Pneumocystis Carinii Pneumonia Research Articles

Localized Pneumocystis jirovecii pneumonia in a malnourished, non-HIV-infected man in the absence of any established or diagnosed immunosuppressive condition: a case report

BackgroundPneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings.Case presentationA 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung.ConclusionsPJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions.

Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital.

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ± 15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9-8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up.

B-204 A Real-time Probe-based PCR Assay for Detection of Pneumocystis Pneumonia

Abstract Background Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that continues to be one of the major opportunistic pathogens causing severe Pneumocystis pneumonia (PcP) in individuals with acquired immune deficiency syndrome (AIDS) and patients with immunosuppression due to other causes. Widespread prophylaxis and treatment for P. jirovecii with sulfa drugs have decreased the incidence of PcP, but concerns have been raised about the possible emergence of P. jirovecii isolates resistant to these drugs. Point mutations in this gene have been associated with prior exposure to sulfa drugs in other microorganisms, the polymorphic positions 165 and 171, which lead to an amino acid change at positions 55 (Thr55Ala) and 57 (Pro57Ser) of the polypeptide chain, respectively. Fluorescent PCR technology can detect the nucleic acid fragments of P. jirovecii in patients' serum, alveolar perfusion fluid (BALF) and tissue samples, and further identify drug-resistant mutations, which is of great significance for early clinical and accurate initiation of antifungal therapy. MycoMDx Pneumocystis Jirovecii PCR Assay is the use of PCR-fluorescence probe method, combined with other methods to achieve the auxiliary diagnosis of P. jirovecii infection and resistance to sulfonamides (Fig. 1). Methods In this study, we did a performance evaluation of the MycoMDx Pneumocystis Jirovecii PCR Assay (CE-approved), including diagnostic sensitivity and specificity, the limit of detection (LoD), precision and stability. The above PCR assay reagents were developed and produced by Dynamiker Biotechnology (Tianjin) Co., Ltd. Results The sensitivity and specificity of the PCR assay reagents were above 90%, the LoD was 1000 copies/mL, and the precision and stability were in accordance with the requirements (CV≤5%). Conclusions The MycoMDx Pneumocystis Jirovecii PCR Assay has great clinical value by providing a rapid and reliable test to aid in early diagnosis.

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study

ObjectivesLow-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. MethodsThis retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0–20.0 mg/kg/d) and low-dose (7.5–15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. ResultsAmong 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, −1.4 %; 95 % CI, −4.5–1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3–6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, −4.0 %; 95 % CI, −7.4 to −0.6 %; P = 0.020). ConclusionLow-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

The Differential Diagnostic Value of Chest Computed Tomography for the Identification of Pathogens Causing Pulmonary Infections in Patients with Hematological Malignancies.

The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections. Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed. Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2-4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients. CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients. Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.

Impact of a trainee-led initiative to address PCP prophylaxis barriers.

319 Background: In a prior trainee-led QI initiative, we surveyed clinicians about Pneumocystis pneumonia (PCP) and assessed rates of appropriate prophylaxis. Through retrospective chart review, we found that 47% of eligible patients (n=140/297) received PCP prophylaxis between 5/2022 and 5/2023. Clinician-reported barriers included knowledge gaps, systems-related gaps, and unclear corticosteroid durations. In the current initiative, we built an order set to facilitate PCP prophylaxis prescription and created an automated approach to assess prophylaxis rates. We then re-evaluated perceived barriers to prescribing PCP prophylaxis. Methods: A multidisciplinary team of oncology fellows and QI staff was established at Johns Hopkins. A new PCP prophylaxis order set was implemented on 4/15/2023. An automated data query was developed to identify patients with solid malignancies who were eligible for PCP prophylaxis per ASCO/IDSA guidelines (≥20mg prednisone equivalents daily for ≥1 month). Patient data was collected between 4/15/2022 and 4/15/2024. Surveys were conducted in 5/2023 and 5/2024 to assess prescriber knowledge of, and attitudes toward, PCP prophylaxis. The survey was open to prescribers across oncology specialties. Results: 1,404 patients were eligible for PCP prophylaxis over the 2-year study period, with 19% (n=264) receiving prophylaxis. In the year before the order set, 21% (n=138) of eligible patients were prescribed prophylaxis. In the year after the order set, 17% (n=126) of eligible patients were prescribed prophylaxis. A survey conducted post order set implementation included 52 responses from 42% (n= 22) attending physicians, 35% (n=18) advanced practice providers, and 23% (n=12) residents/fellows. While 92% (n=48) of survey participants had prescribed PCP prophylaxis, 31% (n=16) knew the dose/duration of corticosteroids at which society guidelines recommend prophylaxis. Unclear corticosteroid duration, guideline knowledge, and concern about side-effects were the most commonly reported barriers to prescribing prophylaxis. Conclusions: Compared to the prior chart review approach, the automated query identified more than twice as many patients at risk for PCP. Strikingly, &lt;25% of eligible patients were prescribed PCP prophylaxis. Prescription rates did not improve following implementation of the order set. However, the post order set survey found increased rates of guideline knowledge and identified unclear corticosteroid durations as the primary barrier to prophylaxis. Building on these findings, an additional PDSA cycle is ongoing including development of notification system alerting providers when PCP prophylaxis is recommended for their patients. Barriers to PCP prophylaxis. Barrier Number of Respondents (%) Pre Order Set Number of Respondents (%) Post Order Set Unclear Corticosteroid Duration 8 (11%) 10 (19%) Guideline Knowledge 11 (16%) 7 (13%) Lack of EMR Notification 6 (9%) 2 (4%)

Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study.

Few treatment options exist for patients with non-Hodgkin lymphoma, and outcomes remain poor for relapsed or refractory disease. We evaluated the safety and preliminary clinical activity of valemetostat, a novel inhibitor of EZH2 and EZH1, in patients with relapsed or refractory non-Hodgkin lymphomas. This first-in-human, multicentre, open-label, single-arm, phase 1, dose-escalation and dose-expansion trial was done in 19 hospitals across Japan and the USA. Patients were included if they were aged 18 years or older in the USA or 20 years or older in Japan with a primary diagnosis of relapsed or refractory non-Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. In the dose-escalation part, patients received oral valemetostat at doses of 150 mg per day, 200 mg per day, 250 mg per day, and 300 mg per day continuously in 28-day cycles until progressive disease or unacceptable toxicities. All patients received 200 mg per day in the dose-expansion part. The primary endpoints were safety, pharmacokinetics, and the recommended phase 2 dose; the secondary endpoints were the maximum tolerated dose and the antitumour activity of valemetostat. Responses were assessed in patients who received at least one dose, with measurable lesions at baseline according to the International Working Group 2007 revised criteria for malignant lymphoma (peripheral T-cell lymphoma and B-cell non-Hodgkin lymphoma) and the modified 2009 criteria for adult T-cell leukaemia/lymphoma. The trial is registered with ClinicalTrials.gov, NCT02732275, and is currently active, but not recruiting. Between April 7, 2016, and June 10, 2021, 90 patients (53 [59%] males and 37 [41%] females; 49 [54%] Asian, 33 [37%] White, and eight [9%] Black) were enrolled and treated with valemetostat and included in the safety analysis set. 57 (63%) patients had peripheral T-cell lymphoma, 14 (16%) had adult T-cell leukaemia/lymphoma, and 19 (21%) had B-cell non-Hodgkin lymphoma. Seven (8%) patients received valemetostat 150 mg per day, 74 (82%) received 200 mg per day, seven received 250 mg per day, and two received 300 mg per day. Median follow-up was 7·4 months (IQR 3·4-17·6). All patients had at least one treatment-emergent adverse event; the most common treatment-emergent adverse events of any grade were decreased platelet count (52 [58%] of 90 patients), dysgeusia (45 [50%]), and anaemia (38 [42%]). The most common grade 3-4 adverse events were decreased neutrophil count (21 [23%]), decreased platelet count (18 [20%]), and decreased lymphocyte count (17 [19%]). The most common serious adverse event of any grade was Pneumocystis jirovecii pneumonia (four [4%]). No treatment-related deaths occurred. The overall response rate was 54·5% (48 of 88; 95% CI 43·6-65·2) for patients in the efficacy analysis set. The maximum tolerated dose was not reached; the recommended phase 2 dose of 200 mg per day was determined. Valemetostat exposure was variable between patients and was overlapped over the dose range of 150-250 mg per day. The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. Favourable clinical activity was observed. These findings support a new indication for valemetostat in this setting. Daiichi Sankyo.

Usefulness of Serum (1, 3) Beta D Glucan in Diagnosis of Pneumocystis Jirovecii Pneumonia in Immunocompromised Patients

Usefulness of Serum (1, 3) Beta D Glucan in Diagnosis of Pneumocystis Jirovecii Pneumonia in Immunocompromised Patients

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

Efficacy and safety of a low-dose sulfamethoxazole/trimethoprim regimen in preventing pneumocystis pneumonia: A retrospective study using a large-scale electronic medical record database

IntroductionSulfamethoxazole/trimethoprim (ST) is a first-line drug for preventing pneumocystis pneumonia (PCP). Several small-scale studies have suggested the usefulness of the low-dose regimen of ST (200/40 mg/day) over the standard-dose one (400/80 mg/day). Thus, this study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in preventing PCP in patients with non human immunodeficiency virus infection using a large-scale electronic medical record database. MethodsThis retrospective study included patients who received ST prophylaxis for PCP registered in the RWD database between June 2007 and February 2023. Patients received either standard-dose (400/80 mg/day) or low-dose (200/40 mg/day) regimen groups. The incidence of cases initiated PCP therapeutic dose (ci-PCPTD) (ST ≥ 3600/720 mg/day) and adverse events (AEs) was evaluated, and risk factors for ci-PCPTD were investigated. ResultsA total of 11,384 patients received the standard-dose, whereas 7973 received the low-dose regimen groups. No significant difference in the cumulative incidence of ci-PCPTD was observed between the standard-dose (0.67%) and low-dose regimen group (0.47%). Lung disease was a significant risk factor for ci-PCPTD. The cumulative incidence of ci-PCPTD in patients with acute exacerbation of interstitial pneumonia was 1.3% in both groups, and no significant difference was observed between the two groups. The low-dose regimen group had a lower incidence of all AEs than the standard-dose regimen group. ConclusionThese results based on a large-scale electronic medical record database provide important evidence supporting the clinical significance of low-dose regimen of ST.

Diagnosis and treatment of pneumocystis pneumonia - a review article

This study aims to comprehensively evaluate the literature on recent advances in the diagnosis and treatment of Pneumocystis Pneumonia (PCP). A thorough review of relevant literature was conducted. Data were sourced from electronic databases such as PubMed, Scopus, Google Scholar, and Medline, focusing on articles published within the last ten years. The review included 41 articles. The diagnosis of PCP has evolved with the development of molecular techniques, advanced imaging modalities, and artificial intelligence models. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the mainstay of treatment. Corticosteroid adjunctive therapy (CAT) has demonstrated efficacy in improving outcomes, while emerging research suggests a potential role for immunomodulatory agents. Chemoprophylaxis with TMP-SMX remains the main stay of prevention in populations at risk. Despite advances in diagnostic technologies, treatment options for PCP have largely remained unchanged. There are currently no vaccines, and chemoprophylaxis remains the mainstay of prevention. Practical Immediate treatment is essential. New ELISA techniques are viable, while real-time PCR proves superior to nested PCR. Clinical judgment plays a critical role in supporting laboratory diagnoses. High-resolution CT scans may be warranted for evaluating immunosuppressed patients with suspected pneumonia when chest X-rays appear normal. Radiomics can assist in distinguishing PCP from other types of pneumonia in non-HIV patients. Trimethoprim-sulfamethoxazole remains the preferred treatment, with alternative options including dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Corticosteroid adjunct therapy (CAT) is beneficial in treating PCP, and chemoprophylaxis is essential for high-risk populations.

Development of a clinical risk score for the prediction of Pneumocystis jirovecii pneumonia in hospitalised patients

BackgroundThe performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP.MethodsThe score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score’s receiver operating characteristic curve.ResultsParticipants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty.ConclusionWe propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Prognostic analysis of Pneumocystis jirovecii pneumonia in patients with systemic vasculitides: a retrospective cohort study

ObjectivesPneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors.MethodData on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared.ResultsAmong 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD.ConclusionsMPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.Key Points• Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients.• Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis.• In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.

Identifying optimal serum 1,3-β-D-Glucan cut-off for diagnosing Pneumocystis Jirovecii Pneumonia in non-HIV patients in the intensive care unit

BackgroundSerum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population.MethodsThis retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs.ResultsOf 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10–9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03–93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden’s index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV.ConclusionsTailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG’s diagnostic performance in the ICU settings.

Progress on nonculture based diagnostic tests for invasive mould infection.

This review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods. There has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development. Rapid and low through-put B-D-Glucan assays increase access to testing and there has been significant progress in the standardization/development of molecular tests. Despite this, no single perfect test exists and combining tests (e.g., antigen and molecular testing) is likely required for the optimal diagnosis of most fungal diseases. Based on established clinical performance few mycological tests can be used alone for optimal diagnosis of fungal disease (FD) and combining tests, including classical approaches is the preferred route for confirming and excluding disease. Next-generation sequencing will likely play an increasing role in how we diagnose disease, but optimization, standardization and validation of the entire molecular process is needed and we must consider how host biomarkers can stratify risk. Given the burden of FD in low- and medium-income countries, improved access to novel but more so existing diagnostic testing is critical along with simplification of testing processes.

Comparison of High-Dose versus Low-Dose Trimethoprim-Sulfamethoxazole for Treating Pneumocystis jirovecii Pneumonia among Hemodialysis Patients: A Nationwide Database Study in Japan.

Background: Hemodialysis patients are at high risk for developing Pneumocystis jirovecii pneumonia (PJP), and trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for treating this disease. However, there is a lack of consensus on the required dosage of TMP-SMX for hemodialysis patients. Methods: This study used the nationwide Japanese Diagnosis Procedure Combination database to review hemodialysis patients hospitalized for PJP from April 2014 to March 2022. Eligible patients were divided into high-dose and low-dose groups based on the median daily dose per body weight of TMP. The 90-day mortality and adverse events after propensity score matching were compared between the groups. Results: A total of 126 hemodialysis patients with PJP were included, and the median daily dose per body weight of TMP was 5.74 mg/kg/day (interquartile range: 4.33-8.18 mg/kg/day). Thirty-two pairs were analyzed after the propensity score matching. No significant differences in the 90-day mortality and proportion of adverse events were observed between the high-dose and low-dose groups. Conclusions: A high dose of TMP-SMX is unlikely to decrease the in-hospital mortality and adverse events among hemodialysis patients with PJP. However, the results should be interpreted with caution, given the lack of power and lack of long-term follow-up. Additional prospective interventional studies are required to validate these results.

Clinical features of 20 cases with Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation

This study included 20 patients with hematological diseases who developed Pneumocystis jirovecii pneumonia (PJP) after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from April 2014 to October 2022 at Peking University People's Hospital. The 20 patients comprised 13 males (65.0% ) and seven females (35.0% ), with a median age of 34 (19-60) years. Eleven cases (55.0% ) of acute myeloid leukemia, four cases (20.0% ) of acute lymphocytic leukemia, two cases (10.0% ) of myelodysplastic syndrome, one case (5.0% ) of chronic myelomonocytic leukemia, one case (5.0% ) of non-Hodgkin lymphoma, and one case (5.0% ) of aplastic anemia were analyzed. Three cases (15.0% ) of HLA-identical sibling hematopoietic stem cell transplantation, three cases (15.0% ) of matched unrelated donor hematopoietic stem cell transplantation, and 14 cases (70.0% ) of haploid hematopoietic stem cell transplantation were identified. The median onset time of PJP was 353 (74-1121) days after transplantation. The clinical symptoms mainly included fever, cough, expectoration, and dyspnea. All patients presented signs of infection based on the CT scan, including bilateral diffuse ground-glass opacities, patchy shadows, and solid nodules. Nine patients (45.0% ) required respiratory support via nasal catheter oxygen inhalation, while seven patients (35.0% ) required ventilator-assisted breathing. Seven (35.0% ) severe infections and 13 (65.0% ) mild to moderate infections were recorded. Moreover, eight patients (40.0% ) were complicated with human cytomegalovirus infection, whereas two patients were complicated with EB virus infection. Furthermore, all 20 patients received treatment with compound sulfamethoxazole (standard dose, 11 cases; low dose, 9 cases). Furthermore, 19 patients survived and one patient died.

A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Setting.

Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS). This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS. This is a chart review from the MS registry maintained at the institute from a University Hospital in South India. Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae. Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.

Infective pulmonary diseases and the eye: a narrative review.

Several infectious pulmonary diseases affect the eye. An understanding of the association between infectious pulmonary and ocular diseases is pivotal to their successful management. We aimed to review the infections affecting both the lungs and the eye. The electronic database PubMed and the search engine Google Scholar were searched for relevant articles. Ocular tuberculosis (TB), usually not associated with clinical evidence of pulmonary TB, can affect almost all the ocular structures. Confirmation of the diagnosis of ocular TB requires demonstration of Mycobacterium tuberculosis in ocular fluids/tissues. Among the drugs used to treat TB, ethambutol, isoniazid, and linezolid may cause toxic optic neuropathy. Elderly, those with renal disease, diabetes mellitus, malnourished, alcoholics, and those who will receive ethambutol at doses greater than 15 mg/kg/day and for prolonged periods are at high risk of developing toxic optic neuropathy. These individuals should be referred to an ophthalmologist before initiating ATT for a baseline ophthalmic evaluation. Linezolid may also cause toxic retinal neuropathy. Rifampicin may cause yellowish-orange discoloration of tears and contact lenses. Adenovirus, coronavirus, influenza virus, respiratory syncytial virus, and rhinovirus exhibit both pulmonary and ocular tropism. Pneumocystis jirovecii choroiditis is rare and mainly seen when aerosolized pentamidine is used for pneumocystis pneumonia prophylaxis. Further research is needed to develop non-interventional strategies to diagnose ocular TB. Biomarkers for early detection of toxic optic neuropathy are a need of the hour. Genetic factors and mechanisms behind the development of ethambutol, isoniazid, and linezolid-induced toxic optic neuropathy need further study.

Features of the clinical course of the new coronavirus infection in HIV-infected patients

The aim. To study the features of the clinical course of a new coronavirus infection in patients infected with HIV.Materials and methods. The study included patients with HIV infection who received inpatient care for a new coronavirus infection (n=118). The diagnosis of U07.1 was made by detecting SARS-CoV-2 RNA. The diagnosis of U07.2 was made on the basis of epidemiological and clinical data in the presence of antibodies to SARS-CoV-2 in the blood.Results and discussion. The overall cohort of patients was dominated by women (55,9%), the average age of all co-infected patients was 37,5±2,78 years. The study was dominated by patients with a long history of HIV infection (66,1%), 43,2% received antiretroviral therapy (ART). The new coronavirus infection had a moderate course in 75,4% of patients. Severe form was recorded in 16,9% of patients. The mortality rate was 12,7%. The clinical picture of the new coronavirus infection upon admission was very variable due to comorbid pathology. The most frequently recorded symptoms upon admission were: increased body temperature (100%); weakness and increased fatigue (94,8%); cough (83,9%); shortness of breath (75,4%). Less frequently recorded: rhinorrhea (54,2%); sore throat (44,1%); gastrointestinal syndrome (21,2%); cerebral syndrome (17,8%); edematous-ascitic syndrome (13,5%); hepatolienal syndrome (13,5%); exanthema syndrome (10,2%). In 28,7% of patients, the number of CD4 lymphocytes was less than 200 cells/ml. The average level of CD4 lymphocytes was 321,3±43,6 cells/ml. The work revealed that as the degree of immunosuppression increased, there was a sharp increase in cases of severe forms of the new coronavirus infection, as well as an increase in deaths. The average HIV RNA level was 578 161,9±103 457,4 copecks/ml. A high HIV viral load (more than 100 000 cop/ml) was observed in 41,5% of cases, and only in this group of patients were severe forms of the new coronavirus infection recorded and, as a consequence, death. All observed patients had comorbid pathology in the form of opportunistic infections and/or concomitant diseases. The most frequently recorded opportunistic infections were: candidiasis (77,9%), cerebral toxoplasmosis (17,8%), Pneumocystis pneumonia (16,1%), tuberculosis (14,4%), central nervous system damage caused by the Epstein-Barr virus (10,2%), cytomegalovirus infection (6,78%), HIV-associated anemia (3,39%), cervical cancer (1,69%). Often opportunistic infections had a polyetiological cause. Of the concomitant diseases, bacterial pneumonia (66,9%), chronic viral hepatitis (40,7%), cardiovascular diseases (26,3%), diseases of the gastrointestinal tract (21,2%), and nervous system were most often recorded (5,93%), urinary system (5,08%) and cancer (5,03%). In 89,8% of coinfected patients, prolonged release of SARS-CoV-2 was observed, which affected the duration of antiviral therapy and the length of hospitalization.Conclusion. The new coronavirus infection and HIV infection are the intersection of two epidemics with the subsequent mutually aggravating effect of pathogens on each other. Among the co-infected patients, young people of working age, reproductive age (30–49 years) with a long history of HIV infection (66,1%) and not taking ART (56,3%) predominated. The new coronavirus infection in HIV-infected patients more often occurred in a moderate form (75,4%), pneumonia was recorded in 83,1%. A severe form of the new coronavirus infection was recorded in 16,9% of patients. The work shows that as the degree of immunosuppression increased, there was a sharp increase in the frequency of severe forms of the new coronavirus infection. In the general cohort of patients, comorbid pathology was recorded in the form of opportunistic infections and/or concomitant diseases. Often opportunistic infections had a polyetiological cause. Multimorbidity aggravated the condition of patients and largely increased the risk of an unfavorable outcome. Mortality in the group of coinfected patients was 12,7%.