Abstract Background Infectious diseases (ID) education faces challenges with learner engagement, confidence, and specialty recruitment. Game-based learning, including educational escape rooms, offers an innovative strategy to increase engagement while reinforcing clinically relevant concepts. We designed an ID-themed escape room integrated into monthly clinical rotation curriculum for medical students and internal medicine residents. Methods General and targeted needs assessment informed eight learning objectives addressing board-relevant topics and common clinical errors: isolation precautions, zoonoses, empiric antimicrobial selection, laboratory safety, organism identification, molecular diagnostic interpretation, sexually transmitted infections, and MRSA-active antimicrobials. The physical outbreak-themed escape room used a hybrid puzzle structure with eight objective-aligned puzzles. Pilot testing by ID faculty, fellows, and medical students informed clarity, flow, and timing. Learners completed post-activity Likert-scale surveys assessing engagement, enjoyment, confidence, and perceived educational value. Results The escape room was implemented in April 2024. Twenty-five learners completed the post-activity survey. All participants agreed or strongly agreed that the activity was engaging, fun, enjoyable, and that they would like to participate in similar educational activities in the future. Most learners agreed or strongly agreed that the activity improved understanding, was a valuable addition to their learning experience, and increased confidence. Conclusions This ID-themed escape room provided an engaging, learner-centered approach to reinforcing clinical reasoning, antimicrobial decision-making, and infectious diseases concepts. Intentional alignment of learning objectives with puzzle design offers a reproducible roadmap for educators seeking to integrate escape rooms into clinical curricula. Future work should evaluate knowledge acquisition, scalability, sustainability, and effects on interest in ID careers.
Abstract Background The U.S. Centers for Disease Control and Prevention, through the National Healthcare Safety Network (NHSN), developed antimicrobial utilization (AU) metrics for hospital reporting and benchmarking. We applied this framework, using a modified NHSN definition of inpatient AU, to identify factors associated with antimicrobial use among solid organ transplant (SOT) recipients. Methods We conducted a retrospective single-center cohort study of first adult SOT recipients from 2010 to 2019. Inpatient AU during the first six months post-transplant was calculated as facility-wide days of therapy (DOT) per 1000 patient-days using a modified NHSN definition. Organ-specific multiple linear regression identified baseline characteristics associated with AU. Results Among 1845 recipients (293 heart, 531 kidney, 426 liver, 595 lung), AU varied by organ: heart 560, kidney 285, liver 622, lung 1111 DOT/1000 patient-days. In heart recipients, pretransplant infection requiring intravenous (IV) antibiotics and longer ischemic time were associated with higher AU, while transplant year, A-blood group, and medical condition at transplant predicted lower AU. In lung recipients, ischemic time increased AU, whereas age and lung allocation score decreased AU. In liver recipients, only the transplant year was associated with lower AU. In kidney recipients, ischemic time was associated with increased AU, while transplant year, functional status, and insurance type were associated with lower AU. Conclusion AU in the first six months post-SOT was substantial and varied by organ type, with specific baseline characteristics influencing its use. Applying AU metrics to SOT populations can inform targeted antimicrobial stewardship interventions.
Abstract Congenital cytomegalovirus (cCMV) infection is a leading cause of childhood deafness and disability worldwide. However, less is known about its epidemiology in low-income regions where most women are CMV-seropositive at conception. We found that cCMV is highly prevalent in rural Uganda (3.73%) and is associated with lower gravidity and placental malaria. We additionally report a high transmission intensity in the first years of life with 97.3% of children acquiring CMV IgG by age 3.
Abstract Background During evaluation for encephalitis, lumbar puncture (LP) plays a critical role in establishing a diagnosis. Repeat LP may be needed when the diagnosis remains in doubt, the specific etiology of encephalitis has not yet been identified, or to aid management decisions. However, findings on repeat LP have not been well characterized, potentially confounding interpretation. Here, we examine the clinical characteristics of patients with encephalitis who underwent repeat LP, the evolution of CSF parameters, and the indications for repeat LP during acute hospitalization. Methods This retrospective study analyzes LP and clinical data from 627 adults with all causes of encephalitis admitted between 2002 and 2022 across two hospital systems in Maryland and Texas. Results Of the 627 patients, 184 (29.3%) underwent repeat LP, with a median interval of 6 days between procedures, and more commonly among those with more severe presentations. Patients were more likely to undergo repeat LP in autoimmune than in infectious encephalitis (42/113 [37.2%] vs. 62/275 [22.5%], p=0.003). In infectious cases, CSF WBC counts decreased when repeat LP occurred ≥7 days after initial LP (p=0.016), whereas no decrease occurred in autoimmune cases. Repeat LP yielded a new diagnosis in 16/184 (8.6%). Among patients without initial pleocytosis, 51.4% developed pleocytosis on repeat LP, associated with worse outcomes. Diagnostic uncertainty was the most common indication. Conclusion Repeat lumbar punctures are performed in one-third of encephalitis hospitalizations and are more common in patients with autoimmune etiologies, severe disease, or diagnostic uncertainty. CSF dynamics differ between infectious and autoimmune etiologies.
Abstract Persistent high-risk HPV infections drive most anal cancers, disproportionately affecting people with HIV (PLH), for whom cytology-based screening remains essential. However, the biological context of abnormal anal cytology, particular regarding local immune cells, is incompletely understood. In this pilot study, 57 PLH underwent longitudinal non-invasive anal sampling over one year, including cytology, HPV genotyping, and phenotypic characterization of ano-mucosal immune cells. Anal HPV infection and persistence were highly prevalent. Abnormal cytology was associated with more concurrent (high-risk) HPV infections, lower viral loads, and anal immune-microenvironment characterized by increased CD4 and CD8 T cells with upregulated tissue residency, activation, and effector markers. In summary, non-invasive anal sampling revealed that abnormal anal cytology in PLH is characterized by a distinct microenvironmental signature marked by multiple (HR) HPV infections and increased levels of tissue resident, activated and effector ano-mucosal T cells, potentially highlighting the important role of local immune cells.
Abstract Background Candida spp. are often recovered from respiratory cultures and usually interpreted as colonization. Whether species identity adds prognostic information or identifies patients more likely to benefit from antifungal therapy remains uncertain. Methods We performed a single-center retrospective cohort study of hospitalized adults with respiratory Candida spp. from 2018 through 2023, excluding same-admission candidemia. Mortality was assessed through 30 and 90 days. Species and mortality associations were estimated with multivariable Cox models. Antifungal therapy was evaluated as a post-culture time-dependent exposure and in stabilized inverse-probability-weighted analyses. Results Among 548 patients (median age, 66 years; 54.9% male; 33.4% non-Hispanic Black; 33.6% Hispanic), 78.3% required mechanical ventilation, 72.3% received vasopressors, and 30-day mortality was 27.0%. C. albicans accounted for 478 isolates (87.2%), C. glabrata for 18 (3.3%), and other non-albicans Candida spp. for 52 (9.5%). Compared with C. albicans, C. glabrata was associated with higher 30-day mortality (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.05-4.56) and 90-day mortality (aHR, 2.18; 95% CI, 1.11-4.27). Antifungal therapy was not associated with lower 30-day mortality in time-dependent analysis (aHR, 1.25; 95% CI, 0.80-1.95) or weighted analysis (HR, 1.06; 95% CI, 0.64-1.75); 90-day analyses were also null. Conclusions Respiratory Candida spp. identified severe illness. C. glabrata identified a small high-mortality subgroup, but systemic antifungal therapy was not associated with improved survival, supporting caution against treating respiratory culture positivity alone.
Abstract Background Diphtheria, commonly resulting in severe respiratory or cutaneous disease, is caused by toxigenic strains of Corynebacterium diphtheriae; non-toxigenic strains can also cause disease. In the United States, only toxigenic disease is reportable, and the Centers for Disease Control and Prevention (CDC) perform the only Elek testing to confirm diphtheria toxin production. We examine the epidemiology, toxigenicity, and trends of C. diphtheriae isolates reported during 2016—2023 in the United States. Methods C. diphtheriae isolates submitted to CDC were cultured and tested by PCR and Elek. Laboratory and epidemiological data were linked; we conducted descriptive statistics by toxigenicity status. Results A total of 1155 C. diphtheriae isolates were submitted during 2016—2023; 96.1% (n=1110) were non-toxigenic, 3.0% (n=35) were non-toxigenic tox-bearing (NTTB), and 0.9% (n=10) were toxigenic. From 2016 to 2023, the annual number of reported isolates increased over 10-fold. Median patient age was 43 years (range: <1-98), and 68.6% (n=793) were male. Isolates were primarily obtained from cutaneous sites (69.8%, n=806). Risk factors for non-toxigenic and NTTB infections included housing instability and history of intravenous drug use. Nine of the 10 toxigenic isolates were from patients with recent international travel to a diphtheria-endemic country, and none were from patients with respiratory symptoms. Conclusions There has been an increase in C. diphtheriae isolates identified in the United States. However, toxigenic cases remained infrequent and risk factors appear to differ between patients with toxigenic compared with non-toxin producing infections. Risk factor awareness may help to guide public health intervention prior to confirmation of toxigenicity.
Abstract Infrequent standard-of-care (SOC) testing for respiratory syncytial virus (RSV) in adults with acute respiratory illness (ARI) contributes to underestimated disease burden. We compared RSV prevalence and RSV vaccine effectiveness (VE) among 14,044 adults ≥60 years with ARI ED/hospital admissions receiving SOC RSV testing versus those with SOC or salvaged respiratory specimen RSV testing. RSV was identified in 139 (0.99%) specimens by SOC testing alone versus 483 (3.44%) via SOC combined with salvage testing. Precision of VE against RSV-related ARI ED/hospital admissions improved substantially with inclusion of salvage testing compared to SOC testing alone (92% [67%- 98%] vs 90% [29%- 99%]).
Abstract High-dose corticosteroids may cause reactivation or relapse of hepatitis B virus infection. We investigated the virologic and clinical consequences of 6-8 weeks dexamethasone in hepatitis B virus infected/exposed/unexposed HIV-negative adults with tuberculous meningitis enrolled into a placebo-controlled trial. Dexamethasone was not associated with viral reactivation or increased liver injury.
Abstract Background Estimates of chlamydia and gonorrhea prevalence and incidence have typically focused on national-level epidemiology. Disaggregated estimates are useful for local public health decision making. Methods We developed a Bayesian hierarchical modeling framework to estimate the incidence and prevalence of chlamydia and gonorrhea for women in the United States. The model was calibrated to indicators from different data sources, including state and age-specific laboratory test positivity (data pooled over 2019–2023), and diagnosis rates (average of 2019-2023). At the national level, we calibrated to chlamydia prevalence and test coverage. We used the model to estimate state-level and national-level prevalence, incidence, and screening rates among women by state and age (15-24, 25-34, 35-44, 45-54, ≥55 years). Results For women aged 15–24 years, national-level chlamydia prevalence was estimated at 4.6% (95% uncertainty interval: 4.2-4.9%), gonorrhea prevalence was 0.4% (0.4–0.5%), and testing coverage was 33.4% (33.2–33.7.0%). Across states, corresponding chlamydia incidence estimates were 1.9-3.1 times as high as observed diagnosis rates; gonorrhea incidence estimates were 3.3-4.7 times as high as diagnosis rates. Chlamydia prevalence in women aged 15–24 years ranged 2.3%- 7.8% across states, and chlamydia incidence ranged 2.8%-12.4%. Gonorrhea prevalence ranged 0.09%-1%, and gonorrhea incidence ranged 0.5%-6.0%. Conclusions This study presents a new analytic framework for estimating incidence and prevalence at the state level. By integrating laboratory, diagnosis, and survey data, we provide more granular, actionable estimates of STI burden.
Abstract Background Staphylococcus aureus is a major human pathogen that can elicit immune-inflammatory responses and infections, largely driven by its broad repertoire of antigenic proteins. Understanding these factors is valuable for elucidating mechanisms of infection. Methods Fifty-two recombinant S. aureus antigen proteins were individually applied to cultured human dermal fibroblasts (HDFs). Following antigen stimulation of confluent HDFs (52 antigen + 44 controls; in three replicate plates), host protein responses were quantified using Olink inflammation, cardiovascular II, and III proteomic platforms. Data were analyzed using unsupervised clustering, differential expression analysis, and correlation network modeling to identify patterns of immune-inflammatory signals. Results Unsupervised analysis identified three distinct host-response clusters, with concordant separation observed across hierarchical clustering (Ward.D2) and t-SNE projection. These clusters can be broadly defined as a cytotoxic/inflammatory antigen cluster (Cluster_1), enriched for key virulence factors (e.g., HlgA, Atl.1, SasG.2) and characterized by marked upregulation of inflammatory mediators (including IL-6, IL-8, CXCL1, and CCL3). An immune modulation/surface protein cluster (Cluster_2), comprising adhesins and immune-evasion proteins (e.g., Chp, SSL11, Atl.2) associated with selective upregulation of AXIN1, IL-33, and DECR1. A small outlier antigen cluster (Cluster_4), consisting of LuKE and SdrD.1, which did not exhibit a clearly defined host-response profile. Differential expression analysis identified 12 core host proteins—including COL1A1, CXCL1, CXCL16, DLK-1, GLO1, IGFBP-1, IL33, IL6, IL8, MCP-1, TNF, and TRAIL-R2—with consistent and significant changes across clusters (FDR-adjusted p < 0.01). Conclusions This preliminary study suggests that S. aureus antigen proteins trigger a coordinated immune-inflammatory cascade in HDFs.
Abstract Background RSV transmission in tropical settings is often assumed to occur year-round, and preventive strategies are frequently recommended accordingly. However, sub-national variation in epidemic timing remains incompletely characterized. Granular local surveillance data may help refine timing of prevention, particularly in resource-limited settings prioritizing high-risk populations. Methods We analyzed aggregated RSV surveillance data from the Viral Respiratory Infection Surveillance Network (VIRAL Network LATAM–Colombia) across epidemiologic weeks 1–52 during 2022–2024. Data were obtained from 15 centers in seven climatically diverse cities spanning sea level to 2,640 m altitude. City-specific percentile thresholds were used to define transmission intensity. Epidemic patterns were categorized as concentrated, prolonged, or bimodal, and inter-city synchrony was assessed using pairwise Spearman correlations. Results Among 39,505 multiplex respiratory panels, 6,699 (17.0%) were RSV-positive. RSV was detected year-round in all cities, with off-season detections accounting for 16.2%–64.5% of annual cases. Five cities exhibited a synchronized epidemic corridor between March and July with high temporal concordance (all pairwise ρ ≥0.71, P < .01). Cartagena showed delayed coastal transmission, while Cúcuta demonstrated bimodal circulation with attenuated seasonality. Overall, two cities met criteria for concentrated transmission, four for prolonged transmission, and one for bimodal patterns. Conclusions Although RSV circulated throughout the year, epidemic activity converged temporally across most Colombian cities, with notable sub-national heterogeneity. These findings suggest that improved understanding of local epidemic timing could support geographically tailored implementation of RSV preventive strategies.
Background:A discrete choice experiment (DCE) subsequently incorporated into a multi-criteria decision analysis (MCDA) was used to compare clinicians' trade-offs between the benefits and risks of preemptive anti-cytomegalovirus (CMV) treatments posthematopoietic cell transplant (HCT). Methods:In the DCE, physicians completed forced-choice tasks comparing hypothetical treatments. We used logit models to estimate preference weights, relative attribute importance (RAI) score, and minimum acceptable benefit. The MCDA combined DCE-derived weighted attributes with clinical performance data to compare maribavir versus valganciclovir (using data from the AURORA study) and maribavir versus valganciclovir, ganciclovir, and foscarnet (using data from multiple sources). Analyses were conducted for 2 cohorts defined by baseline absolute neutrophil count (ANC) <1500/mm3 or ≥1500/mm3 at CMV reactivation. Results:In the DCE, all 7 attributes significantly impacted physician (n = 377) treatment choices; the most important were administration route/monitoring (RAI score = 25.7%), nephrotoxicity risk (RAI score = 18.5%), grade 3-4 neutropenia risk (RAI score = 18.1%), and week 8 viremia clearance (RAI score = 16.0%). Neutropenia at CMV reactivation significantly reduced physicians' preference for treatments with a higher grade 3-4 neutropenia risk. In the MCDA, overall benefit-risk scores were higher for maribavir than valganciclovir in both ANC cohorts. Among the considered attributes, the largest positive contributor to the overall benefit-risk score was viremia clearance at week 8, and the largest negative contributor was grade 3-4 neutropenia risk. Maribavir had a higher overall benefit-risk score than ganciclovir and foscarnet in both ANC cohorts. Conclusions:Within this MCDA framework, maribavir was preferred over valganciclovir, ganciclovir, and foscarnet for preemptive treatment of CMV after HCT.
Background:In high-burden, nonhuman immunodeficiency virus (HIV)-predominant settings, rapid exclusion of smear-negative pulmonary tuberculosis (TB) is as clinically critical as its confirmation. Delayed diagnosis prolongs empirical anti-TB therapy, defers treatment for alternative etiologies, and compounds socioeconomic burden. Bronchoalveolar lavage fluid (BALF) lipoarabinomannan (LAM) delivers point-of-care results immediately after bronchoscopy, yet its utility as a rule-out biomarker in non-HIV populations remains poorly characterized. Method:We conducted an exploratory prospective study at a tertiary referral center in Bangkok, Thailand (February 2023-February 2024). Adults with clinical and radiographic features of pulmonary TB, negative sputum acid-fast bacilli smear and molecular tests, and a clinical indication for bronchoscopy were enrolled. Bronchoalveolar lavage fluid was tested using the Alere Determine™ TB-LAM Ag lateral flow assay, compared with mycobacterial culture and polymerase chain reaction (Xpert MTB/RIF), supplemented by histopathology when applicable. Results:Of 219 participants (99.5% non-HIV; mean age 64 ± 13 years), 24 (11.0%) had confirmed TB. A negative BALF-LAM result carried a negative predictive value (NPV) of 92.2% (95% confidence interval [CI]: 87.1%-95.4%), reducing the posttest probability of TB from 11.0% to 8.4% (negative likelihood ratio: 0.74). Sensitivity was 45.8% (95% CI: 25.6%-67.2%) and specificity was 74.9% (95% CI: 68.2%-80.7%). No clinical or radiographic variable was independently associated with false-positive results. Under a composite reference standard, including clinical TB (n = 38), NPV remained 84.9% (95% CI: 78.5%-89.6%). Conclusions:Bronchoalveolar lavage fluid lipoarabinomannan functions as a reliable, rapid rule-out adjunct for smear-negative pulmonary TB in non-HIV-predominant, high-burden settings. Its high NPV, low cost, and point-of-care availability suggest potential utility within postbronchoscopy diagnostic algorithms, pending multicenter validation.
Background:Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (European Organization for Research and Treatment of Cancer [EORTC]/Mycoses Study Group Education and Research Consortium (MSGERC), Invasive Fungal Diseases in Adult Patients in ICU [FUNDICU]) classify treated cases and predict mortality is unclear. Methods:We retrospectively included adults in 48 French intensive care units who received systemic antifungal therapy for suspected IPA (January 2022 to July 2024). Patients were categorized as having modified EORTC/MSGERC probable IPA, FUNDICU probable IPA, or unclassified. Ninety-day mortality was analyzed using multivariable Cox regression; heterogeneity was explored with unsupervised clustering. Results:Among 371 treated patients, 217 (58%) met modified EORTC, 83 (22%) met FUNDICU, and 71 (19%) were unclassified. Overall, 90-day mortality was 62% and mortality did not differ by category (63%, 63%, 58%; log-rank P = .24). In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio [aHR] = 0.86, 95% CI .62-1.20; unclassified vs EORTC: aHR = 0.89, .62-1.30). Age (aHR 1.03/year, 1.02-1.05), Sequential Organ Failure Assessment (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified 6 phenotypes with 90-day mortality ranging from 40% to 80%. Conclusions:Nearly 1 in 5 intensive care patients treated for suspected IPA were not classifiable by EORTC/MSGERC or FUNDICU definitions. Mortality was more strongly associated with age, frailty, and acute severity than with classification category, supporting ICU-focused diagnostic frameworks and risk stratification; these associations should be read in light of the treatment-based design and do not establish that the definitions lack diagnostic value.
Background:Infectious complications and antimicrobial resistance (AMR) are leading causes of morbidity and non-relapse mortality (NRM) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The BATMO protocol, implemented in 2019, removed fluoroquinolone prophylaxis and introduced a personalized, stewardship-based antimicrobial approach. Methods:We retrospectively analyzed 323 allo-HSCT recipients transplanted between 2016 and 2023 at a single center, comparing outcomes in patients before (n = 115) and after (n = 208) BATMO implementation. Primary endpoints included overall survival (OS), NRM, incidence and microbiology of bloodstream infections (BSIs), antimicrobial resistance trends, and carbapenem use. Kaplan-Meier and cumulative incidence methods were employed. Results:Despite a significant increase in 30-day Gram-negative BSI incidence post-BATMO (24% vs 15%, P = .03), OS and NRM were similar between the two cohorts. Notably, the post-BATMO cohort included a substantially higher proportion of high-risk transplants, with a marked increase in haploidentical procedures and broader use of post-transplant cyclophosphamide. Interestingly, fluoroquinolone-resistant E. coli strains declined from 100% to 46% (P = .003), and overall Gram-negative resistance dropped from 75% to 36% (P = .006). Use of carbapenems remained unchanged (43% vs 53%, P = .1). Conclusions:The BATMO protocol demonstrates that withdrawal of fluoroquinolone prophylaxis and implementation of a targeted antimicrobial strategy can reduce resistance without compromising transplant outcomes. These findings support the long-term safety and efficacy of stewardship-based approaches in allo-HSCT.
Background:Human metapneumovirus (hMPV) is commonly associated with respiratory tract infections (RTIs) in young children. Method:We estimated the annual hospital incidence of hMPV RTIs in children under 5 years in Scotland from 2017 to 2023 using national hospital and laboratory data. Incidence outside Lothian, where testing practices were uncertain, was extrapolated from Lothian laboratory data, where hMPV testing was advised for all RTI admissions. We also examined the severity and mortality of laboratory-confirmed hMPV cases. We developed similar estimates for respiratory syncytial virus (RSV) and influenza A for comparison. Results:This analysis included 1462 laboratory-confirmed hMPV hospitalizations in children aged under 5 years. The extrapolated hMPV hospital incidence ranged from 19 per 100 000 to 537 per 100 000 in children aged under 5 years. The extrapolated incidence was 2 to 3 times higher than that based on laboratory-confirmed data. Hospital incidence was higher in infants than in toddlers. hMPV incidence dropped substantially during the 2020/21 season, followed by a rebound during the 2021/22 season. About 10% of hMPV RTI hospital admissions required hospital stay ≥5 days, but <1% required intensive care unit admissions or resulted in in-hospital death. RSV hospital incidence appeared substantially higher than the hMPV hospital incidence in this population. Conclusions:hMPV RTIs contribute to a substantial hospital burden in young children in Scotland. However, the RSV RTI burden is likely to be higher in the population unvaccinated against both viruses. Improved surveillance and diagnosis strategies are required to develop robust hospital burden estimates.
Toxoplasma gondii infection poses a significant risk for donor seropositive recipient seronegative heart transplant patients without prophylaxis. Guidelines remain unclear on the optimal duration of prophylaxis in this population. We present a case of disseminated toxoplasmosis presenting as a subacute diarrheal illness leading to fulminant infection with pulmonary involvement in a 38-year-old woman 6 months after stopping primary chemoprophylaxis.
Background:A recent proposal introduced criteria to distinguish uncomplicated from complicated candidemia and identify patients who might be candidates for a shortened (7-day) course of antifungal therapy. We evaluated the feasibility and potential impact of this strategy in a real-world cohort. Methods:This retrospective study included patients with candidemia at Lausanne University Hospital (2015-2024). We estimated the sample size required for a randomized non-inferiority trial comparing 7 vs 14 days of therapy for episodes with uncomplicated candidemia and the reduction in antifungal treatment days under a hypothetical 7-day treatment strategy. Results:Among 314 episodes of candidemia, 103 (33%) were classified as uncomplicated. Of the 264 (84%) episodes surviving beyond the first 5 days without limitation of care, 30-day mortality was lower in uncomplicated than complicated candidemia (7% vs 20%; P = .006). Based on a hypothetical randomized non-inferiority trial comparing 7 vs 14 days of antifungal therapy, assuming an expected event rate of 25% and a non-inferiority margin of 7.5%, 1103 patients would be required. Overall, the 314 episodes received 6377 days of antifungal therapy (median, 14 days; interquartile range 13-18). A shortened 7-day treatment strategy for uncomplicated candidemia would have reduced antifungal exposure by 799 treatment days, corresponding to a 13% reduction. Conclusions:Uncomplicated candidemia accounted for only one-third of episodes, and abbreviated therapy would yield a modest reduction in antifungal exposure. The large sample size required and limited stewardship benefit suggest that a randomized trial would be challenging to conduct.
