Vikram, Holenarasipur R.

ABSTRACT Background Strongyloides stercoralis is an intestinal parasitic nematode that can infect humans with a 2%–7% prevalence in the United States. Immunosuppression is a crucial risk factor for disseminated infection. Diagnosis is often delayed and targeted treatment is frequently initiated late. We therefore sought to review the prevalence of positive Strongyloides antibody results and undertook a descriptive analysis of such patients. Methods We retrospectively reviewed patients with positive Strongyloides IgG serology from August 2012 to April 2023 across geographically distinct academic medical centers. Study period pre‐dated universal donor and recipient Strongyloides screening recommendation by the Organ Procurement and transplantation network (OPTN). Clinical presentation was classified into three categories: chronic infection (positive Strongyloides IgG serology without additional clinical manifestations), hyperinfection syndrome (positive serology with involvement of the skin, gastrointestinal tract, or lungs), and disseminated infection (positive serology with involvement beyond those typically involved in hyperinfection). Results A total of 412 patients were identified; median age was 59 years and 66% (272) were male. The primary indication for testing was pretransplant evaluation in 230 (56%), eosinophilia workup in 84 (20%), suspicion of symptomatic infection in 74 (18%), testing based on travel history in 27 (7%), and pre‐immunosuppression screening in 27 (7%). Furthermore, 401 patients (97.3%) were categorized as having chronic infection, 10 patients (2.42%) had hyperinfection, and one patient (0.24%) had disseminated infection, presenting with Escherichia coli bacteremia and meningitis. Symptomatic infection was more common at the Mayo Clinic in Rochester and Mayo Clinic Health Sciences than at the Arizona and Florida Mayo Clinic sites (6% vs. 2%, p = 0.079). Treatment was administered to 366/412 (89%) patients. Conclusion Most patients with positive Strongyloides serology were asymptomatic, and treatment regimens were not uniform. Patients who tested positive should be treated prior to immunosuppression initiation, though this was not systematically assessed in this cohort. The observed variability in treatment regimens highlights the need for standardized protocols.

Abstract Rationale Legionella species can cause severe community-acquired pneumonia requiring targeted antimicrobial therapy. The impact of time to effective Legionella-directed therapy on mortality is not well defined. Objectives To evaluate the association between time to effective Legionella-directed therapy and mortality in hospitalized patients with community-acquired Legionella pneumonia and to determine whether differences in treatment timing contribute to the excess mortality observed among immunocompromised patients. Methods A retrospective multicenter cohort study of adults hospitalized with laboratory-confirmed community-acquired Legionella pneumonia (2019–2025) was performed. Time from presentation to effective therapy (macrolide, fluoroquinolone, or doxycycline) was recorded. The primary outcome was 90-day mortality. Multivariable logistic regression analysis was performed, adjusting for age, SOFA-2 score (first 6 hours), and immunocompromised status. Secondary analyses included a 24-hour landmark Cox model for 90-day survival and multivariable logistic regression for 30-day mortality. Results Among 310 patients (median age 66.9 years, 44.8% immunocompromised), 90-day mortality was 17.4%. Every 6-hour delay in effective therapy was independently associated with increased 90-day mortality (adjusted OR per 6 hours: 1.11; 95% CI, 1.06–1.17; P < 0.001). Delays >24 hours were associated with worse 90-day survival (adjusted HR, 2.72; 95% CI, 1.65–4.77; P < 0.001). Time to effective therapy was also independently associated with increased odds of 30 day mortality (adjusted OR per 6 hours: 1.06; 95% CI: 1.01-1.11, p = 0.024). Immunocompromised patients experienced longer delays (median, 7.1 versus 3.3 hours; P < 0.001) and higher unadjusted 90-day mortality (22.3% versus 13.5%; P = 0.041), but immunocompromised status was not independently associated with mortality after adjusting for severity and treatment timing. Conclusion Longer time to effective Legionella-directed therapy was independently associated with increased mortality in a graded fashion. Delays were more common among immunocompromised patients, partially accounting for excess mortality in this group, suggesting that timely pathogen-directed therapy may represent a clinically important and potentially modifiable contributor to risk.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PCP) can cause severe hypoxemic respiratory failure in immunocompromised patients. Contemporary outcomes of venovenous extracorporeal membrane oxygenation (VV ECMO) support for PCP are poorly characterized, and existing reports are limited to small case series. DESIGN: Retrospective cohort study. SETTING: International registry study using the Extracorporeal Life Support Organization (ELSO) registry. PATIENTS/SUBJECTS: Adults with PCP-associated hypoxemic respiratory failure supported with VV ECMO between 2011 and 2024. INTERVENTIONS: VV ECMO. MEASUREMENTS AND MAIN RESULTS: A total of 209 patients with PCP-associated respiratory failure supported with VV ECMO were identified. The overall in-hospital mortality was 60.8%. Survivors were younger than nonsurvivors (median age 41.9 vs. 46.8 yr; p = 0.047). Duration of mechanical ventilation before VV ECMO was longer among nonsurvivors (median 4.7 vs. 1.6 d; p = 0.019). The proportion of patients with HIV infection was similar among survivors and nonsurvivors (19.5% vs. 22.1%; p = 0.73). Pre-ECMO vasopressor use, prone positioning, and renal replacement therapy were common and did not differ between groups. Clinical course was characterized by prolonged VV ECMO support (median 18.6 d) and frequent complications, including pneumothorax (21.1%), renal replacement therapy during VV ECMO (31.6%), intracranial hemorrhage or stroke (7.7%), and major pulmonary or gastrointestinal hemorrhage (16.8%). PCP accounted for a small proportion of VV ECMO runs reported to the ELSO registry throughout the study period at 0.36% of reported cases. No significant temporal trend in mortality was observed. CONCLUSIONS: PCP-associated respiratory failure supported with VV ECMO is associated with substantial mortality and prolonged VV ECMO support. These findings provide contemporary benchmarks that may inform VV ECMO candidacy discussions and expectations in this challenging patient population.

ABSTRACT Background Intravesical Bacillus Calmette–Guerin (BCG) is a live attenuated vaccine for tuberculosis. Intravesical BCG (iBCG) administration is a highly effective immunotherapy for non‐muscle invasive bladder cancer (NMIBC). Although live attenuated vaccines are generally contraindicated in solid organ transplant recipients (SOTR), iBCG has been utilized for NMIBC in SOTR. We describe the clinical manifestations, management, and outcomes of disseminated Mycobacterium bovis ‐BCG infection (Mb‐BCGi) following iBCG therapy in SOTR for NMIBC. Methods All adult patients (> 18 years of age) diagnosed with NMIBC who received iBCG across three tertiary referral and transplant centers between 2000 and 2025 were identified. The study cohort consisted of SOTR who had received iBCG for NMIBC and subsequently developed disseminated Mb‐BCGi. English language literature review was performed to identify additional cases. Results A total of 4207 patients received iBCG during the study period. Thirty (0.71%) were SOTR, of whom two (6.7%) developed disseminated Mb‐BCGi, including bloodstream infection and prostate abscesses. Literature review identified two additional disseminated Mb‐BCGi cases in SOTR with lungs, bloodstream, and native kidney involvement, and one fatality. All cases required extended antimycobacterial therapy. Median times from SOT to Mb‐BCGi and from iBCG to Mb‐BCGi were 104 and 8 months, respectively. Conclusion SOTR appear to be at a higher risk of disseminated Mb‐BCGi following iBCG. Administration of iBCG in SOTR with NMIBC warrants careful risk‐benefit assessment and subsequent close monitoring. image

In a large, multicenter cohort of HIV and non–HIV immunocompromised patients with Pneumocystis jirovecii pneumonia, chest CT most commonly demonstrated diffusely distributed ground-glass opacity, with no imaging features distinguishing between immunocompromise etiology.

Abstract Objective: To define the incidence of donor-derived infection (DDI) in recipients of solid organ transplant (SOT) from donors with positive blood cultures and to assess the impact of shorter versus longer duration of targeted preemptive antibiotic therapy (PAT). Design: Retrospective, single-center, cohort study. Setting: Mayo Clinic Arizona. Patients: Recipients transplanted between 1/1/2019 and 7/1/2024 who received an organ from a donor with positive blood cultures. Methods: The primary outcome was incidence of DDI. Secondary outcomes included duration of PAT and incidence of donor blood culture contamination. Results: Among 199 SOT recipients from 167 unique donors with positive blood cultures, two recipients developed confirmed DDI within 30 days of SOT. Both cases were gram negative bacillary bacteremia not treated in donors and occurred immediately posttransplant prior to adequate recipient PAT. Six-month graft survival and recipient survival were 96.5% and 97.5% respectively. 139 recipients (69.8%) received PAT for a median duration of 7 days. There was no difference in rate of infections between recipients provided with ≤7 days versus 8–14 days of PAT for donor blood cultures; however, recipients who received 8–14 days had more Clostridioides difficile infections (CDIs) within 60 days of SOT (7.7% vs 1.5% ≤ 7 days, P = .040) and were more often discharged on intravenous antibiotics (32.3% vs 11.3%, P < .001). Conclusion: We observed a low rate of DDI following receipt of organs from donors with positive blood cultures. DDI occurred in cases without adequate donor/recipient treatment. Longer durations of targeted PAT resulted in more CDI and intravenous antibiotics on discharge.

This article describes the typical and atypical chest imaging appearances of Pneumocystis jirovecii pneumonia.

Abstract Background Legionella pneumonia is an important cause of severe pneumonia, yet contemporary data describing its clinical phenotype, diagnostic patterns, and outcomes in the modern era are limited. Methods We conducted a retrospective multicenter cohort study of adults with laboratory-confirmed Legionella pneumonia across an integrated health system between January 2019 and September 2025. The primary outcome was 30-day mortality. Severe disease was defined as having a requirement for high-flow nasal cannula, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Univariate and multivariable logistic regression were used to identify predictors of mortality and severe disease. Results There were 344 patients with laboratory-confirmed Legionella pneumonia during the study period. The median age was 66.6 years, and 45.1% were immunocompromised. Most patients required hospital admission (94.2%), with 36.1% admitted to the intensive care unit; 22.7% required mechanical ventilation and 1.5% ECMO. Thirty- and 90-day mortality were 11.9% and 16.6%, respectively. In multivariable analysis, cirrhosis (OR 10.2, 95% CI 2.15–48.3, P = .003), immunocompromised status (odds ratio [OR] 2.24, 95% CI 1.05–4.77, P = .036), age (OR 1.03, 95% CI 1.00–1.06, P = .031), and lymphopenia at presentation (OR 2.09, 95% CI 1.02–4.24, P = .043) were independently associated with increased 30-day mortality. Among patients who were polymerase chain reaction (PCR) or culture positive, urinary antigen testing was positive in only 25.6%. Conclusions Legionella pneumonia was associated with substantial short-term mortality. Cirrhosis, age, immunocompromised status, and lymphopenia at presentation emerged as independent predictors of 30-day mortality, underscoring the importance of host vulnerability in determining outcomes.

ABSTRACT Background Solid organ transplant (SOT) recipients are at risk for Pneumocystis jirovecii pneumonia (PCP), yet how their clinical phenotype and outcomes compare with other immunocompromised patients without HIV remains poorly defined. Methods We conducted a multicenter retrospective cohort study of adults with proven or probable PCP from 2017 to 2025, including 95 SOT recipients and 588 non‐SOT, non‐HIV immunocompromised patients. The primary outcome was 90‐day mortality, secondary outcomes included new renal failure requiring dialysis, and 30‐day mortality. Outcomes were analyzed using inverse probability weighting (IPW) with winsorization to adjust for baseline differences. Results In unadjusted analysis, SOT recipients had lower 90‐day mortality (hazard ratio [HR]: 0.62, 95% CI 0.39–0.97, p = 0.037). After IPW with winsorization of extreme weights, SOT status remained associated with lower 90‐day mortality (HR: 0.32, 95% CI 0.13–0.76, p = 0.009), and 30‐day mortality (HR: 0.35, 95% CI: 0.14–0.92, p = 0.034). SOT recipients had higher odds of renal failure requiring dialysis in unadjusted analysis (OR: 3.49, 95% CI 1.94–6.14, p < 0.001), which persisted after IPW adjustment (OR: 1.62, 95% CI: 1.04–2.51, p = 0.032). Conclusions Despite higher rates of renal failure requiring dialysis, SOT recipients with PCP experienced significantly improved short‐ and intermediate‐term survival compared with other non‐HIV immunocompromised patients, underscoring the need for further investigation into transplant‐associated contributors to PCP outcomes.