Search Results (98)

Introduction: This study aimed to assess the accuracy of real-time polymerase chain reaction (PCR) as a diagnostic tool for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients and evaluate the applicability of quantification cycle (Cq) data for PCP diagnosis. Methods: Clinical and laboratory data were collected from medical records of 96 immunocompromised patients hospitalized at the Hadassah hospital from 2018 to 2022, for lower respiratory tract infection. PCP diagnosis was independently categorized by two infectious disease specialists, blinded to PCR results, as either “definite” (confirmed by microscopic identification of P. jirovecii) or “probable” (compatible clinical data and negative microscopy). Clinical characteristics, PCR test performance, and Cq values were then compared between these PCP diagnostic groups and a control group of 85 patients who underwent bronchoscopy for indications unrelated to P. jirovecii infection. Results: The PCR test was found to be highly reliable for diagnosing PCP, with high sensitivity and specificity (93.1%, 98.7%, respectively), a positive predictive value (PPV) of 96.4%, a negative predictive value (NPV) of 97.1%, a negative likelihood ratio of 0.71, and a positive likelihood ratio of 46.5. A Cq cutoff value of 21.89 was found to discriminate between probable PCP and definite PCP. In addition, patients with probable PCP had lower in-hospital mortality than those with definite PCP or no PCP. Conclusions: PCR offers a promising approach for diagnosing PCP in immunocompromised patients with negative respiratory microscopy results. While further research may be warranted, its use may allow for more timely treatment and potentially improved outcomes. Full article

Background: Pneumocystis jirovecii pneumonia (PJP) remains a serious threat to non-HIV immunocompromised patients, who often experience rapid disease progression, delayed diagnosis, and higher mortality. Standard treatment with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) is based primarily on data from HIV-positive populations, despite differences in immune response and drug tolerability. Objective: This narrative review critically synthesizes the available evidence on lower-dose TMP-SMX strategies for PJP in non-HIV patients and explores the potential role of individualized dosing approaches to improve outcomes. Findings: Emerging retrospective data suggest that lower-dose regimens (<15 mg/kg/day) may provide similar survival outcomes with fewer adverse effects. The intense inflammatory response observed after treatment initiation in non-HIV patients, potentially exacerbated by high-dose therapy, may contribute to clinical deterioration. This raises the possibility that TMP-SMX dosing itself could influence immune-mediated lung injury. While adjunctive corticosteroids are frequently used to temper inflammation, their benefit remains uncertain. Conclusions: Existing data suggest that lower-dose TMP-SMX may be effective and better tolerated in some non-HIV patients with PJP. A personalized approach to dosing, informed by clinical and host-specific factors, represents a promising strategy to optimize outcomes and minimize harm. Future research should prioritize precision medicine frameworks and prospective evaluation of individualized dosing protocols. Full article

Background: Pneumocystis jirovecii primarily causes pneumonia in immunosuppressed individuals, particularly those living with advanced HIV/AIDS. Extrapulmonary dissemination is uncommon, with bone marrow involvement described in only a handful of cases globally. Bone marrow infection occurs in the setting of severe immunosuppression, poses diagnostic challenges, and carries a high mortality rate. Methods: We describe the case of a 34-year-old man newly diagnosed with HIV/AIDS, presenting with severe immunosuppression and Pneumocystis jirovecii pneumonia. The patient initially improved with cotrimoxazole and corticosteroids, but was readmitted shortly after discharge with abdominal pain, diarrhea, and worsening pancytopenia. A bone marrow biopsy revealed Pneumocystis jirovecii cysts, confirming disseminated infection. Concomitant Kaposi sarcoma involving the skin and gastrointestinal tract was also diagnosed. Despite antimicrobial therapy, the patient’s condition worsened, leading to multisystem organ failure and death two months later. Conclusions: This case highlights a rare presentation of disseminated Pneumocystis jirovecii infection with bone marrow involvement in a patient with advanced HIV/AIDS. Although infrequent, this complication should be considered in individuals with Pneumocystis jirovecii pneumonia who develop persistent cytopenias and systemic symptoms. Diagnosis depends on histopathologic confirmation, which may lead to under-recognition. Early suspicion and individualized management are essential, though the optimal treatment approach for extrapulmonary infection remains undefined. Full article

Pneumocystis jirovecii is an opportunistic fungus that causes severe pneumonia in immunosuppressed individuals. While Pneumocystis colonization, a subclinical form of infection, has been studied in different populations, its implications during pregnancy remain poorly understood. Given the immune modulation of pregnancy, maternal colonization or infection may contribute to vertical transmission and neonatal respiratory complications. This scoping review aims to map the existing evidence on Pneumocystis colonization/infection during pregnancy, identifying knowledge gaps, prevalence, risk factors, and potential neonatal outcomes. A systematic literature search was conducted in three databases following PRISMA-ScR guidelines. A total of 26 studies were included, covering Pneumocystis pneumonia cases (n = 19) and Pneumocystis colonization (n = 7). The review found that most Pneumocystis pneumonia cases in pregnant women were associated with HIV before antiretroviral therapy. More recent cases were related to hematologic malignancies. Pneumocystis colonization rates varied widely (5.4–46.5%). Evidence of vertical transmission was observed, but neonatal impact remains underexplored. This review highlights the need for HIV screening in pregnant women and the need to include Pneumocystis in the diagnosis of pregnant women with pneumonia. Increased awareness and research on Pneumocystis in pregnancy are necessary to improve maternal and neonatal outcomes. Future studies should focus on vertical transmission and neonatal respiratory health. Full article

Background/Objectives: This study examines the clinical characteristics of Pneumocystis jirovecii pneumonia (PjP) in non-Human immunodeficiency virus (HIV) patients in Hungary to describe its local epidemiological properties. Methods: Our study was conducted at a clinical center with more than 1700 beds at the University of Debrecen in Hungary. We included all patients without HIV infection for whom a diagnostic evaluation for Pneumocystis infection had been requested between 1 January 2022 and 31 December 2024. Results: In total, 21 cases of PjP were identified from 122 requests at the University of Debrecen Clinical Center between 2022 and 2024. The overall 30-day mortality rate was 43% in PjP. Admission to the intensive care unit (odds ratio [OR] 5.44, 95% confidence interval [CI] 1.87–14.09, p = 0.001), the need for mechanical ventilation (OR 4.09, 95% CI 1.45–12.14, p = 0.015) and hematological malignancies (OR 3.24, 95% CI 1.23–9.18, p = 0.024), were associated with Pneumocystis PCR positivity. Furthermore, a significant association was observed between elevated levels of C-reactive protein (OR 1.01, 95% CI 1–1.01, p = 0.001), 30-day mortality (OR 2.86, 95% CI 1.09–7.92, p = 0.049), and Pneumocystis PCR positivity. Regarding diagnostic platforms used, Fujifilm Wako assay detected serum (1-3)-β-D-glucan positivity (>7 pg/mL) from 352 copies/mL in non-HIV patients with probable PJP. Conclusions: Our study serves as a gap-filling investigation, providing an overview of Pneumocystis epidemiology in the Central European region. Full article

A commercially available loop-mediated isothermal amplification assay (LAMP) for the detection of Pneumocystis jirovecii (P. jirovecii) has been evaluated for the diagnosis of Pneumocystis pneumonia (PcP) in critically ill patients. Altogether, 109 lower respiratory tract specimens from 95 patients with a positive P. jirovecii test in routine diagnostics were collected from five distinct university hospitals in Germany. All samples were tested with a qPCR and eazyplex^® LAMP assay. qPCR was set as the gold standard and was evaluated beforehand with samples from 100 patients categorized to have proven, probable, and possible PcP according to the EORTC/MSGERC guidelines. The sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the LAMP were assessed. Sensitivity was 68%, specificity was 86%, and PPV and NPV were 99% and 16%, respectively. All patients with proven PcP were positive in the LAMP. There was a weak correlation between the time to positivity and the fungal load (squared Pearson correlation coefficient (r²) = 0.5653). A positive result in the LAMP indicates a PcP. Because of the low sensitivity, negative results do not rule out an infection and should be clarified with further molecular methods. The LAMP should be used in patients in whom a PcP is expected, not for screening only. Full article

Background and Objectives: Secondary pulmonary fungal infections in coronavirus disease 2019 (COVID-19) remain underexplored despite emerging reports linking them to heightened morbidity. Comorbidities, steroid use, and prolonged hospital stays can predispose patients to opportunistic fungi. This study aimed to evaluate the impact of fungal coinfection on inflammatory markers, disease severity, antifungal resistance profiles, and outcomes in hospitalized COVID-19 patients. Methods: This retrospective observational study enrolled 280 adults (≥18 years) with real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to a tertiary care center (January 2023–December 2024). Patients were divided into a COVID-19-only group (n = 216) and a COVID–fungal group (n = 64) based on bronchoalveolar lavage, sputum, and/or blood culture positivity for fungal pathogens. Inflammatory markers (C-reactive protein (CRP), procalcitonin, the neutrophil-to-lymphocyte ratio, and the systemic immune inflammation index) and severity scores (Acute Physiology and Chronic Health Evaluation II, CURB-65 score, and the National Early Warning Score) were measured. We assessed antifungal susceptibilities and recorded ICU admissions, ventilation, hospital length of stay, and mortality. Results: Aspergillus fumigatus (31.3%), Candida albicans (28.1%), Cryptococcus neoformans (7.8%), Pneumocystis jirovecii (6.3%), and Mucorales (6.3%) dominated; Candida glabrata, Candida tropicalis, and mixed infections were also noted. Multidrug-resistant (MDR) isolates or resistance to triazoles occurred in 25.0% of cultures. The COVID-19–fungal group showed significantly higher CRP (85.7 vs. 71.6 mg/L, p < 0.001), procalcitonin (2.4 vs. 1.3 ng/mL, p < 0.001), and APACHE II scores (18.6 vs. 14.8, p < 0.001). intensive-care unit admissions (39.1% vs. 19.9%, p = 0.004) and mechanical ventilation (26.6% vs. 10.2%, p = 0.01) were more frequent with fungal coinfection. Mortality trended at a higher rate (15.6% vs. 7.4%, p = 0.06). Conclusions: Pulmonary fungal coinfections intensify the inflammatory milieu, elevate severity scores, and lead to more frequent ICU-level interventions in COVID-19 patients. Early identification, guided by culture-based and molecular diagnostics, alongside prompt antifungal therapy, could mitigate adverse outcomes. These findings underscore the critical need for proactive fungal surveillance and rigorous stewardship in managing severe COVID-19 pneumonia. Full article

Background/Objectives: Pneumocystis jirovecii pneumonia (PJP) is the most frequently diagnosed AIDS-defining illness in Europe, with especially high mortality in HIV-negative patients caused by delayed diagnosis and low awareness. This study aims to evaluate cytokine release assays (CRA) to facilitate a less invasive and resource-efficient PJP specific diagnostic test. We focus on the P. jirovecii antigens Kexin 1 (KEX1), MSG1, and MSG2, which were identified in prior studies as immunologically relevant. Methods: Whole blood samples from 50 participants—22 healthy individuals and 28 immunocompromised individuals, including 8 with proven PJP—were stimulated in vitro with full-length and partial KEX1, MSG1, MSG2, and a combination of all three antigens (PJ-MIX). Following 24 h incubation at 37 °C, cytokine levels of IL-2, IFN-γ, IL-17A, and IL-17F were measured. Results: Stimulation with full-length KEX1, MSG1, MSG2, and PJ-MIX antigens induced higher IL-2 concentrations in the healthy control group compared to the groups IL-2 baseline levels and to the group of proven PJP cases. Similarly, stimulation with full-length KEX1, MSG1, and PJ-MIX elevated IFN-γ levels in the healthy control group compared to baseline IFN-γ levels. Conclusions: Our findings highlight the potential of IL-2 and IFN-γ release following stimulation with PJ antigens, with PJ-MIX eliciting the strongest and most significant responses, suggesting a cumulative antigen effect. This pilot study establishes a foundation for a PJP-specific CRA, deepening our knowledge of T-cell immunity against PJP. Clinically, such a test could, among other applications, evaluate at-risk patients who should receive prophylaxis and may consequently reduce PJP-related morbidity and mortality. Full article

Background: HIV-related opportunistic infections like Pneumocystis jirovecii Pneumonia (PCP) remain a major contributor to child morbidity and mortality globally. PCP accounts for over 60% of AIDS in the first year of life and is responsible for a third of AIDS in children globally. Cotrimoxazole prophylaxis, which is an intervention directed towards tackling this burden, has not attained remarkable coverage despite advocacy towards scale-up. This work was therefore aimed at evaluating the efficacy of cotrimoxazole in the prevention of PCP among children exposed to and infected with HIV by carrying out a systematic review. Methods: Key scientific databases were searched for primary studies not older than 15 years old without language restrictions. Randomized Control Trials (RCTs) and Cohorts comparing the effectiveness of cotrimoxazole versus placebo in the prevention of PCP among children (<17 years) exposed to and infected with HIV were selected. Studies with a duration of follow-up not less than 3 months long were included. A meta-analysis was conducted on RevMan 5.3 statistical application software following data extraction, and the data quality and risk of bias were also assessed. Exactly Ten (10) studies were selected and analyzed. Findings: It was observed that cotrimoxazole had beneficial effects in terms of a reduction in mortality among HIV-exposed and infected children, as 72 fewer children in 1000 (based on an absolute 95% CI) will die as a result of cotrimoxazole compared to a placebo. Cotrimoxazole also significantly reduces hospital admissions (p-value of 0.008). The adverse events associated with cotrimoxazole are comparable to a placebo when co-administered with ARTS (p = 0.90), which did not impact adherence. Conclusion: The benefits of cotrimoxazole prophylaxis far outweigh its risks. Therefore, scaling up the intervention is recommended as a prophylactic for wider coverage, especially in resource-limited settings. Full article

Background/Objectives: Pneumocystis jirovecii pneumonia is a significant contributor to morbidity and mortality in patients with solid organ transplants. Sulfamethoxazole–trimethoprim prophylaxis has greatly reduced the incidence of this deadly fungal infection. Traditional prophylactic dosing includes single strength (400–80 mg) daily or double strength (800–160 mg) thrice weekly, but is limited by side effects. This study evaluates the efficacy and tolerability of a sulfamethoxazole–trimethoprim single-strength thrice-weekly prophylactic dosing strategy. Methods: This was a single-center, retrospective chart review of 421 patients with 423 total heart transplants at Cedars Sinai Medical Center between July 2016 and June 2020.A total of 361 patients (363 heart transplants) were started on single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year, based on institutional guidelines. Results: Patients were followed for a median of 3.86 years (range 0.17 to 6.57). Sulfamethoxazole–trimethoprim was started at a median of 7 days (range 0 to 132) for median duration of 11.5 months (range 0.25 to 22). There were no documented Pneumocystis jirovecii pneumonia cases during the study period. At 1 year, 36% of patients had discontinued sulfamethoxazole–trimethoprim. The most common causes for discontinuation were leucopenia (30.8%) and hyperkalemia (2.2%). Conclusions: In our experience, single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year effectively prevents Pneumocystis jirovecii pneumonia after heart transplant. Further multicenter studies with other patient populations will need to be performed to explore this well-tolerated strategy. Full article

Pneumonia caused by Pneumocystis jirovecii infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia. Here, we employed 16S rRNA metataxonomic sequencing to profile the respiratory microbiota of patients with mild-moderate and severe PCP. Our results show that the upper and lower airways of PCP patients have bacterial profiles which have been associated with a pro-inflammatory response. Furthermore, we find that severe PCP is associated with lower bacterial diversity and an increase in Prevotella and a decrease in Neisseria. Functionally, severe PCP was associated with a decrease in metabolic pathways of molecules with anti-inflammatory and antimicrobial properties. To our knowledge, this is the first study showing an association of PCP severity with shifts in the respiratory microbiome and may provide some insight into which patients are more susceptible to the more severe manifestations of the disease. Full article

Background: We report a case of an adult patient with newly diagnosed human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), and acute respiratory distress syndrome (ARDS) secondary to pneumocystis and cytomegalovirus pneumonia that were present on presentation, which were successfully managed with venovenous extracorporeal membrane oxygenation (VV-ECMO). Case Presentation: A 40-year-old patient with a past medical history of asthma was admitted to a local hospital due to dyspnea, cough, and wheezing, where the patient was diagnosed with HIV infection, ARDS, and combined pneumocystis and cytomegalovirus pneumonia. Their pulmonary function quickly declined, necessitating mechanical ventilation (MV). After all conventional therapies failed, the patient was transferred to a tertiary medical center for VV-ECMO therapy. The patient was successfully treated with antiretroviral therapy (ART), antibiotics, antivirals, steroids, and 48 days of VV-ECMO support, with complete resolution of their respiratory symptoms. The patient was discharged on hospital day 82. Conclusions: HIV-positive patients with ARDS that is complicated by opportunistic pulmonary infections can be successfully managed with ART, appropriate anti-infective therapies, and VV-ECMO. Full article

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. Full article

Infectious diseases caused by fungal sources are of great interest owing to their increasing prevalence. Invasive fungal infections, including invasive pulmonary aspergillosis caused by Aspergillus fumigatus, and Pneumocystis pneumonia caused by Pneumocystis jirovecii, are significant causes of morbidity and mortality among immunocompromised patients. The accurate and timely detection of these pathogens in this high-risk population is crucial for effective patient management. We developed a multiplex real-time polymerase chain reaction (PCR) assay, RF2 mRT-PCR, specifically designed to detect two respiratory fungi, P. jirovecii and A. fumigatus, and evaluated its performance in specimens of patients with lower respiratory tract infection. The performance was evaluated using 731 clinical samples, 55 reference species, and one synthetic DNA. The reproducibility test yielded a probit curve with a lower limit of detection of 19.82 copies/reaction for P. jirovecii and 64.20 copies/reaction for A. fumigatus. The RF2 mRT-PCR assay did not cross-react with non-A. fumigatus Aspergillus species or other common bacterial and viral species, and showed 100% in vitro sensitivity and specificity with reference assays. Additionally, it simultaneously detected A. fumigatus and P. jirovecii in co-infected samples. Therefore, the RF2 mRT-PCR assay is an efficient and reliable tool for in vitro diagnosis of A. fumigatus and P. jirovecii pulmonary infections. Full article

A 2.5-month-old girl admitted for failure to thrive and severe pancytopenia was diagnosed with methylmalonic acidemia (MMA) secondary to transcobalamin II deficiency, an inborn error of vitamin B12 metabolism. Opportunistic Cytomegalovirus and Pneumocystis jirovecii pneumonia led to severe acute respiratory distress syndrome (ARDS) and immune reconstitution inflammatory syndrome (IRIS) after treatment initiation with vitamin B12 supplementation. In children with interstitial pneumonia-related ARDS, normal lymphocyte count should not delay invasive procedures required to document opportunistic infections. MMA can be associated with underlying lymphocyte dysfunction and vitamin B12 supplementation can fully reverse the associated immunodeficiency. IRIS may appear in highly treatment-responsive forms of pancytopenia in children and prompt treatment of dysregulated inflammation with high-dose corticosteroids should be initiated. Full article