Pneumocystis jiroveci remains an important fungal pathogen in immunocompromised hosts. The environmental reservoir remains unknown. Pneumonia (PJP) results from airborne transmission, including in nosocomial clusters, or with reactivation after an inadequately treated infection. Pneumocystis pneumonia most often occurs within 6 months of organ transplantation, with intensified or prolonged immunosuppression, notably with corticosteroids and following cytomegalovirus (CMV) infections. Infection may be recognized during recovery from neutropenia and lymphopenia. Invasive procedures may be required for early diagnosis and therapy. Despite being a well-established entity, aspects of the pathogenesis of PJP remain poorly understood. The goal of this review is to summarize the data on the pathogenesis of PJP, review the strengths and weaknesses of the pertinent diagnostic modalities, and discuss areas for future research.

In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between 30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein–Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Galactomannan index (GMI) is established as a diagnostic tool for invasive aspergillosis (IA), while its utility in monitoring antifungal treatment (AFT) response and prognostic value remains unclear. This study evaluated the validity of serum GM as a biomarker for AFT monitoring and its prognostic significance by correlating GMI with clinical response and survival of IA. Patients with IA and at least two sequential serum GMI measurements were identified from the FungiScope registry. Joint models of event-time and longitudinal outcome were used for imputing missing GMI to account for the relationship between GMI and time to death, as well as GMI and time to drop-out for the survival analysis and AFT response analysis, respectively. Cox proportional hazards models and logistic regression models assessed survival and clinical response on GMI changes at day 7, with baseline log GMI as an adjustment covariate. Among 66 patients with IA, correlation between day 7 GMI predictions and observed values was 92% and 88% in the survival and AFT analysis, respectively. GMI decreased in both patients who died within 42 days and those who survived, but maintained higher in patients who died. GMI increased or declined less in patients who died within 42 days, whereas in survivors, a continuous decline of GMI was observed. Patients with a baseline GMI < 1 had a higher survival rate until day 42 (17/21, 81.0%) compared to those with GMI ≥ 1 (31/45, 68.9%), with a risk of death twice as high as with GMI < 1 (HR = 2.107, P = 0.19). Serum GMI is a non-invasive, predictive tool for estimating survival probability at onset of IA. Early GMI changes correlate with survival and could prompt timely AFT adjustment, potentially improving clinical outcomes. Additionally, GMI could serve as surrogate endpoint in clinical trials, facilitating development of new antifungal strategies.

The Mycoses Study Group Education and Research Consortium (MSGERC)—a group comprising clinicians, researchers, patients, and industry partners—meets every 2 years to review the most significant challenges facing the clinical mycology community and plan research, education, and advocacy strategies to prevent fungal infections and improve outcomes. Key themes of the 2024 biennial meeting included emergence of antifungal resistance, the effects of climate change on incidence of IFI, recent healthcare‐and community‐associated outbreaks and their management, and the potential benefits of novel approaches, such as innovative study designs, host‐directed diagnostics and therapies, and artificial intelligence in clinical and academic mycology.