Open Forum Infectious Diseases最新文献

Background: Lenacapavir is a twice-yearly HIV-1 capsid inhibitor approved, in combination with other antiretrovirals, for the treatment of heavily treatment-experienced people with multidrug-resistant HIV, based on the Phase 2/3 CAPELLA study. Here, we report week 156 efficacy and safety results.

Methods: In CAPELLA (NCT04150068), participants received 2-week oral lenacapavir lead-in doses, followed by subcutaneous lenacapavir every 6 months, combined with an investigator-selected optimized background regimen. Endpoints included virologic outcomes, CD4 cell count trends, adverse events, and treatment-emergent resistance.

Results: CAPELLA enrolled 72 participants: 25% female; 38% Black; median age, 52 years; CD4 cell count <200 cells/μL, 64% (<50 cells/μL, 22%). At week 156, 61% (43/70) had HIV RNA <50 copies/mL by FDA Snapshot Algorithm, 16% (11/70) had ≥50 copies/mL, and 23% (16/70) had missing data; by missing = excluded analysis, 85% (44/52) had HIV RNA <50 copies/mL. Mean CD4 cell count increase from baseline to week 156 was 164 cells/μL (95% CI: 116-211). Through week 156, 14/72 participants developed emergent LEN resistance. Injection site reactions were mostly Grade 1/2, and frequency declined over time. Through week 156, two participants discontinued lenacapavir due to Grade 1 injection site nodules.

Conclusions: Lenacapavir plus an optimized background antiretroviral regimen maintained a high rate of virologic suppression at week 156 with continued increases in CD4 counts. Lenacapavir was well tolerated with a favorable safety profile and very low rates of lenacapavir discontinuation. These data demonstrate longer-term efficacy and safety of lenacapavir for heavily treatment-experienced people with multidrug-resistant HIV.

Multisystem inflammatory syndrome in children (MIS-C) is an emergent postinfectious hyperinflammatory disorder predominantly affecting the pediatric population following COVID-19 infection. Clinically, it is characterized by persistent fever, shock, multiorgan involvement, and potentially severe cardiovascular involvement. This comprehensive review synthesizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnostic criteria, with particular emphasis on the management of MIS-C. We also stress on the importance of distinguishing MIS-C from phenotypically similar entities. Acute-phase management centers on supportive care, hemodynamic stabilization, and targeted immunomodulation, with intravenous immunoglobulin, corticosteroids, and biologic forming the therapeutic cornerstone. Thromboprophylaxis is frequently warranted due to the elevated thromboembolic risk, and long-term follow-up is essential to monitor for cardiac, gastrointestinal, and neurologic complications. Additional considerations include postrecovery vaccination protocols and the use of extracorporeal membrane oxygenation in cases of refractory cardiorespiratory failure. Despite advancements in clinical outcomes, diagnostic ambiguity and heterogeneous management guidelines continue to pose significant challenges.

Hepatitis C virus treatment guidance was updated to include sustained virologic response at 4-weeks post-treatment (SVR4) as an alternative measure of cure for select groups. Among a community-based sample of people who inject drugs receiving an accelerated test-and-treat protocol, results at treatment completion and SVR4 predicted those at 12-week post-treatment.

[This corrects the article DOI: 10.1093/ofid/ofae583.].

Background: Adults hospitalized with respiratory syncytial virus (RSV) face mortality risks comparable to or higher than those with influenza A or B. However, studies on the impact of bacterial co-infections on mortality are inconsistent.

Methods: This multicenter cohort study included adults hospitalized with RSV, influenza A, or B over 3 years at two tertiary care hospitals. Microbiological testing, bacterial co-infections, antibiotic use, and their association with clinical outcomes were analyzed using adjusted linear and logistic regression models.

Results: Of 986 patients, 352 (36%) had RSV, 347 (35%) influenza A, and 287 (29%) influenza B. The median age was 74 years, 54% were women, and 76% had at least one comorbidity. Overall, 32% had pneumonia. The prevalence of bacterial co-infections was comparable across patients with RSV (23%), influenza A (25%), and B (28%). Among patients without bacterial co-infection, antibiotic use within 48 hours remained common across all virus groups (77%, 71%, and 75%, respectively). In adjusted analyses, bacterial co-infection in patients with RSV was not associated with mortality at 14, 30, or 90 days, high-flow oxygen therapy, mechanical ventilation, or length of stay (LOS). Early antibiotic treatment was associated with prolonged LOS but not improved survival.

Conclusions: Bacterial co-infections were identified in approximately one-quarter of patients with RSV, influenza A, and B. Among patients with RSV, bacterial co-infection was not associated with adverse clinical outcomes, and early antibiotic treatment did not appear to improve clinical outcomes.

Background: In the United States (US), people with human immunodeficiency virus (PWH) have an increased risk of myocardial infarction, including type 1 myocardial infarction (T1MI) and type 2 myocardial infarction (T2MI). Presentations and clinical trajectories of PWH experiencing acute myocardial injury (AMI) have not been well characterized.

Methods: Leveraging electronic health records (EHRs) from a US academic medical center, we identified PWH presenting to the emergency department from 2015 to 2019 with a troponin T ≥99th percentile. Presentations were adjudicated as AMI, T2MI, or T1MI. Clinical presentations, provider-level responses, and ensuing clinical outcomes (post-index event) were compared. Among PWH with AMI or T2MI, observed incidence of ensuing major adverse cardiovascular event (MACE) was evaluated using the cumulative incidence function by Aalen estimator. Adjusted cause-specific Cox proportional hazards models were used to assess the association between presentation type and ensuing MACE.

Results: Among 79 cases analyzed, presentations of AMI and T2MI were more common than T1MI (29.1% and 64.6% vs 6.3%, respectively). Infection represented the most common event trigger for AMI and T2MI. Among PWH presenting with AMI versus T2MI, there was no difference in risk of ensuing MACE (adjusted hazard ratio, 1.14 [95% confidence interval, .48-2.71]). The proportion of cases of AMI versus T2MI not categorized with any cardiovascular disease-related diagnosis code differed significantly (91% vs 53%, P = .001).

Conclusions: Among US PWH presenting for emergency care, AMI was infrequently coded in the EHR. AMI and T2MI were associated with comparable rates of ensuing MACE. Enhanced recognition/documentation of AMI among PWH will facilitate development of preventive care approaches.

Background: Longitudinal data are scarce on sepsis bundle adherence and associated survival at a country or regional level.

Methods: A population-based electronic health record database was leveraged to determine temporal trends in sepsis bundle adherence (empirical broad-spectrum antibiotic administration, blood culture collection, lactate measurement) on sepsis onset day and antimicrobial resistance (AMR) prevalence. This study included all adult hospitalizations for community-acquired sepsis at 41 publicly funded hospitals in Hong Kong between 2009 and 2018. Generalized estimating equations were used to assess the association between full bundle adherence and its individual elements with hospital mortality.

Results: Among 421 096 cases of community-acquired sepsis, the full bundle adherence rate increased from 0.2% in 2009 to 1.2% in 2018 (relative +18.9%/y, P < .001), with limited uptake of each element. The relative increase in empirical broad-spectrum antibiotics administration (+9.8%/y [95% CI, 8.3%-11.2%]) was faster than the AMR prevalence (+5.2%/y [95% CI, 3.6%-6.9%]). Full bundle adherence was associated with reduced mortality (adjusted odds ratio [OR_adj], 0.75 [95% CI, .65-.86]). Blood culture collection was associated with reduced mortality (OR_adj, 0.88 [95% CI, .83-.93]), while lactate measurement was associated only with reduced mortality in septic shock (OR_adj, 0.85 [95% CI, .76-.94]). Broad-spectrum antibiotics was associated with reduced mortality (OR_adj, 0.73 [95% CI, .56-.96]) when used appropriately in bacteremia from extended-spectrum beta-lactamase pathogens or methicillin-resistant Staphylococcus aureus.

Conclusions: Basic sepsis care implementation remains challenging even in high-income settings. Empirical broad-spectrum antibiotic usage has outpaced AMR risk. Full sepsis bundle adherence was associated with improved survival, but empirical broad-spectrum antibiotics was associated with better survival only if used appropriately. Efforts should focus not only on ensuring bundle adherence but also on prioritizing the right treatments for the right patients.

Candida krusei is diploid, dimorphic, opportunistic yeast belonging to the methylotrophic clade, known for causing infections primarily in immunocompromised individuals. It is globally distributed with variable prevalence across regions and patient populations. C krusei has been associated with several nosocomial outbreaks, particularly in neonatal intensive care units. A key concern is its intrinsic resistance to fluconazole, often resulting in high mortality. The mechanisms of azole resistance are complex and include low affinity of the Erg11p enzyme, overexpression of efflux pumps, and mutations in the ABC11 gene. Additionally, echinocandin resistance has emerged due to mutations in the hotspot regions of the FKS1 gene. Its biofilm-forming ability further enhances its survival against antifungal agents and immune responses. This study highlights C krusei as a clinically significant and emerging fungal pathogen, emphasizing the need for enhanced surveillance, molecular monitoring, and continued research to mitigate its growing threat in healthcare settings.

Although several antiviral agents are licensed for the treatment of orolabial and genital herpes simplex virus infections, new therapies are needed. Trial design is challenging for these indications due to the heterogeneity of endpoints in prior trials. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials published between 1995 and 2024 consisting of adults with established herpes simplex virus infection who were immunocompetent and nonpregnant. A total of 22 articles met the inclusion criteria. For episodic treatment, endpoints included time to healing, proportion with an aborted lesion, and time to cessation of symptoms. For daily suppressive therapy, endpoints included time to first recurrence, proportion recurrence-free at 1 year, and total shedding rate. We observed that over the last 30 years, clinical trials have used various endpoints with nonstandardized definitions. A reassessment of appropriate endpoints along with regulatory guidance would assist with consistent study design for evaluation of new agents.