Open Forum Infectious Diseases最新文献

Background: Outcomes of patients with acute pyelonephritis (AP) treated in a hospital-at-home setting have not been comprehensively evaluated in the United States.

Methods: We performed a multicenter, retrospective cohort study of adults diagnosed with and managed for AP in Mayo Clinic's Advanced Care at Home (ACH) program between July 2020 and January 2025. Collected data included demographics, Charlson Comorbidity Index (CCI), genitourinary comorbidities, severity of illness (SOI), and risk of mortality (ROM) scores, as well as pyelonephritis-related complications. Outcomes included length of stay (LOS), escalation of care, and 30-day postdischarge emergency department (ED) visits, readmissions, and mortality.

Results: A total of 165 patients met inclusion criteria. Median age was 67 years; SOI scores were moderate in 33.3%, major in 52.1%, and extreme in 8.5%. ROM scores were moderate in 30.3%, major in 38.2%, and extreme in 6.7%. Median CCI score was 5, and all patients had preexisting genitourinary conditions. On admission, 30.9% met sepsis criteria, acute kidney injury was present in 47.3%, and bacteremia developed in 33.3%. Median LOS in the ACH program was 3.1 days. Only 4.8% required escalation to a brick-and-mortar hospital. Readmission occurred in 17.0%, and 4.8% had ED visits. No in-program deaths occurred.

Conclusions: This multicenter retrospective study shows that AP, including cases with high illness severity and complex comorbidities, can be managed safely and effectively in a hospital-at-home setting with careful patient selection and robust infrastructure to support timely escalation when needed.

Vaccine effectiveness of BNT162b2 KP.2 vaccine against COVID-19 hospital admissions was 49% (95% CI, 30-63) and 45% (95% CI, 35-54) against emergency department/urgent care encounters (vs no KP.2 vaccine at <3 months). Protection persisted >90 days from vaccination with some waning. Vaccine effectiveness remained high regardless of prior COVID-19 vaccination and among older adults.

Background: In many resource-limited settings, hospitalization for community-acquired infection is common, but data regarding illness severity, etiology, and morbidity remain sparse.

Methods: We conducted a prospective observational study from May 2022 to August 2023 at 2 hospitals in northeast Thailand. Adults hospitalized with community-acquired infection were enrolled within 24 hours of admission and followed up to 28 days. We identified patients meeting sepsis criteria and assessed related epidemiology, management, and mortality risk factors.

Results: Of 1445 patients screened, 940 were enrolled. The median age was 60 years and preexisting diabetes mellitus was common (42%). Sixty-six percent of patients met sepsis criteria. Blood cultures and broad-spectrum antibiotics on admission were common (both >95%), although lactate measurement was performed in 43% of patients with sepsis. In patients with sepsis, critical illness outside the intensive care unit was common on medical ward admission, including respiratory failure (33%) and shock (21%). Tropical etiologies of infection included melioidosis (8%) and leptospirosis (4%), and gram-negative organisms accounted for 81% of bacteremia. Twenty percent of patients with sepsis died by 28 days. Sepsis-associated acute kidney injury (SA-AKI) on admission was independently associated with mortality (adjusted odds ratio, 2.07; 95% CI, 1.30-3.29; P = .002), and patients with SA-AKI had worse survival (P < .001) than those without.

Conclusions: In rural Southeast Asia, sepsis is common among patients hospitalized with infection and associated with substantial morbidity and mortality. Distinct pathogens and broad-spectrum antibiotics are common, even in the absence of sepsis. We identified several modifiable risk factors of death, including SA-AKI, potentially influencing initial management in similar settings.

Background: Bedaquiline, pretomanid, and linezolid with or without moxifloxacin (BPaL/M) are recommended oral 6-month treatment regimens for multidrug- or rifampin-resistant (MDR/RR) tuberculosis (TB). Since the US rollout of these regimens in 2019, the US Centers for Disease Control and Prevention (CDC) and partners have identified patients who failed or relapsed on these regimens.

Methods: Here, we report a case series of US patients with TB treated with BPaL/M-containing regimens, who experienced adverse outcomes during the period 2022‒2024, including drug resistance, relapse, and treatment failure.

Results: Clinical and public health outcomes were significant for US patients reported. There were 8 patients identified (n = 8). 5 (62.5%) were male, with a median age 57 years, 2 (25%) were previously treated for TB, and 8 (100%) presented with cavitary disease. This included a patient who died from infectious TB with acquired resistance after exposing over 100 healthcare workers, a waitress who was found to have highly infectious TB at the time of her relapse, and a son who contracted Mycobacterium tuberculosis (Mtb) with reduced activity to bedaquiline from his mother in a household transmission event.

Conclusions: These patients highlight consequences, both for the individual and public health, of relapse and treatment failure in real-life operational settings that may not be readily evident in well-controlled and well-resourced clinical trials. Despite the advent of shorter and better tolerated bedaquiline-based regimens, US clinicians continue to face challenges in managing drug-resistant TB. These data support the need for expert management of these patients beyond routine TB care, as well as the need for close monitoring and follow-up months after treatment completion.

Background: Multidrug-resistant gram-negative (MDR-GN) sepsis is a significant cause of neonatal mortality in low- and middle-income countries (LMICs). The role of vertical transmission in neonatal MDR-GN colonization and thereby invasive infection remains unknown. The aim of this study was to systematically review literature detailing the molecular relatedness of maternal and neonatal MDR-GN colonization isolates in LMICs, characterizing the extent of vertical transmission.

Methods: Following PRISMA guidelines, PubMed and Scopus databases were searched for LMIC literature reporting molecular evidence of MDR-GN concordance for mother-neonate dyads.

Results: Of 90 articles identified by the search, 11 met inclusion criteria. Findings demonstrated substantial MDR-GN colonization in dyads from LMICs, although with significant heterogeneity in sampling methods. From MDR-GN dyads, molecular methods rarely found relatedness. Many studies suggested horizontal transmission within the environment.

Conclusions: In LMICs, maternal MDR-GN colonization rarely results in vertical transmission to neonates. However, literature remains scarce and further research is needed.

Change in liver fibrosis was studied over 5 years after cure of hepatitis C (HCV) in participants with and without HIV from the Viral Hepatitis C Infection Long-Term Cohort Study (VHICS). Markers of liver fibrosis included aspartate aminotransferase to platelet ratio (APRI), fibrosis 4 index (FIB-4), and a direct measure of extracellular matrix, enhanced liver fibrosis (ELF). We evaluated 122 participants without HIV and 128 with HIV. At study entry, which occurred on average 30 weeks after antiviral completion, more participants had severe fibrosis by ELF (21%) than FIB-4 (7%) or APRI (1%). ELF scores were not available before entry into VHICS. The proportions of participants in predefined ELF categories were similar between the 2 groups at study entry and over time. Advanced fibrosis by ELF did not decrease over time. Clinical events were observed in 44 (12%): 29 HCV/HIV and 15 HCV participants. HCV/HIV participants had a 1.95 times higher risk of developing a clinical event, compared to HCV. A lower entry ELF score was numerically associated with a lower risk of a clinical event. There was an association between VHICS entry ELF and time to first targeted liver diagnosis or all-cause death (hazard ratio; 95% CI, 0.268 [.094-.763], P = .014). In conclusion, APRI and FIB-4 decreases occurred early after direct-acting antiretroviral therapy, likely from decreased necroinflammation. ELF identified participants who continued to have advanced liver fibrosis and was associated with development of liver outcomes and death. Studies after sustained virologic response should include longer term follow up to monitor for clinical events.

Background: Understanding the extent of cross-protection conferred by the historic smallpox vaccination and the immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) after the 2022 global mpox outbreak is essential to inform current prevention strategies. In this study, we assessed the seropositivity and neutralizing capacities of the vaccinia virus (VACV)- and monkeypox virus (MPXV)-specific antibodies in 260 Taiwanese individuals.

Methods: We analyzed serum samples from 260 individuals in Taiwan, stratified by their birth year, before or after 1979, the year of smallpox vaccination cessation. ELISA and plaque reduction neutralization tests were conducted to assess VACV- and MPXV-specific antibody responses. Furthermore, we evaluated an additional cohort of MVA-BN vaccines (n = 9) before and after vaccination.

Results: Over 80% of individuals born before 1979 retained VACV-reactive antibodies, with 84% of this seropositive subgroup exhibiting neutralizing activity. We detected cross-reactive MPXV antibodies in 69% of individuals who were VACV-seropositive; however, only 65% had MPXV-neutralizing capacity, with titers significantly lower than those against VACV. MVA-BN vaccination enhanced VACV and MPXV antibody levels; however, MPXV-neutralizing titers remained low, particularly in individuals without prior smallpox immunization.

Conclusions: Historical smallpox vaccination induces long-lasting humoral immunity, and a correlation between VACV and MPXV antibody levels further suggests that it provides some degree of cross-protection against MPXV infection. MVA-BN boosted orthopoxvirus immunity; however, it may be limited in MPXV neutralization in vaccine-naïve populations. These findings offer useful insights for future mpox vaccination strategies and public health planning in regions with varying smallpox vaccination histories.

Background: Emerging evidence suggests that human cytomegalovirus (HCMV) infection is associated with tuberculosis (TB) disease. This study aimed to assess the relationship between the dynamics of HCMV markers and TB disease in people with human immunodeficiency virus (PWH).

Methods: In a case-control study nested within a Thai HIV cohort, stored samples from people with HIV who were diagnosed with TB disease after antiretroviral therapy (ART) (cases) and TB-negative controls matched 1:2 on ART duration. HCMV DNA, immunoglobulin M (IgM), and immunoglobulin G (IgG) were measured at 3 timepoints: (i) 6-24 months before TB diagnosis (pre-TB visit), (ii) at TB diagnosis (TB visit), and (iii) 6-24 months after TB diagnosis (post-TB visit).

Results: We enrolled 34 TB cases and 68 controls, the majority of whom were male (56% vs 60%). At the pre-TB visit, all participants were IgG seropositive, and there were no significant differences in the proportion with HCMV viremia or in HCMV IgM or IgG levels. At the TB diagnosis visit, the proportion of HCMV viremia was higher among TB cases compared with controls (34.5% vs 13.8%; P = .028). HCMV IgM geometric mean concentration (GMC) was higher in cases (0.17 vs 0.12 AU/mL; geometric mean ratio, 1.38 [95% confidence interval, 1.01-1.87]; P = .039). At the post-TB visit, HCMV viremia remained more frequent in cases (31.8% vs 4.5%; P = .006).

Conclusions: HCMV viremia and serology measured 6-24 months before TB diagnosis in cases did not differ from those in matched controls. At TB diagnosis, people with HIV with TB had higher proportion of HCMV viremia and higher GMC of HCMV IgM, possibly reflecting HCMV reactivation due to TB disease.

Background: Data on clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) in resource-limited, high tuberculosis (TB) burden settings, especially in Brazil, remain scarce.

Methods: This multicenter retrospective study evaluated all CPA cases diagnosed between 2012 and 2018 across eight centers in Brazil, examining clinical presentation, diagnosis, treatment, mortality, and factors associated with death, including differences related to pulmonary TB. To identify independent predictors of mortality, we conducted multivariate Cox regression. One-year mortality was analyzed using Kaplan-Meier survival curves.

Results: A total of 191 CPA cases were diagnosed, with a median age of 50 years (IQR 40-59) and 62% were male. TB was the most frequent predisposing condition (n = 138, 72%). Most patients (80%) received antifungal therapy, primarily itraconazole (n = 140, 73%). Surgery was performed in 34% of cases. According to Kaplan-Meier analysis, the cumulative mortality at 12 months was 6%. Compared to survivors, nonsurvivors had significantly lower rates of TB (52% vs 77%, P = .019) and higher rates of malignancies (13% vs 3%, P = .033). In multivariate analysis, only TB was independently associated with lower mortality (HR 0.413, 95% CI: .179-.954, P = .038). The TB group showed more hemoptysis (P = .008) and greater radiological involvement, suggesting delayed diagnosis.

Conclusions: In Brazil, the mortality of CPA was lower compared with that reported in previous studies, particularly among patients with TB. In TB-endemic, resource-limited settings, overlapping clinical and radiological features may delay diagnosis and antifungal treatment.

Background: Nocardiosis primarily affects immunocompromised hosts and those with chronic pulmonary disease but can also occur in immunocompetent patients. Predictors of dissemination and its role in long-term mortality remain unclear.

Methods: We conducted a retrospective cohort study of adults with nocardiosis diagnosed from January 1, 2010 to December 31, 2023. Patients were categorized into 3 groups: immunocompromised, immunocompetent with chronic lung disease, and immunocompetent without chronic lung disease. We evaluated risk factors associated with dissemination at the time of diagnosis and predictors of 1-year mortality. Multivariable logistic regression identified risk factors for dissemination. Cox regression assessed predictors of 1-year mortality.

Results: Among 232 patients, 44 (19.0%) had disseminated infection and 36 (15.5%) died within 1-year. Dissemination was more common among patients who were immunocompromised (odds ratio ([OR] 6.26, 95% confidence interval [CI] 2.26-20.53) or immunocompetent without chronic lung disease (OR 5.09, 95% CI 1.75-17.15). Lymphopenia and infection with Nocardia farcinica were also independently associated with dissemination. Dissemination was not associated with mortality overall (hazard ratio [HR] 1.58, P = .222), though interaction analysis revealed that dissemination was significantly associated with 1-year mortality only in immunocompetent patients with chronic lung disease (HR 9.43, 95% CI 1.73-51.52).

Conclusions: Immunocompromised patients and those without chronic lung disease are at increased risk for disseminated nocardiosis. While dissemination alone is not predictive of 1-year mortality overall, it is directly associated with mortality among immunocompetent patients with chronic lung disease. These findings highlight the need for tailored prognostic assessment and management in this subgroup.