Open Forum Infectious Diseases最新文献

Background: We aimed to examine the epidemiology and outcomes of AdV disease in SOTr and assess the utility of AdV surveillance in SOTr <13 years.

Methods: SOTr transplanted at Rigshospitalet, 2010-2021, were included. The center had a screening program for SOTr <13 years with monthly plasma AdV tests the first 6 months following transplantation.

Results: We included 2009 SOTr (of whom 82 were aged <13 years), and 1330 blood samples from 382 SOTr were analyzed for AdV, of which 10 (0.8%) from 6 SOTr <13 years tested positive. Five out of six were tested as part of the screening program. Three remained asymptomatic, while three had symptoms attributable to co-infections. One adult lung transplant recipient with AdV in BAL had acute exacerbation of chronic graft rejection.

Conclusions: We found a low incidence of AdV disease. SOTr diagnosed with AdV viremia as part of screening remained asymptomatic or had symptoms attributable to co-infections. Our findings do not support routine surveillance for AdV in SOTr.

Background: Shigella spp are among the notable causes of global diarrheal disease and death, accounting for 13.2% of deaths in 2016. Antimicrobial resistance complicates shigellosis management. Understanding local disease epidemiology is crucial for developing effective preventive strategies, including vaccine use.

Methods: We investigated antimicrobial resistance, risk factors (socioeconomic, behavioral, and water, sanitation and hygiene (WaSH), and clinical characteristics of Shigella diarrhea in Mukuru informal settlement and surrounding villages in Nairobi, Kenya. Patients presenting with diarrhea, fever, or both in treatment centers had stool or rectal swab samples cultured, and bacteria was identified through biochemical and serologic tests.

Results: The rate of Shigella isolation among the 4689 individuals presenting with diarrhea was 1.4% across all ages, with a similar isolation rate (1.5%) among children <5 years of age. The majority of the Shigella spp (40 [59.7%]) were Shigella flexneri, and the majority of S flexneri (34 of 40 [85%]) were resistant to trimethoprim-sulfamethoxazole; however, all were sensitive to amoxicillin-clavulanate, ceftazidime, ceftriaxone, and cefpodoxime. The rate of multidrug resistance was higher in Shigella sonnei (13 [48.1%]) than in S flexneri (3 [7.5%]). Shigella positivity was associated with bloody diarrhea, severe/moderate dehydration, coated tongue, and high fever. Consumption of street food was also associated with Shigella diarrhea.

Conclusions: Despite low prevalence, shigellosis still poses a significant burden of diarrheal disease, warranting future incidence studies. First-line antibiotics against Shigella remain effective, but intermediate resistance to azithromycin and ciprofloxacin is a concerning trend. Improving household food preparation and handling could potentially reduce Shigella infections.

Multiple observational studies in methicillin-resistant Staphylococcus aureus and enterococcal infections have suggested that higher doses of daptomycin may be associated with better clinical outcomes. However, optimal daptomycin dosing in methicillin-sensitive S aureus bloodstream infections remains unclear. In this multicentered, retrospective, observational cohort study, we compared standard dose daptomycin (<8 mg/kg) vs high dose (≥8 mg/kg) for methicillin-sensitive S aureus bloodstream infections. In a propensity-weighted model, the composite outcome of treatment failure within 90 days was lower in the high-dose group relative to the standard dose group (odds ratio, 0.496; 95% CI, .306-.804). We did not detect any significant difference in safety outcomes.

We compared the performance of 2 multiplex platforms, Luminex xTAG Gastrointestinal Pathogen Panel and TaqMan Array Card, against a panel of 14 enteric pathogen targets in a community-based birth cohort in Ecuador. We found high levels of agreement and similar prevalence estimates across most pathogens.

Background: It is generally believed that HIV-1 capsid inhibitor-naïve populations are susceptible to capsid inhibitors. Moreover, conventional HIV-1 resistance genotyping does not include the CA region, leading to limited surveillance data.

Methods: We conducted a retrospective study to investigate the presence of mutations at positions associated with capsid inhibitor resistance before the introduction of the first HIV-1 capsid inhibitor, lenacapavir, in Taiwan. Capsid mutations at positions L56, N57, M66, Q67, K70, N74, A105, and T107 were analyzed using a local HIV-1 database that encompasses near-full-length next-generation sequencing data of both antiretroviral therapy (ART)-naïve and -experienced individuals with HIV-1, collected between 2017 and 2023 in Northern Taiwan.

Results: A total of 287 CA sequences were analyzed. Mutations at positions associated with capsid inhibitor resistance were rare, found in 4.5% (7/156) of ART-naïve and 5.3% (7/131) of ART-experienced individuals, mainly as accessory mutations or polymorphisms. Notably, a Q67H mutation was found in an ART-naïve individual at a frequency of 26.8%, while a Q67R mutation, with unclear clinical implications, appeared at 2.8% in an ART-experienced case.

Conclusions: This result indicated low prevalence yet undeniable existence of naturally occurring capsid inhibitor resistance-related mutations in capsid inhibitor-naïve individuals with HIV-1.

Background: Specialty societies, including the Infectious Diseases Society of America, strive to address gender and racial inequities in professional advancement. Microaggressions remain a persistent and pervasive barrier to these goals. Nonprofessional speaker introductions are a manifestation of race- and gender-based microaggressions, which have not been previously assessed at IDWeek. We assessed disparities in speaker introductions at IDWeek over a 7-year period that included formal gender equity initiatives introduced in 2016.

Methods: We conducted a retrospective observational study of video-recorded IDWeek speaker introductions from 2013 to 2019. Trained coders reviewed presentation video archives to assess a primary outcome of nonprofessional introductions: when a speaker's professional title was not used as the first introduction. We used descriptive statistics, Fisher exact tests, Cochrane-Armitage trend tests, and multivariable logistic regression to characterize relationships between speaker introductions and presentation year, speaker demographics, and speaker-moderator demographic concordance.

Results: Of 1940 videos reviewed, 48.9% of IDWeek speakers received nonprofessional introductions during and before 2016 vs 41.5% of speakers after 2016 (P = .0013). There was an increasing linear trend in the frequency of professional introductions by speaker age group from 47.1% for age <40 years to 65.3% for age >60 years (P < .0001). White moderators more frequently used nonprofessional introductions than moderators from backgrounds underrepresented in medicine (47.7% vs 29.1%, P = .0014). Women-men speaker-moderator pairs had more nonprofessional introductions (54.6%, P < .001).

Conclusions: In the largest assessment of microaggressions in speaker introductions at a national medical specialty conference, we highlighted some progress over time and ample opportunity to further standardize equitable speaker introductions, especially for women and junior speakers.

Prompt confirmation of human immunodeficiency virus (HIV) is critical. We examined 10 years of discordant results without reflex HIV RNA. Of patients with acute HIV infection, 43.9% (95% confidence interval, 36.2%-52.0%) had confirmation delays >30 days or were never confirmed, indicating a need for reflex RNA to facilitate diagnosis.

Background: National US data on the burden and risks for hepatitis C virus (HCV) infection in people with human immunodeficiency virus (HIV) during the direct-acting antiviral (DAA) era are limited. These data are important to understand current progress and guide future efforts toward HCV microelimination.

Methods: We evaluated (1) HCV prevalence (2011-2013, 2014-2017, 2018-2022) using a serial cross-sectional design and (2) correlates for HCV viremia (2018-2022) in adult people with HIV (PWH) within the Centers for AIDS Research Network of Integrated Clinic Systems (CNICS) cohort using multivariable adjusted relative risk regression. The most recent data from each time period were used for calculations and models.

Results: In the CNICS cohort, HCV viremia prevalence was 8.7% in 2011-2013, 10.5% in 2014-2017, and 4.8% in 2018-2022. Disparities in prevalence across demographic groups defined by age, gender, and race/ethnicity were smaller in 2018-2022 than earlier time periods. In relative risk regression, female gender, detectable HIV RNA, higher proportion of missed visits (last 18 months), higher FIB-4 score, higher depressive symptom severity, and current use of methamphetamine and illicit opioids were associated with HCV viremia in 2018-2022.

Conclusions: The prevalence of HCV viremia during the DAA era in this US-based national cohort of PWH improved over time and across demographic subgroups but remains higher than those without HIV. Our findings highlight the continued importance of prioritizing HCV care in all PWH, especially in certain key, less-reached groups. Proactive, comprehensive efforts to care engagement, substance use, mental health, and other social determinants will be crucial to improve reach, prevention, and treatment to achieve HCV elimination goals.

Background: Breakthrough invasive mold infections (bIMIs) are life-threatening complications in hematologic cases. Most previous studies in this field covered the whole spectrum of fungal pathogens, including yeasts, and antifungal agents.

Methods: We conducted a retrospective study including all hematologic cases of patients diagnosed with a bIMI while receiving a mold-active antifungal agent at our center between January 2017 and June 2022.

Results: Overall 37 patients were diagnosed with bIMI: 6 (16.2%) proven, 18 (48.6%) probable, and 13 (35.1%) possible. The highest incidence rate was found for micafungin (1.31 bIMI episodes per 1000 treatment-days), although with no significant differences across antifungal agents. Most patients (90.9%) for whom therapeutic drug monitoring was performed exhibited adequate through levels. Ten (27.0%) patients had undergone allogeneic hematopoietic stem cell transplantation. Aspergillus species was the most common pathogen in cases with microbiological identification. Regarding risk factors, 67.6% had severe neutropenia at diagnosis and 40.5% had received high-intensity chemotherapy. Rates of clinical response and attributable mortality by day +30 were 64.9% and 23.3%, respectively. Poorer performance status, higher Charlson Comorbidity index, older age, and higher C-reactive protein by day +7 were associated with 30-day attributable mortality.

Conclusions: Aspergillus was the predominant pathogen in our cohort of bIMIs, with a significant proportion of episodes occurring despite adequate triazole levels. Thirty-day attributable mortality was lower than previously reported. Poorer performance status, higher comorbidity burden, and older age had a relevant role in the outcome of bIMI.

Background: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

Methods: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.

Results: Study enrollment was halted early, prior to reaching the targeted recruitment, and was not powered to detect a decrease in COVID-19 frequency. Symptomatic COVID-19 occurred in 21 of 263 and 10 of 266 participants in the BCG and placebo arms, respectively (P = .50, Fisher exact test). Participants vaccinated with BCG, but uninfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrated increased coronavirus vaccine immunity (increase spike-inducible levels of tumor necrosis factor, interleukin 6, and interleukin 1β) 12 months after BCG vaccination compared to participants receiving placebo. Immune responsiveness to SARS-CoV-2 antigens correlated with BCG-induced DNA methylation changes.

Conclusions: Due to early study closure, the study was not powered to evaluate COVID-19 frequency. Secondary analysis demonstrated that 12 months following vaccination, BCG increased coronavirus vaccine immunity compared to those who did not receive BCG. This increase in COVID-19 vaccine immunity correlated with BCG-induced DNA methylation changes.