Open Forum Infectious Diseases最新文献

Background: Vancomycin-resistant enterococci (VRE) bacteremia is associated with substantial mortality. Rapid molecular diagnostic testing (RMDT) that detects enterococci and vancomycin resistance genes from positive blood culture broths may lead to earlier appropriate antimicrobial therapy for VRE bacteremia, which could improve clinical outcomes.

Methods: We conducted a retrospective cohort study of patients with VRE bacteremia from 2010 to 2019. RMDT that detects enterococci and vancomycin resistance genes from positive blood cultures was implemented in October 2014. We compared time to active antimicrobial administration, mortality, and other outcomes in patients whose positive blood cultures underwent RMDT (postintervention) and those whose did not (preintervention).

Results: Of 577 eligible patients with VRE bacteremia, 237 (41.1%) had blood cultures that underwent RMDT. The RMDT cohort had shorter median time from culture collection until receipt of active antimicrobial therapy (21 vs 32 hours, P < .001) than the non-RMDT cohort. There was no difference in 30-day mortality (31.6% vs 36.5%, P = .230). A post hoc subgroup analysis excluding patients with leukemia (who received empiric VRE-active therapy based on Gram stain results) found that RMDT was associated with decreased 30-day mortality: 29.6% versus 40.8%, P = .037. On multivariate analysis, that improvement in 30-day mortality in patients without leukemia did not persist.

Conclusions: RMDT was associated with decreased time to receipt of active antimicrobial therapy in VRE bacteremia. There was no improvement in mortality associated with the use of RMDT. RMDT for VRE bacteremia may improve time to identification and treatment of VRE bacteremia but does not clearly improve clinical outcomes.

Background: Early identification of non-adherence to daily antiretroviral therapies may facilitate targeted transition to long-acting HIV regimens for individuals most likely to benefit. This study evaluated the feasibility of detecting emtricitabine (FTC) and tenofovir (TFV) in oral fluids to monitor daily oral pre-exposure prophylaxis (PrEP) adherence.

Methods: We collected 241 oral fluids from 22 HIV-negative adults randomized to 2, 4, or 7 doses/week of oral PrEP with FTC/TDF for directly observed therapy. Generalized Estimating Equations were used to examine the associations between FTC/TFV detectability and three dimensions of PrEP adherence: dosing recency, cumulative dosing time, and dosing frequency. We also assessed the diagnostic accuracy of FTC levels in oral fluids for predicting daily oral PrEP non-adherence (time since the last dose >24 hours).

Results: Among 165 oral fluids with a time since the last dose within 48 hours, 9.0% had detectable TFV, and 53.3% had detectable FTC. Compared with oral fluids collected within 24 hours since the last dose, those collected between 24 and 48 hours since the last dose had significantly lower odds of having detectable FTC (odds ratio: 0.21, 95% confidence interval [CI]: 0.11-0.38). An FTC threshold of <7.5 ng/mL achieved a sensitivity of 90% (95% CI: 84%-94%) and a specificity of 65% (95% CI: 57%-74%) for identifying recent PrEP non-adherence.

Conclusions: FTC can be detected in oral fluids and may be a promising pharmacologic marker for identifying recent PrEP non-adherence as early as one dose missed. TFV had lower concentrations in oral fluids, and is not suitable for adherence monitoring. Clinical Trials Registration. NCT0301260.

Introduction: Fidaxomicin is a narrow-spectrum, nonabsorbable antibiotic recommended as first-line therapy for nonfulminant Clostridioides difficile infection (CDI). While some studies suggest a reduction of recurrence for immunocompromised hosts (ICHs), the findings remain inconsistent and limited. We aimed to evaluate the clinical outcomes of fidaxomicin for a first CDI episode in ICHs within a large healthcare system.

Methods: We conducted a retrospective cohort study of Clalit Health Services adults with a first laboratory-confirmed CDI between January 2013 and December 2023. Patients with prior CDI were excluded. The primary outcome was a composite of recurrence, 90-day mortality, and colectomy, which were compared between the fidaxomicin and vancomycin groups. Secondary outcomes included each component individually.

Results: The study included 11 204 patients with a first CDI episode, of whom 2362 were immunocompromised. The fidaxomicin group had a significantly lower recurrence rate compared to vancomycin (8% vs 17%, P = .019), while it was not associated with reduced composite outcome (aOR = .65, 95% CI .39-1.07, P = .09). Multivariable analysis also confirmed a reduction in recurrence risk (aOR 0.44, 95% CI .21-.96). Older age, previous antibiotic use within 90 days, and hypoalbuminemia were independently associated with worse outcomes, while recurrence was linked to increased long-term mortality.

Conclusions: ICHs treated with fidaxomicin had significantly lower recurrence rates and fewer complications compared to vancomycin. Despite assumptions, ICHs had recurrence rates similar to immunocompetent patients, highlighting the role of comorbidities and treatment choices. Our findings support fidaxomicin as a preferred first-line option in select ICHs and underscore the need for individualized management strategies to improve outcomes in this high-risk population.

Background: Diagnosing meningitis and encephalitis remains challenging due to nonspecific clinical presentations and the limitations of traditional microbiological methods. Metagenomic next-generation sequencing (mNGS) offers a broad approach to detect pathogens, but its real-world impact on clinical decision-making remains undefined.

Methods: We used a cohort of patients with confirmed central nervous system infections and autoimmune encephalitis (AE) who underwent traditional microbiological cerebrospinal fluid testing at Columbia University Irving Medical Center. Using published sensitivity and specificity data for mNGS, we applied Bayes' theorem to calculate different etiology-specific pretest probabilities and model the potential impact in the diagnostic workflows including the number of lumbar punctures (LPs), additional etiologic tests potentially avoided, and time to diagnosis.

Results: The cohort includes 54 patients in the infectious cohort and 29 patients with confirmed autoimmune encephalitis. In a modeled scenario, utilizing an mNGS test, such as Delve Detect, in patients with DNA viral infections (n = 23) could lead to a reduction of up to 88 microbiological tests, 145 days to diagnosis, and 2 LPs in total. For bacterial infections (n = 16), estimated impact included a reduction of 30 microbiological tests, 144 days to diagnosis, and 12 LPs (Table 1). Although fungal, RNA viral and parasitic infections were less common, with adjusted positive predictive values of 92.8%, 89.5%, and 84.6%, respectively. In the autoimmune cohort, a total of 2 LPs, 126 microbiological tests, and 297 days to diagnosis could have been avoided through the use of mNGS.

Conclusions: Our analysis suggests that an mNGS test, such as Delve Detect, could potentially streamline diagnostic and treatment pathways in meningitis and encephalitis of infectious or autoimmune origin.

Background: People with HIV (PWH) are at higher risk of developing chronic hepatitis B, and therefore vaccination against HBV is highly recommended. Clearance of hepatitis B surface antibody (anti-HBs) over time is poorly described in PWH.

Methods: We retrospectively included vaccinated PWH with anti-HBs ≥10 IU/L from the French Dat'AIDS database. Those with a cured hepatitis B were excluded. For each participant, all anti-HBs levels were collected until March 2024. Anti-HBs peak was defined as the highest anti-HBs value and corresponded to entry into the analysis. Factors associated with anti-HBs clearance below 10 IU/L were identified using a multivariable Cox model.

Results: 11 082 PWH were included, 4480 had peak anti-HBs levels between 10 and 99 IU/L, 3268 between 100 and 499 IU/L, 1205 between 500 and 999 IU/L, and 2129 ≥ 1000 IU/L. Median follow-up was 3.8 [1.6, 7.1] years. Antibody clearance over time was similar in the three groups with peak anti-HBs ≥100 IU/L, and significantly slower than in the group with anti-HBs <100 IU/L. Peak anti-HBs level was the variable with the greatest impact on anti-HBs clearance in the multivariable analysis. Compared with participants with anti-HBs <100 IU/L, having peak anti-HBs values of 100-499 IU/L, 500-999 IU/L and ≥1000 IU/L were protective factors for anti-HBs clearance, with hazard ratios of .26 [0.23, 0.30], 0.17 [0.13, 0.22] and 0.10 [0.07, 0.12], respectively, P < .001.

Conclusions: Peak anti-HBs level is the key factor of antibody persistence in PWH. Those with anti-HBs levels below 100 IU/L should be monitored closely and considered for a booster dose.

A 65-year-old resident of Westchester County, New York was diagnosed with Plasmodium falciparum infection on 2 October 2023. The case had no recent history of international travel to a malaria-endemic area. An extensive epidemiological investigation was initiated to identify the most likely source of the infection and assess the risk of continuing local transmission. Interviews with the case identified multiple potential exposure routes including domestic travel within the United States, hospitalizations overlapping that of individuals diagnosed with travel-associated malaria, residential proximity to imported malaria cases, and outdoor activity overlapping the potential dusk/dawn biting activity of Anopheles mosquitoes. The epidemiologic investigation included syndromic surveillance, healthcare facility investigations, and genetic analysis of specimens collected from the case patient and other malarious patients with epidemiologic links. Results of the genetic analysis and epidemiologic investigation implicated blood-borne transmission in a healthcare setting from a concurrently hospitalized traveler with confirmed malaria. The mechanism remains unknown, although it was likely due to a lapse in infection control. No mosquito-transmitted cases were identified in New York. No additional induced cases from a blood-borne/healthcare-associated exposure were identified. The identification and prompt investigation of potentially locally acquired malaria infections can aid in preventing additional cases by identifying the source and enacting appropriate control measures if necessary.

Background: Tuberculosis remains the leading cause of death by a single infectious agent globally, with Ethiopia among the highest tuberculosis- and human immunodeficiency virus/tuberculosis-burden countries. Diagnostic gaps-particularly among household contacts (HHCs) unable to expectorate-hinder early case detection. Computer-aided detection software for chest radiography and nonrespiratory molecular assays, such as stool-based Xpert MTB/RIF testing, represent promising strategies for scalable screening.

Methods: We conducted a prospective diagnostic accuracy study at St Luke Catholic Hospital, Oromia, Ethiopia, enrolling 478 participants (152 tuberculosis index patients and 326 HHCs). All HHCs ≥4 years underwent digital chest radiographic screening, with or without CAD4TB (Delft Imaging) software assistance, and provided stool and sputum samples for Xpert MTB/RIF testing. The accuracy of CAD4TB and stool Xpert testing was evaluated against sputum Xpert testing as the reference.

Results: CAD4TB showed strong diagnostic performance, with a sensitivity of 0.77 (95% confidence interval, .70-.83) and specificity of 0.93 (.90-.96). Performance was higher among adults (sensitivity and specificity, 0.79 and 0.94) than in children (0.64 and 0.92). Stool and sputum Xpert testing demonstrated high concordance (Cohen's κ = 0.76), with a sensitivity of 0.77 (95% confidence interval, .70-.84) and specificity of 0.97 (.93-.99). During the study, 10.6% of HHCs (34 of 321) were newly diagnosed microbiologically with tuberculosis.

Conclusions: The combined use of CAD4TB and stool Xpert testing significantly improves tuberculosis detection, particularly among HHCs in high-burden, low-resource settings. This strategy is especially valuable in children and adults unable to produce sputum and where radiological expertise is limited.

Background: Previous research suggests the COVID-19 pandemic was associated with reductions in HBV testing early in the pandemic. However, impacts of the pandemic on HBV testing in the longer-term and among people who inject drugs (PWID) are unclear. We investigated the impact of the pandemic and related policies on HBV testing from 2020 to 2022, including among PWID, in British Columbia (BC), Canada.

Methods: Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses of HBV surface antigen (HBsAg), HBV DNA, and HBV e-antigen (HBeAg) testing. The study included a prepandemic period (January 2017-February 2020), a transition period (March-May 2020), and pandemic periods in 2020 (June-December), 2021, and 2022.

Results: HBsAg testing decreased by 16.5% (95% CI 13.9-18.9) and HBV DNA testing decreased by 11.6% (95% CI 9.5-13.6) in June-December 2020 relative to predicted levels, and testing remained lower than predicted throughout 2021 and 2022. Percentage reductions in HBV DNA testing were greater for PWID compared with non-PWID in 2020 (30.0% vs 11.2%) and thereafter. Changes in HBeAg testing overall were less pronounced but varied by sex and age.

Conclusions: The pandemic and related policies were associated with decreases in HBsAg and HBV DNA testing in 2020, and testing remained lower than predicted throughout 2021 and 2022. Additional efforts to increase HBV testing are needed, including strategies to ensure linkage to care for PWID.

Background: Adult-onset immunodeficiency (AOID) due to anti-interferon-gamma autoantibodies (AIGA) predisposes patients to multiple opportunistic infections (OIs), including cutaneous involvement. However, data specifically addressing cutaneous OIs in AOID remain limited. This study aimed to characterize and compare clinical and laboratory features, with a focus on cutaneous OIs caused by mycobacteria and fungi.

Methods: A retrospective chart review was conducted on AOID patients with cutaneous OIs in Chiang Mai and Khon Kaen University Hospital from January 2000 to December 2020. Cases with infection due to Mycobacterium species-both Mycobacterium tuberculosis complex and non-tuberculous mycobacteria-and fungal pathogens were included. Clinical characteristics and laboratory parameters were analyzed, and a multivariate predictive model was developed to differentiate between cutaneous mycobacterial and fungal infections.

Results: A total of 61 AOID patients with 70 cutaneous infectious episodes were identified. Among these, fifty episodes were due to Mycobacterium infection. Lesions involving the neck with concurrent lymphadenopathy were more suggestive of Mycobacterium infection. In contrast, fungal infections were associated with generalized or truncal involvement, anemia, neutrophilia, lower monocyte percentage, hyperglobulinemia, and higher levels of aspartate aminotransferase. A multivariate model incorporating these variables achieved excellent discriminatory performance (area under the receiver operating characteristic curve: 0.94; 95% confidence interval: 0.87-0.99).

Conclusions: Cutaneous lesions involving the neck area and lymphadenopathy are clinical clues that suggest cutaneous Mycobacterium OIs. Nevertheless, integration of clinical features with laboratory findings enables the development of a predictive model that can effectively differentiate between cutaneous mycobacterial and fungal infections. This predictive model may aid in selecting appropriate empirical antimicrobial therapy, particularly when microbiological confirmation is pending or inconclusive despite high clinical suspicion.