guidance and frequent reassessment of goals during ICU stay.

Lung Epithelial Cell Line Immune Responses to Pneumocystis.

Pneumocystis sp. are fungal pathogens and members of the Ascomycota phylum. Immunocompetent individuals can readily eliminate the fungus, whereas immunocompromised individuals can develop Pneumocystis jirovecii pneumonia (PJP). Currently, over 500,000 cases occur worldwide, and the organism is listed on the recently released WHO fungal priority pathogens list. Overall, the number of PJP cases over the last few decades in developed countries with the use of highly effective antiretroviral therapy has decreased, but the cases of non-HIV individuals using immunosuppressive therapies have significantly increased. Even with relatively effective current anti-Pneumocystis therapies, the mortality rate remains 30-60% in non-HIV patients and 10-20% during initial episodes of PJP in HIV/AIDS patients. Although the role of alveolar macrophages is well studied and established, there is also well-established and emerging evidence regarding the role of epithelial cells in the immune response to fungi. This mini review provides a brief overview summarizing the innate immune response of the lung epithelium and various continuously cultured mammalian cell lines to Pneumocystis.

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder.

Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count<.5×109 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p=.014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p<.001). PJP was associated with mortality within 90days of diagnosis (p<.001), but not after 90days (p=.317). PJP was also associated with 90-day death-censored renal allograft loss (p=.026). PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90days. PJP prophylaxis should be considered in SOT recipients with PTLD.

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.

Risk factors for late-onset Pneumocystis jirovecii pneumonia in liver transplant recipients

ObjectivesThe risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis. MethodsAmong 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP. ResultsAfter 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP. ConclusionLate-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication.

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.

Pneumocystis jirovecii pneumonia associated with immune checkpoint inhibitors: A systematic literature review of published case reports and disproportionality analysis based on the FAERS database.

Background: Pneumocystis jirovecii pneumonia (PJP) has been reported with ICIs but limited to case reports. The clinical features of PJP with ICIs remain mostly unknown. This study aims to investigate the association of PJP with ICIs and describe clinical features. Methods: Reports of PJP recorded in FAERS (January 2004-December 2022) were identified through the preferred term "Pneumocystis jirovecii pneumonia". Demographic and clinical features were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC), using traditional chemotherapy and targeted therapy as comparators, and adjusting signals by excluding contaminant immunosuppressive drugs and pre-existing diseases. A systematic literature review was conducted to describe clinical features of published PJP reports with ICIs. Bradford Hill criteria was adopted for global assessment of the evidence. Results: We identified 677 reports of PJP associated with ICIs, in which 300 (44.3%) PJP cases with fatal outcome. Nivolumab (IC025 2.05), pembrolizumab (IC025 1.88), ipilimumab (IC025 1.43), atezolizumab (IC025 0.36), durvalumab (IC025 1.65), nivolumab plus ipilimumab (IC025 1.59) have significant signals compared to other drugs in FAERS database. After excluding pre-existing diseases and immunosuppressive agents which may increase susceptibility of PJP, the signals for PJP associated with nivolumab, pembrolizumab, durvalumab, nivolumab plus ipilimumab remained robust (IC025 > 0). When compared to other anticancer regimens, although all ICIs showed a lower disproportionate signal for PJP than chemotherapy, nivolumab (IC025 0.33, p < 0.001), pembrolizumab (IC025 0.16, p < 0.001), both PD-1 inhibitors, presented a higher signal for PJP than targeted therapy. Male gender (IC025 0.26, p < 0.001) and age >65years (IC025 0.38, p < 0.001) were predominant in PJP cases associated with across all ICIs. In literature, 15 PJP cases associated with ICIs were reported in 10 published case reports. 12 of 15 (80.0%) of cases received PD-1 inhibitors before PJP was diagnosed. Conclusion: By the combined analysis of post-marketing data from FAERS and published case reports, we identified ICIs may be associated with PJP, especially in males aged >65years. After accounting for confounders, PD-1 inhibitors emerged with a robust disproportionality signal when compared to PD-L1/CTLA-4 inhibitors as well as targeted therapy. Further research is warranted to validate our findings.

Clinical Impact of Noninvasive Plasma Microbial Cell-Free Deoxyribonucleic Acid Sequencing for the Diagnosis and Management of Pneumocystis jirovecii Pneumonia: A Single-Center Retrospective Study.

We present 23 cases of Pneumocystis jirovecii pneumonia (PCP) diagnosed with commercially available noninvasive plasma microbial cell-free deoxyribonucleic acid (mcfDNA) assay. Our findings suggest that plasma mcfDNA testing resulted in positive clinical impact for the diagnosis and treatment of PCP and coinfections in 82.6% of cases.

Rates of Pneumocystis jirovecii pneumonia and prophylaxis prescribing patterns in a large electronic health record cohort of patients with systemic lupus erythematosus

Objective No guidelines exist for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in patients with systemic lupus erythematosus (SLE). Limited data are available on incidence of PJP infection and use of PJP prophylaxis. Using a real-world, electronic health record (EHR) cohort, we investigated the frequency of PJP infections as well as patient and provider factors that impacted use and type of PJP prophylaxis.Methods In a large, de-identified EHR, we identified possible SLE patients using a previously validated algorithm. PJP ICD-9 or ICD-10-CM billing codes and PJP keywords were used to identify possible PJP cases within this SLE cohort. We assessed for PJP prophylaxis prescribing in all SLE patients using keywords and reviewing medication lists for prophylactic agents. Chart review was used to confirm cases of SLE, PJP, and PJP prophylaxis and to obtain data on demographics, comorbidities, and immunosuppressants.Results Of 977 SLE patients, there were only four with confirmed PJP infection. Two of these patients had concurrent Acquired Immunodeficiency Syndrome, and none were on prophylaxis. Of 977 SLE patients, 132 (14%) were prescribed PJP prophylaxis. Of 617 SLE patients ever prescribed immunosuppressants, 128 (21%) were prescribed PJP prophylaxis. Sulfonamides were the most common prophylaxis prescribed (69%), and possible adverse events were documented in 22 out of 117 instances of being placed on a sulfonamide. Patients of younger age, Black race, nephritis, and renal transplant, and on chronic glucocorticoids were all more likely to have PJP prophylaxis prescribed. Patients who were on transplant induction medications, calcineurin/mTOR inhibitors, cyclophosphamide, and mycophenolate mofetil all were more likely to be prescribed PJP prophylaxis compared to other immunosuppressants.Conclusion PJP is a rare diagnosis among SLE patients, and prior studies may even overestimate its prevalence. PJP prophylaxis was less common in our cohort than previously described. Adverse events related to sulfonamides used for PJP prophylaxis were relatively rare with lower rates than previously reported. Our study demonstrates real-world PJP prophylaxis prescribing patterns in a large cohort of SLE patients.

Prophylactic effect of low-dose trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia in adult recipients of kidney transplantation: a real-world data study

ObjectivesTo evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation. MethodsThree kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function. ResultsAmong the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001). ConclusionLow-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.