Open Forum Infectious Diseases最新文献

Background: Antimicrobial resistance (AMR) is a major global health threat, with a disproportionate impact on low- and middle-income countries. The TEACH PROA-ECHO (Telementoring, Equity & Advocacy Collaboration for Health through Antimicrobial Stewardship) initiative aimed to strengthen antimicrobial stewardship programs (ASPs) in Latin America using the ECHO telementoring model.

Methods: From March to December 2024, 80 healthcare institutions from 10 Latin American countries participated in biweekly telementoring sessions focused on case-based learning guidance on stewardship interventions and collaborative problem-solving related to antimicrobial prescribing and surveillance. A validated self-assessment tool was used to categorize baseline ASP development and monitor progress over time. Learning activities were evaluated using Moore's framework, and participating teams identified local barriers and enablers for stewardship activities.

Results: Of the 80 institutions, 73 (91%) completed the program. A total of 322 professionals were registered in the project, accounting for 2166 attendances. Moore's indicators showed high satisfaction (Net Promoter Score 79) and significant knowledge improvement after sessions (97.3% vs 81.4%; P < .0001). Mean ASP self-assessment scores increased from 53.1 to 64.0 (P < .0001). The proportion of institutions with intermediate or advanced ASP development rose from 56.2% to 83.6% (P < .001). Higher baseline scores were associated with for-profit institutions, ASP implementation longer than 5 years, and program continuity (lack of ASP interruptions in the last 5 years).

Conclusions: Telementoring is an effective and scalable approach to strengthening antimicrobial stewardship in Latin America. The TEACH PROA-ECHO model represents a valuable strategy to support national AMR action plans in resource-limited settings.

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: Ocular candidiasis (OC) is a notorious complication of candidemia, but guidelines on fundoscopic screening are inconsistent. We aimed to determine the frequency of OC in patients with candidemia who underwent fundoscopy, regardless of visual symptoms, and to evaluate its impact on antifungal treatment selection and duration.

Methods: A retrospective cohort study was performed at 2 tertiary care hospitals in the Netherlands in adult patients with at least 1 positive blood culture with Candida species between January 2018 and December 2024. Primary outcomes were the incidence of OC (defined as proven or probable chorioretinitis or endophthalmitis), persistent vision loss, and changes in the choice and/or duration of antifungal therapy in patients with OC.

Results: Of 402 patients, 307 (76.4%) underwent fundoscopy. Ocular candidiasis was diagnosed in 15 of 307 patients (4.9%), including 12 with probable chorioretinitis (3.9%) and 3 with probable endophthalmitis (1.0%). Nine of the 15 patients (60%) were asymptomatic (n = 6) or unable to report symptoms (n = 3). In all 15 patients, the fundoscopic findings resulted in a change in therapy. This consisted of therapy prolongation (n = 15), addition of (n = 7) or switch to (n = 4) an azole, and intravitreal antifungal injections (n = 2). Persistent visual impairment of any degree occurred in 3 of 15 patients (20%), all of whom were initially symptomatic.

Conclusions: Ocular candidiasis is a relatively rare but clinically significant complication of candidemia. Fundoscopic findings are used to guide treatment decisions. Persistent vision loss was uncommon.

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.

Background: Current Mycosis Study Group Education and Research Consortium (MSGERC) and European Confederation of Medical Mycology (ECMM) response criteria for clinical trials often fail to comprehensively assess outcomes of the total patient experience, prompting the need for innovative methodologies.

Methods: Utilizing a modified Delphi process, members of MSGERC and ECMM were sent a series of surveys utilizing an online platform. Except for the first survey, participants' responses remained anonymous to the steering committee. The first survey was elaborated based on expert opinion, with each subsequent round building upon the responses from previous rounds. Agreement was predefined by consensus of the steering committee as majority support, set at >70% agreement, for each survey component.

Results: For invasive candidiasis, a composite of treatment failure and infectious complications were included to elaborate a DOOR scale, with endpoints measured at 2 weeks after initiation of therapy. For invasive aspergillosis, a composite of treatment failure, presence of disease-attributable complications, and treatment-related adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 weeks after initiation of therapy. For cryptococcosis, a composite of treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 4 weeks after initiation of therapy. For mucormycosis, treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 and 12 weeks after initiation of therapy.

Conclusions: Consensus endpoints were developed for invasive candidiasis, invasive aspergillosis, cryptococcosis, and mucormycosis for use in clinical trials.

Background: We compared the effectiveness and safety profiles of doravirine, lamivudine, tenofovir disoproxil fumarate (DOR/3TC/TDF) with bictegravir, emtricitabine, tenofovir alafenamide fumarate (BIC/FTC/TAF) in people with HIV (PWH) who had achieved virological suppression on efavirenz (EFV)-based antiretroviral regimens.

Methods: This study was a single-center, real-world, prospective observational cohort study. The main inclusion criteria: PWH aged ≥18 years who had received an EFV-containing regimen for ≥6 months and achieved confirmed virological suppression. Participants were stratified according to clinical decisions to switch to DOR/3TC/TDF or BIC/FTC/TAF. The primary effectiveness end point was the proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48, with a preset 4% noninferiority margin.

Results: A total of 349 participants received at least 1 dose of study drugs (142 in DOR group, 207 in BIC group). At 48 weeks, 2 (1.4%) in the DOR group and 1 (0.5%) in the BIC group had HIV-1 RNA ≥50 copies/mL (estimated treatment difference [ETD], 1.0%; 95% CI, -1.6% to 3.7%), establishing noninferiority. In the BIC group, mean CD4 counts decreased significantly by ∼76.5 cells/µL at week 48 (95% CI, -111.801 to -41.218; P < .001) compared with baseline. Over 48 weeks, adverse event rates were comparable between the 2 groups (P = .758). At week 48, the BIC group exhibited a baseline-adjusted mean increase of 0.269 mmol/L in total cholesterol (TC) and 0.171 mmol/L in low-density lipoprotein cholesterol (LDL-C), while the DOR group demonstrated a mean reduction of 0.453 mmol/L in triglycerides (TG), 0.412 mmol/L in TC, and 0.241 mmol/L in LDL-C relative to baseline. All β values for the group-time interaction terms were negative (P < .001). The change in body weight from baseline to week 48 in the DOR group was 1.8 kg lower than that in the BIC group (95% CI, -2.474 to -1.114; P < .001).

Conclusions: In previously virologically suppressed PWH on an EFV-based regimen, the switch to DOR/3TC/TDF maintained virological suppression noninferior to that of BIC/FTC/TAF, with favorable metabolic profiles.

Parasitic infections are often perceived as diseases of low-resource countries, yet they impose a significant and overlooked burden in the United States-especially among immigrants, low-income individuals, and other marginalized populations. This perspectives article examines the case of Mr. X, a landscaper in Houston diagnosed with neurocysticercosis, who faced unaffordable drug costs despite the availability of effective, off-patent treatments. Through his story, we explore the broader issue of pricing for commonly and not-so-commonly prescribed antiparasitic medications, highlighting the role of systemic market failures, regulatory hurdles, and restrictive assistance programs in limiting access to care. The consequences of incomplete treatment include long-term disability, public health risks, and deepened health disparities. We propose policy solutions, including reforms to the Orphan Drug Act, expansion of Medicare negotiation powers, and investment in public-interest drug production, to improve affordability and ensure equitable access to essential antiparasitic drugs.

Background: People with HIV-associated cryptococcal antigenemia are at high risk for meningitis and death. In resource-limited settings, lumbar puncture to evaluate for meningitis is infrequently performed in asymptomatic individuals; therefore, symptomatic individuals are prioritized. We evaluated the predictive value of meningeal symptoms for cryptococcal meningitis in people with cryptococcal antigenemia.

Methods: We conducted a secondary analysis from 3 randomized clinical trials conducted in Uganda between 2017 and 2024. We included adults with meningeal symptoms who had cerebrospinal fluid cryptococcal antigen (CrAg) testing performed. Logistic regressions and classification trees were used to determine the associations between meningeal symptoms and meningitis. Area under the receiver operating characteristic curve (AUROC) and misclassification rate were used to evaluate model performance.

Results: Among 344 participants, median CrAg titer was 1:1280 (interquartile ratio, 1:100-1:2560). Overall, 285 (83%) presented with headache and 205 (60%) participants had meningitis. Presence of headache was associated with meningitis (adjusted odds ratio 11.7; 95% confidence interval [CI], 5.23-28.50). The AUROC of headache alone to predict meningitis was 0.65 (95% CI, 0.61-0.69), with 95% sensitivity and 35% specificity. The AUROC improved to 0.86 (95% CI, 0.82-0.90) when stiff neck, photophobia, confusion, sex, and CrAg titer ≥1:160 were added to the logistic regression model. In the final classification tree, headache combined with CrAg titer ≥1:160 demonstrated the highest probability (79%) of meningitis.

Conclusions: Headache and high CrAg titer is the most reliable predictor for meningitis. In the absence of plasma CrAg titration, symptoms of headache, stiff neck, photophobia, and confusion predict meningitis for individuals with cryptococcal antigenemia.