Clinical Infectious Diseases最新文献

Background: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States.

Methods: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model.

Results: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2).

Conclusions: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

Background: Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited.

Methods: We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999-2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model.

Results: Among 1,255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly S. aureus (49%; MSSA 37%, MRSA 13%). Over time from 1999-2004 to 2020-2024, Gram-negative bacilli increased from 6% to 14% (p=0.048).Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (sHR 1.92, 95% CI 1.18-3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17-2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37-0.87) and higher Charlson Comorbidity Index (CCI) (sHR 0.62, 95% CI 0.43-0.90) were associated with lower failure.

Conclusion: This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.

There is an unmet need for developing drugs for the treatment of gonorrhea due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug-resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On 23 April 2021, the US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institute of Allergy and Infectious Diseases of the National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of that workshop.

Background: Rates of drug-resistant tuberculosis (DR-TB) are increasing worldwide. Tuberculosis preventive treatment (TPT) for contacts of people with active TB is essential to halt infection progression and transmission. While newer TPT regimens for exposure to drug-susceptible and rifampin (R)-resistant strains (MDR-TB/RR-TB) are expanding, optimal treatment for contacts exposed to fluoroquinolone-resistant strains of TB (pre-XDR- or XDR-TB) remains unclear. In 2019-2020, Vladimir City, Russia, introduced moxifloxacin (Mfx)- and bedaquiline (Bdq)-based TPT regimens to prevent disease development in contacts exposed to MDR/RR-TB and pre-XDR-TB.

Methods: We conducted a retrospective cohort study of adult TB contacts, people experiencing homelessness, and people with HIV who received TPT in Vladimir between 2019 and 2020. Those without TB disease but with indications for TPT were offered 1 of 6 regimens, based on drug-susceptibility testing results of the index patient: rifapentine/isoniazid (3HP), isoniazid (6H), rifabutin/isoniazid (3HRb), 4R, 4Mfx, or 3Bdq. Adverse drug reactions (ADRs) were monitored with monthly lab tests and electrocardiogram (ECGs). Outcome measures included ADRs, TPT completion, and TB disease incidence during the 12-month follow-up period.

Results: Over 24 months, 403 people started TPT. No life-threatening ADRs or deaths occurred. The lowest ADR rate and highest completion were seen with 3Bdq (95.2%) compared to 3HP (75.9%, Mid-P exact = .03). Tuberculosis incidence per 1000 person-years was 4 times higher among eligible individuals who declined TPT versus those initiating it.

Conclusions: Preventive therapy for drug-resistant TB, including fluoroquinolone-resistant strains, is acceptable, safe, and effective. Implementation of comprehensive TPT programs in high-burden DR-TB settings can protect contacts and reduce transmission.