Clinical Infectious Diseases最新文献

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.

Background: Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with long-term cognitive impairment in children, but little is known about cognitive impairment in children with other forms of severe malaria.

Methods: In this prospective cohort study of 600 Ugandan children 6 months to 4 years of age with 1 or more of the 5 most common forms of severe malaria (CM, respiratory distress, malaria with multiple seizures, SMA, or prostration), overall cognitive ability, attention, and associative memory were evaluated 12 months after hospital discharge. Age-adjusted z-scores for each domain were calculated from the scores of community children (CC) with no acute illness. Groups were compared using linear regression adjusted for potential confounding factors.

Results: Children with CM or SMA had significantly lower overall cognition scores than CC (mean difference [95% CI]: CM -0.66 [-1.12, -0.21], P = .001, SMA -0.71 [-1.05, -0.37], P < .001), and a greater proportion of children with CM (5/47, 10.6%) or SMA (17/140, 12.1%) had cognitive impairment (z-score < -2) than CC (2/104, 1.9%, P = .003 and 0.018, respectively). Cognition scores did not differ significantly between children with respiratory distress, multiple seizures or prostration and CC. Attention and associative memory scores did not differ significantly between children with any form of severe malaria and CC.

Conclusions: CM and SMA, but not other forms of severe malaria, are associated with long-term cognitive impairment in children <5 years of age.