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 [ORadj], 0.75 [95% CI, .65-.86]). Blood culture collection was associated with reduced mortality (ORadj, 0.88 [95% CI, .83-.93]), while lactate measurement was associated only with reduced mortality in septic shock (ORadj, 0.85 [95% CI, .76-.94]). Broad-spectrum antibiotics was associated with reduced mortality (ORadj, 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.
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.
Background: We aimed to identify and evaluate clinical subphenotypes in a cohort of patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) and to assess their association with all-cause 90-day mortality.
Methods: This post hoc analysis of the MRSA-GEIRAS-SEIMC study was conducted across 15 Spanish hospitals. MRSAB in adult patients from 2019 to 2022 were included. Clinical subphenotypes were identified using a combination of principal component analysis and latent class analysis based on age, sex, comorbidities, SOFA score, creatinine levels, metastatic foci, source, and acquisition. The 90-day mortality associated with each subphenotype was estimated using the Kaplan-Meier method. Cox regression was performed to assess the risk of death.
Results: A total of 419 MRSAB were included. Four distinct subphenotypes were identified: S1 was associated with younger age, community acquisition, and unknown or skin and soft-tissue infection source; S2 was associated with older age, female sex, high burden of comorbidities, and healthcare-related acquisition; S3 was linked to a catheter source and nosocomial acquisition; and S4 was predominantly associated with the presence of heart valve prostheses, and metastatic foci. Significant differences in all-cause 90-day mortality were observed across subphenotypes: 20.0% in S1, 47.4% in S2, 26.2% in S3, and 35.1% in S4 (P < .01). Cox regression indicated an increased 90-day mortality risk in S2 (HR, 2.98; 95% CI, 1.59-5.56) and S4 (HR, 1.99; 95% CI, 1.16-3.42) compared with S1.
Conclusions: We identified 4 distinct clinical subphenotypes of MRSAB associated with prognostic outcomes. Further investigation is needed to implement them into clinical practice.
Background: Despite classification as the most common endemic mycosis in the United States, few data exist supporting the optimal care of patients with histoplasmosis, making diagnosis and treatment challenging. This study aimed to describe patients with histoplasmosis across a Michigan health system.
Methods: A retrospective, multicenter cohort study of patients diagnosed with histoplasmosis between January 2020 and April 2023. The primary objective was to describe patients diagnosed with histoplasmosis, methods of diagnosis, and treatment they received. Patient outcomes, including mortality with treatment, and 6-month relapse of disease, were also evaluated.
Results: A total of 88 patients were included in the study, and most received care from an infectious diseases provider (86.4%). Tissue histopathology was the most common diagnostic method (59%). Treatment was initiated in 58 patients (66%); 17 (29.3) had disseminated disease. Five (8.6%) patients died within 6 months. Itraconazole was the agent most prescribed for definitive therapy (81%) followed by posaconazole (17%). Median treatment duration was 24 weeks. Adverse events occurred in more than one quarter of patients receiving triazoles. Loading doses were absent in 35% of itraconazole prescriptions; therapeutic drug monitoring was absent in 19.2%. No patients experienced a relapse of disease within 6 months of therapy completion.
Conclusions: In a cohort of patients with histoplasmosis from Michigan, variation in diagnostic testing and treatment was observed. Most patients were diagnosed by positive tissue histopathology and itraconazole was the most frequently prescribed antifungal followed by posaconazole. Opportunities for more sensitive diagnostic testing and improved antifungal dose optimization and monitoring were identified.
Background: Since September 2022, an ongoing increase in gonorrhea positivity rates and diagnoses among young women visiting sexual health centers was observed in the Netherlands. To gain more insight into possible drivers of this increase, this study aimed to investigate the molecular diversity, clustering, and transmission of Neisseria gonorrhoeae related to the gonorrhea increase in the Netherlands.
Methods: Between January 2022 and March 2023, viable and stored N gonorrhoeae isolates from vaginal swab samples from 273 women <25 years of age were included from 4 sexual health centers in the Netherlands. All isolates were subjected to whole genome sequencing. The molecular diversity was investigated by analyzing (core genome) multilocus sequence types (STs) over time and by patient characteristics.
Results: The prevalence of ST7359 and ST7822 increased from <5% in the beginning of 2022 to ∼23% in 2023 and ST9363 from 6% to 14%. ST7359 and ST9363 were associated with hosts with university-level education and Dutch ethnicity. ST7359 and ST7822 also included large clusters of genetically related isolates (<6-gene difference). No indication for reduced antimicrobial susceptibility to ceftriaxone was found in any ST.
Conclusions: The N gonorrhoeae surge among young women is not caused by a single strain. The prevalence of STs shifted over time, and certain STs were associated with distinct populations and showed clustering of genetically related isolates. These findings suggest rapid clonal expansion of several circulating STs. This may be indicative of increased transmission within specific sexual networks.
Infectious diseases telehealth (IDt) management of outpatient parenteral antimicrobial therapy (OPAT) across 18 small community hospitals was associated with similar rates of OPAT failure, lower rates of clinical failure and mortality, and higher likelihood of inpatient source control procedure compared to OPAT managed by other services. IDt program expansion might further improve care.
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