Open Forum Infectious Diseases最新文献

Background: People living with HIV (PLWH) make up a significant proportion of the population in sub-Saharan Africa, and there exists a significant gap in research on the burden and associated risk factors for extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in this population. We describe the risk factors associated with ESCrE colonization in nonhospitalized PLWH.

Methods: This is a secondary data analysis of nonhospitalized adult PLWH included in a regional surveillance cohort study describing colonization with ESCrE in Botswana. Participants underwent rectal swab sampling to identify ESCrE. Bivariate and multivariable analysis was used to determine risk factors associated with ESCrE colonization.

Results: A total of 546 adult PLWH were recruited over 3 districts and were included in this analysis. The mean (standard deviation) age was 42 (10.4) years, and 448 (82.1%) were women. Our findings demonstrated that 27.3% (149/546) of participants screened positive for ESCrE rectal colonization. Independent risk factors {adjusted odds ratio (aOR) [95% CI]} for ESCrE colonization included recent hospitalization (3.37 [1.13-9.98]), at least 1 household member with ESCrE colonization (1.74 [1.01-3.00]), and recruitment before the countrywide COVID-19 lockdown (2.01 [1.33-3.04]). Recent antibiotic use had an elevated OR for ESCrE colonization that did not achieve statistical significance in the adjusted analysis (aOR: 1.84 [.92-3.68]).

Conclusions: Hospitalization and colonization of other household members with ESCrE are important factors associated with colonization with ESCrE, as seen in other populations. The prevalence of ESCrE following the COVID-19 lockdown was significantly lower, suggesting the presence of factors that were protective against colonization. It is unclear how long these effects lasted.

Objective: To compare clinical outcomes of patients treated with liposomal amphotericin B (L-AmB) versus mold-active triazoles as primary treatment for invasive aspergillosis (IA).

Methods: Retrospective study of adult patients treated with either L-AmB or triazoles for proven or probable IA at 2 academic hospitals over a 10-year period. The primary endpoint was all-cause 90-day mortality from IA diagnosis. Landmark trial emulation at day 7 postdiagnosis was used to compare initial triazole versus L-AmB for IA. Confounding by indication was addressed using inverse probability of treatment weighting (IPTW) with stabilized weights, and treatment effects were estimated using Cox regression with both IPTW and covariate adjustment.

Results: Overall, 401 patients were included. Median age 65 (interquartile range 56-74) years, 60.8% male. Main predisposing conditions were: hematologic malignancy 151 (37.7%), severe respiratory viral infection 120 (29.9%), and chronic steroid treatment 64 (16%). Overall, 105 (26.2%) patients received L-AmB and 296 (73.8%) triazoles as initial therapy. Patients on L-AmB were more likely to have therapy changed (63.8% vs 17.2%, P < .001) for switching to oral triazoles (48, 71.6%), while the main reason for changing triazoles was adverse events (23, 45.1%). Overall 90-day survival rates were similar between triazole (58.8%; 95% confidence interval [CI], 53.4-64.7) and L-AmB (53.3%, 44.6-63.8) groups (P = .3). IPTW-weighted Kaplan-Meier survival curves from day 7 landmark demonstrated an adjusted hazard ratio of 1.43 (95% CI, 0.87-2.33; P = .61).

Conclusions: Primary L-AmB therapy was well tolerated and associated with similar survival rates as triazoles. Further studies are needed to investigate the impact of primary L-AmB on IA patient outcomes.

[This corrects the article DOI: 10.1093/ofid/ofaf792.].

Background: The proportion of multidrug-resistant tuberculosis (MDR-TB) cases is increasing in Bhutan. We conducted the first retrospective genomic-epidemiological study to provide insights into the population structure, resistance patterns, and recent transmission in Bhutan.

Methods: Whole genome sequencing was performed on randomly selected drug-resistant (DR-TB) and drug-sensitive TB (DS-TB) isolates from Bhutan, collected between 2018 and 2022 at the Microbiological Diagnostic Unit Public Health Laboratory in Melbourne, Australia. Bioinformatic analysis was performed to identify drug-resistance mutations and genomic clustering of cases.

Results: Approximately 40% of DR-TB and 2.5% of DS-TB were sequenced each year. Of the 203 sequences that passed the quality control, 126 (62.1%) were MDR-TB and 15 (7.4%) were isoniazid-resistant TB. There were 4 different circulating lineages, with the majority belonging to lineage 2 (86.2%). Using a SNP-threshold of ≤12 SNPs, 71% of sequences formed 12 genomic clusters; the largest comprised 88% of all MDR-TB sequences and spanned the entire study period and the country. These cases were highly clonal, with a mean pairwise SNP distance of 10 (range 0-25). Phylogenetic analysis with publicly available international sequence data showed that this MDR-TB cluster formed a distinct clade.

Conclusions: Contrary to current assumptions of repeat importations, the major burden of MDR-TB in Bhutan appears to be due to recent local transmission resulting in a large endemic cluster, advocating for targeted and enhanced contact tracing and screening for this MDR-TB clade. This study highlights the significant value of investing in TB genomics in resource-limited settings to gain actionable insights to inform policy decisions.

Background: The global macroeconomic impact of Tuberculosis (TB) lacks comprehensive quantification using standardized economic frameworks.

Methods: This analysis utilized data from the Global Burden of Disease (GBD) 2021 to assess the economic burden of TB through the lens of the Value of a Statistical Life Year (VSLY) framework, integrating willingness-to-pay-based economic measures. The study monetized the total disability-adjusted life years (DALYs) associated with TB to estimate overall welfare losses. Country-specific gross domestic product (GDP) data, adjusted for purchasing power parity (PPP), were sourced from the World Bank and integrated with DALY estimates to calculate the Value of Lost Welfare (VLW).

Results: In 2021, the global economic cost of TB, expressed as VLW, was estimated at US$1.98 trillion (95% uncertainty interval [UI]: 1.62, 2.45), representing 1.29% (95% UI: 1.05, 1.60) of global GDP. The economic impact of TB was disproportionately distributed across regions, with countries of low Socio-Demographic Index (SDI) facing the most severe burden, where VLW represented 7.83% (95% UI: 5.70, 11.20) of GDP. Lower-middle SDI regions experienced a VLW impact of 5.28% (95% UI: 4.30, 6.58). Sub-Saharan Africa (US$406.2 billion; 8.40% of GDP) and South Asia (US$822.5 billion; 5.70% of GDP) were identified as the most economically affected super-regions. India bore the highest absolute economic burden (US$477.5 billion). In contrast, high-SDI countries demonstrated a VLW-to-GDP ratio of just 0.10% (95% UI: 0.09, 0.12).

Conclusions: Prioritizing TB control in economic policy is urgently needed. Equitable resource allocation to high-burden regions is vital to alleviate the disease's economic consequences and improve global health.

Background: Despite increased access to antiretroviral therapy (ART) for women with HIV (WWH), poor postpartum HIV care retention persists. This analysis evaluates Intimate Partner Violence (IPV) and ART adherence in pregnant WWH.

Methods: We analyzed secondary data from a US behavioral intervention trial to improve postpartum retention in WWH. Data were collected from the baseline survey including the Edinburgh Postnatal Depression Scale (EPDS), adverse childhood experiences (ACE), and HIV-related stigma scores, and the WHO Violence Against Women questionnaire to assess IPV. A multivariable logistic regression examined associations between IPV timing (before, during pregnancy, any) and type (physical, psychological, sexual) and ART adherence (≥80% ART doses in the prior month).

Results: A total of 137 pregnant WWH enrolled between March 2020 and March 2024 were included: mean age was 30.5 (SD 5.6); 83% were Black, 14% Hispanic; mean number of pregnancies was 3.3 (SD 2.1). Depression, stigma, and ACEs were prevalent: EPDS scores of ≥10 were seen in 45% of women, ≥4 ACEs in 23%, and 51% reported HIV-related shame. Forty women (29%) reported IPV exposure. Higher EPDS, ACE, and stigma scores were seen in women exposed to IPV (P < .02). Physical IPV during pregnancy had the strongest association with decreased ART adherence in pregnancy (adjusted odds ratio = 0.10, P = .02). Psychological IPV and any IPV type during or before pregnancy were also associated with lower odds of adherence.

Conclusions: We found high IPV rates and a significant negative association with ART adherence among pregnant WWH highlighting the importance of addressing IPV in HIV care.

Background: Efforts to improve inpatient antibiotic prescribing are limited by a lack of insight into the complicated decisions around antibiotic use. We aimed to explore antibiotic therapeutic decision making among internal medicine resident physicians.

Methods: We performed a qualitative study with a constructivist paradigm employing semistructured in-person focus groups of internal medicine trainees at a teaching hospital system from December 2023 through January 2024. Two researchers independently performed a thematic analysis of focus group transcripts. We resolved discrepancies through in-depth discussion, negotiated consensus, and converged codes into overarching themes.

Results: Twenty-five residents participated across 3 focus groups. Residents identified a general approach to prescribing empiric antibiotics, including triaging critical illness and identifying the presence of infection, the source of infection, the antibiotic that covers the likely pathogens, and relevant patient-specific factors. Empiric choice was modulated by 3 subthemes: institutional culture, antibiotic stewardship policies, and clinical resources. Major challenges in therapeutic decision making included navigating uncertainty, fear of clinical deterioration, difficulty determining appropriate antibiotic duration/spectrum, and the inconsistency of clinical reasoning by supervising attendings. Certain safety net strategies were used to mitigate this uncertainty. Residents felt that their confidence in antibiotic prescribing decisions improved over time through experience, especially on overnight rotations. Infectious diseases physicians and pharmacists provided education and a needed model approach for therapeutic reasoning and supported residents in increasing their risk tolerance.

Conclusions: This study provides insights into resident decision making regarding antibiotic use, which may inform educational interventions to optimize antibiotic utilization and adherence to practice guidelines at teaching hospitals.

Background: Delayed HIV diagnosis and treatment may increase the risk of developing dementia later in life. We evaluated whether low CD4 count (<200 cells/µL) prior to first known use of antiretroviral therapy (ART)-a proxy for delayed HIV diagnosis or treatment-was associated with risk of age-associated dementia.

Methods: We conducted a retrospective cohort study (2000-2023) among U.S. adults with HIV aged ≥50 years, all on ART and dementia-free at baseline. The exposure of interest was low pre-ART CD4 count. Dementia diagnoses were identified via electronic health records. The association of low pre-ART CD4 with incident dementia was evaluated using Fine-Gray subdistribution hazard models, accounting for the competing risk of death and adjusting for sociodemographic and clinical confounders. Sub-analyses examined dementia risk among individuals who had low pre-ART CD4 but demonstrated CD4 recovery to ≥500 cells/µL after ART initiation.

Results: Among 21 354 people with HIV on ART (mean age 54; 87% men; 46% White, 23% Black, 21% Hispanic, 4% Asian), 30% had pre-ART CD4 < 200 cells/µL. Over a mean follow-up of 7 years, 618 were diagnosed with dementia. Low pre-ART CD4 was associated with greater risk of dementia (adjusted hazard ratio [aHR]: 1.33, 95% CI: 1.13-1.57). CD4 recovery with ART attenuated but did not eliminate dementia risk (aHR: 1.17, 95% CI: 0.85-1.60).

Conclusions: Low CD4 count prior to ART-reflecting delayed HIV diagnosis or treatment-was associated with higher dementia risk. Continuing assertive HIV screening and prompt ART initiation in the community will be important to support long-term cognitive health in people with HIV.

In this systematic literature review and meta-analysis, real-world data from high-income economies (excluding the US and Africa) on HIV-1 epidemiology (2019-2023), oral pre-exposure prophylaxis (PrEP) effectiveness (2017-2023), and prevalence of oral PrEP use (2017-2023) were assessed in key populations disproportionately affected by HIV-1. Overall, 204 unique data sources were identified from 38 high-income economies. In key populations, the pooled global HIV-1 prevalence estimate was 5.1% (95% confidence interval: 4.2%-6.1%), ranging from 0.2% in South Korea to 28.9% in Romania. Pooled global prevalence was lowest in transgender men (1.4%) and people in prison (2.2%); 7.0%-7.8% in men who have sex with men, people who inject drugs, sex workers, and transgender women; and highest in individuals who were in multiple key populations (19.4%). Global prevalence of oral PrEP use was 18.2% among key populations, with HIV-1 prevalence <0.4% in PrEP users, indicating high PrEP effectiveness. Targeted prevention strategies are needed to provide global equitable PrEP access and reduce HIV-1 acquisition.