BACKGROUND:Previous studies examining Histoplasma antigen trends are largely in people living with HIV (PLWH) before the antiretroviral therapy era, with limited generalizability to modern cohorts of histoplasmosis. METHODS:We conducted a single-center, retrospective study of adult patients diagnosed with histoplasmosis by positive antigen testing and undergoing treatment between 2007 to 2021. Mean rates of antigen clearance were estimated using a linear mixed effects model. Time to H. capsulatum antigen negativity was calculated using competing risk analysis. Per-patient, mean antigen levels were compared at time of diagnosis and subsequent 6mo intervals. RESULTS:83 patients met inclusion criteria: 25 transplant, 21 immunocompetent, 16 biologic therapy, 11 PLWH, and 10 with other immunocompromise (OI). The transplant (-0.07), biologic (-0.07), and OI groups (-0.05) cleared antigenuria significantly slower than PLWH (-0.21) and the immunocompetent group (-0.16). Median time to antigen negativity in the presence of competing risk of death was transplant: 20.3 months (95% CI: 11.6, 69.3), biologic: 14.6 months (9.0, 42.6), OI: 13.2 months (2.0, 82.5), PLWH: 12.9 months (1.9, 19.2), and immunocompetent: 6.8 months (2.8, 13.0). At one year, antigen positivity was more common in immunocompromised than immunocompetent patients (22/40, 55% vs. 3/16, 19%; p = 0.02) and among the immunocompromised groups only transplant, biologic, and OI patients had positivity at two years. CONCLUSIONS:Patients with chronic non-HIV immunosuppression demonstrated persistent antigenuria and cleared antigen more slowly compared to immunocompetent patients and immune reconstituted PLWH. Given the association of antigen persistence with immune status, its clinical significance in non-HIV immunocompromised populations requires evaluation.
BACKGROUND:Vancomycin is frequently administered empirically for suspected serious bacterial infections (SBI) in the pediatric intensive care unit (PICU) despite low prevalence of methicillin-resistant Staphylococcus aureus (MRSA). METHODS:We performed a multicenter interrupted time series (ITS) study including five PICUs in three U.S. children's hospitals evaluating the impact of a multifaceted stewardship intervention including consensus guidelines, education, and group level audit and feedback on reducing empiric vancomycin use. The primary outcomes were (1) vancomycin administration within 12 hours of suspected SBI onset and (2) empiric vancomycin days of therapy (DOT) during the first 3 days after suspected SBI onset. Secondary outcomes included overall vancomycin DOT/1000 patient days; organ dysfunction at days 3 and 7; 14-day mortality; and invasive MRSA infection not covered empirically. Empiric vancomycin use was modeled using mixed-effects logistic regression and vancomycin DOT was modeled using mixed effects Poisson regression. RESULTS:Among 4,549 episodes targeted by the intervention, there was an immediate reduction in empiric vancomycin use after the intervention (OR 0.71, 95% CI 0.54-0.95, P=0.02), with no significant change in post-intervention slope. Empiric vancomycin days after suspected SBI onset decreased by 24% immediately after the intervention (IRR 0.76, 95% CI 0.65-0.89, P<0.01), with no significant change in postintervention slope. There were no increases in mortality, organ dysfunction, or missed MRSA infections postintervention. CONCLUSION:A multifaceted stewardship intervention reduced empiric vancomycin without evidence of harm, supporting the safety and feasibility of targeting empiric antibiotic prescribing in the PICU setting.
BACKGROUND:When people develop measles (cases), healthcare facility exposures are common and result in many potentially exposed people requiring resource-intensive control measures. We summarized exposures and transmission among people exposed to measles (contacts) in healthcare settings in New York City (NYC). METHODS:NYC Health Department's surveillance data of NYC contacts exposed to measles cases in any NYC healthcare facility during December 2023-September 2025 was analyzed as a retrospective descriptive study. Characteristics summarized included measles transmission, immunity status, post-exposure prophylaxis (PEP) administration, facility setting, and time of measles exposure. RESULTS:Of 2,122 healthcare contacts to 28 cases, no secondary cases occurred. 1,285 (60.6%) were vaccinated or had other evidence of immunity, 618 (29.1%) were adults with unknown immunity, 124 (5.8%) were not immune and received PEP, and 95 (4.5%) were not immune and did not receive PEP. Most contacts were exposed in emergency departments and/or hospital inpatient settings (1,406; 66.3%). Among 1,028 contacts with known time of exposure (48.4% of all contacts), 785 (76.4%) overlapped with the case in the healthcare facility, 146 (14.2%) arrived within 1 hour and 97 (9.4%) arrived 1-2 hours after the case left or was isolated. CONCLUSIONS:Most contacts exposed to measles in NYC healthcare facilities had presumptive immunity or were adults with unknown immunity. No transmission occurred among 2,122 exposed contacts, including non-immune contacts. Given no secondary transmission and resource-intensive control measures, relying solely on time-based measles exposure definitions may be overly broad. Incorporating strategies like facility air exchange data might better assess transmission risk.
BACKGROUND:Current licensed malaria vaccines are modestly protective against severe Plasmodium falciparum malaria but do not contain components which control blood stage infection. We evaluated the impact of antibodies to three blood stage candidate antigens (PfGARP, PfSEA-1, and PfGBP130) on P. falciparum infection and disease in a longitudinal cohort of children living in a holoendemic region of Western Kenya. METHODS:We enrolled and followed 266 children aged 2 to 7 years living in Western Kenya. Over the course of a 3-year follow-up period, we actively assessed their health status weekly, collected blood samples monthly to assess P. falciparum infection incidence and intensity, and measure IgG antibody levels to blood stage vaccine candidate antigens. RESULTS:Children with high levels of IgG antibodies to PfGBP130 or PfGARP, but not PfSEA-1, experienced 3.4- and 1.9- fold lower parasite densities respectively compared to those with low antibody levels (both P < 0.002). In addition, children with high levels of both anti-PfGBP130 and anti-PfGARP had significantly lower risk of clinical malaria compared to children with low antibody levels (HR: 0.58, 95% CI: 0.85-0.40). Over the 3-year follow-up period, individuals with elevated anti-PfGBP130 and anti-PfGARP antibody levels experienced an average of 4.51 cases of clinical malaria while those with lower levels experienced an average of 7.11 cases of clinical malaria (P = 0.005). CONCLUSIONS:Higher antibody levels to PfGBP130 and PfGARP predict significantly lower parasite densities and lower risks of clinical malaria among 2- to 7-year-old children residing in a holoendemic area of Kenya.
BACKGROUND:Reports of ceftriaxone serious adverse events (SAEs), including deaths, from multiple jurisdictions during December 2024-January 2025 prompted a nationwide investigation to evaluate product safety, characterize SAEs, and assess for changes in baseline adverse event occurrence via national databases. METHODS:In February 2025, CDC issued a national call for cases, defined as SAEs involving death or CPR within six hours of ceftriaxone injection, not otherwise explained and occurring in non-ICU settings during September 2024-August 2025. Epidemiologic and clinical data were collected by health departments and reported to CDC. Laboratory testing of ceftriaxone and lidocaine diluent was performed at FDA. Temporal trends in adverse events (2016-2019 vs 2020-2024) were assessed via Medicare claims and National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System analyses. RESULTS:Among 31 cases identified from 27 healthcare facilities (65% outpatient) across 18 states during September 2024-August 2025, all involving death or CPR, 12 (39%) persons died, 23 (74%) had anaphylaxis-type presentations (65% without skin/mucosal involvement), 21 (68%) had previous ceftriaxone exposure, and 24 (77%) had cardiac comorbidities. Median age was 67 years (IQR: 60-81). Antihypertensive use was common (n=19/28, 68%). Product testing revealed no evidence of tampering, adulteration, endotoxin, or purity/potency issues. National adverse event trends were stable across 2016-2019 and 2020-2024. CONCLUSIONS:SAEs, including deaths, can occur after ceftriaxone receipt. Product testing and trend analyses did not identify evidence of a new safety issue. This investigation highlights the need for ongoing vigilance for ceftriaxone SAEs and reporting to FDA MedWatch.
BACKGROUND:Telemedicine is increasingly used to expand access to infectious diseases (ID) specialists but data on patient outcomes are limited. We compared patient outcomes of inpatient in-person ID consultations and tele-ID in a community hospital. METHODS:One of two community hospitals in our health system transitioned from in-person to telehealth ID consultation (tele-ID). We examined a retrospective cohort of patients receiving ID consultations in both hospitals before and after the transition while accounting for secular trends. RESULTS:A total of 3,223 patients received ID consultation in the telemedicine switch hospital (1,682 during the in-person period and 1,541 during the tele-ID period). Length of stay among patients receiving ID consultation did not differ between the pre-telehealth and telehealth periods (median 7 (IQR 4-13) vs. 7 (IQR 5-13) days, p=0.47). Similarly, 30-day readmission (17.4% vs. 17.7%, p=0.86), 30-day mortality (9.2% vs. 8.7%, p=0.65), and combined 30-day death/readmission (25.9% vs. 25.6%, p=0.88) did not differ between the pre-telehealth and telehealth periods. Multivariable modeling adjusting for age, sex, race, modified Charlson score, and hospital demonstrated no significant associations between receiving tele-ID care and 30-day readmission, death, or days dead/hospitalized within 90 days after the initial ID consultation. The mean number of computed tomography/magnetic resonance imaging studies during the index admission was significantly higher at the telehealth switch hospital during the telehealth period (2.28) than the pre-telehealth period (1.69, p<0.001 for comparison). CONCLUSIONS:Transition to tele-ID was not associated with any increase in patient-relevant adverse outcomes but was associated with increased imaging utilization.
BACKGROUND:Both piperacillin-tazobactam and cefepime are widely used for the treatment of pneumonia caused by Pseudomonas aeruginosa. Despite this, no studies have directly compared these agents for this purpose. METHODS:We performed a single-center retrospective cohort study of patients with pneumonia caused by P. aeruginosa treated with piperacillin-tazobactam or cefepime. The co-primary outcomes were 30-day mortality and a 30-day desirability of outcome ranking (DOOR) incorporating clinical failure, resistance, acute kidney injury (AKI), and recurrence. Overlap-weighted (OW) analyses were used to account for confounding. RESULTS:A total of 204 patients (piperacillin-tazobactam, n = 117; cefepime, n = 87) were included. Baseline characteristics were comparable between groups after OW. All-cause mortality occurred more frequently in patients who received piperacillin-tazobactam (23.1%) compared with those receiving cefepime (11.5%; p = 0.04, OW odds ratio 2.38, 95% CI 1.05-5.42). Conversely, no significant difference in the DOOR endpoint associated with receipt of piperacillin-tazobactam (46%, 95% CI 39% - 53%) was demonstrated. Rates of resistance development (12.0% vs 5.7%, p = 0.15; OW subhazard ratio 2.25, 95% CI 0.79-6.43), and clinical success (65% vs 70%; OW odds ratio 0.81, 95% CI 0.43-1.51) were similar amongst patients receiving piperacillin-tazobactam and cefepime, respectively. AKI incidence on study drug was likewise similar (7.0% vs 7.2%). CONCLUSION:In this comparative study of cefepime and piperacillin-tazobactam for P. aeruginosa pneumonia, increased risk of mortality was seen with piperacillin-tazobactam. No differences were seen in other key outcomes, although sample size limits interpretation. This finding warrants further investigation in larger studies.
BACKGROUND:Individuals with COVID-19 who have underlying renal or hepatic comorbidities are at a higher risk of mortality than those without these comorbidities. Real-world data on the effectiveness of early remdesivir (RDV) initiation in these populations are limited. This study evaluated the effect of early RDV initiation on 28-day all-cause in-hospital mortality among patients in the US who were hospitalized for COVID-19 and had renal or hepatic comorbidities. METHODS:This retrospective comparative effectiveness study used patient-level medical claims and hospital chargemaster data in the US (2021-2025). Adults who received early RDV were compared with those who did not. Patients were stratified by supplemental oxygen use in the first 2 days of hospitalization. The primary endpoint was risk of 28-day all-cause in-hospital mortality, estimated using Cox proportional hazards models. RESULTS:After 1:1 propensity score matching, 22,378 patients were included in the renal cohort (11,189 per group) and 5026 patients were included in the hepatic cohort (2513 per group). There was a reduced risk of 28-day all-cause in-hospital mortality with early RDV in both the renal cohort (HR: 0.75 [95% CI: 0.68, 0.83]; P <0.01) and the hepatic cohort (HR: 0.76 [95% CI: 0.60, 0.95]; P = 0.02). The risk of mortality was significantly lower with early RDV initiation among patients who received supplemental oxygen in both cohorts and among patients in the hepatic cohort who did not receive supplemental oxygen. CONCLUSION:Early RDV initiation was associated with improved survival among patients with renal or hepatic disease who were hospitalized for COVID-19.
BACKGROUND:Long-acting injectable cabotegravir plus rilpivirine (LA CAB+RPV) is approved for virally suppressed people with human immunodeficiency virus (HIV), but evidence for its use in those with persistent viremia and adherence challenges remains limited. METHODS:We conducted a multicenter, open-label, randomized study involving oral antiretroviral therapy (ART)-experienced people with HIV who had been diagnosed with HIV for at least 12 months and a most recent HIV-1 RNA level of at least 200 copies per milliliter. Participants with resistance-associated mutations to CAB or RPV were excluded. Eligible participants were randomly assigned in a 1:1 ratio to receive immediate LA CAB+RPV or to continue standard oral therapy until Week 24 (delayed switch group). The primary endpoint was the proportion of participants with an HIV-1 RNA level of less than 200 copies per milliliter at Week 24. RESULTS:Of 61 randomized participants, 45 met eligibility criteria and were included in the analysis; 91% were male, and the median baseline HIV-1 RNA was 35,000 copies/mL. At Week 24, viral suppression was achieved in 88.0% (22/25) in the immediate LA group versus 55.0% (11/20) in the delayed switch group (relative risk for failure to achieve viral suppression, 0.27; 95% CI, 0.08-0.86; p = 0.026). The effect of LA CAB+RPV was sustained through Week 52. CONCLUSIONS:Among people with HIV and viremia associated with adherence challenges, immediate initiation of LA CAB+RPV resulted in higher rates of viral suppression than continued oral ART, supporting its use beyond populations with stable suppression.
BACKGROUND:Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) is an effective HIV treatment, but barriers, such as financial considerations limit implementation. Understanding the real-world financial impact is essential for program sustainability and equitable access. METHODS:This retrospective cohort study at the University of Nebraska Medical Center, Specialty Care Center (May 2022 to December 2024) evaluated people with HIV (PWH) receiving LAI CAB/RPV via buy-and-bill acquisition. We assessed annual staff time, program income (PI), and patient costs (PC). The primary endpoint was annual PI adjusted for staff time per patient compared to a modeled oral antiretroviral therapy (ART) comparator (bictegravir/emtricitabine/tenofovir alafenamide) using Wilcoxon Signed-Rank test. PI and PC were compared across study years and payer mix with Kruskal-Wallis test. Multivariate regression models explored factors predicting PI losses. RESULTS:The study included 110 PWH receiving 862 injections. LAI CAB/RPV required more annual staff time per participant than oral ART (7.4 hours vs. 3.7 hours). Median annual PI per participant hour managed was significantly lower for LAI CAB/RPV versus oral ART model across all study years (p<0.001). Despite this, the LAI program remained financially viable (median PI of $2,163/injection) with minimal PC; 91% of injections had $0 cost-sharing. PI losses occurred in 4.9% of injections and was associated with Medicaid coverage, lack of AIDS Drug Assistance Program (ADAP) coverage, and insurance changes. CONCLUSIONS:Although LAI CAB/RPV requires double the staff time and generates less time-adjusted PI than oral ART, buy-and-bill LAI programs can remain financially viable. Payer mix and insurance stability are essential to ensuring sustainability and equitable access.
