Thomas Benfield

Staphylococcus aureus bacteremia (SAB) is associated with acute kidney injury (AKI). Recent reports have suggested that isoxazolyl penicillins are associated with AKI. To further investigate the relationship between antibiotic treatment and risk of AKI in patients with SAB, we studied a cohort of adults with methicillin‐susceptible SAB. AKI was defined using modified KDIGO criteria. Time‐dependent associations between antibiotic exposure and AKI were evaluated using landmark analyses combined with Fine–Gray competing risk models, treating death and hospital discharge as competing events. Absolute risks were estimated using the parametric g‐formula. Of the 1867 cases, 466 (25.0%) developed AKI within 14 days of blood culture. Accounting for time‐varying antibiotic exposure and competing risks, dicloxacillin, but not penicillin and cefuroxime, was associated with an increased rate of AKI at later landmarks within Days 1–5, with a higher rate observed on Day 5 (sHR: 4.84, 95% CI: 1.58–14.79). Absolute risk estimates were similar early after infection but diverged at later time points. In patients with SAB, AKI was common and occurred predominantly within the first 5 days. When accounting for time‐varying antibiotic exposure and competing risks, dicloxacillin was associated with an increased rate of AKI at later landmarks.

Background: Prior to the COVID‐19 pandemic, antiretroviral therapy (ART) coverage and viral suppression were improving across Europe; however, the impact of the pandemic on HIV care remains uncertain. Methods: In‐person visits, ART coverage and viral suppression among those on ART were described in the EuroSIDA cohort for each calendar year from 2016 to 2022 and compared across five European regions. Multivariable logistic regression was used to assess factors associated with having an in‐person visit and with viral suppression. Results: Among 6740 participants, 71.9% were men, 34.9% were MSM, and the median age was 50 years (IQR: 42–56) at baseline (2016). The proportion of in‐person visits dropped from 75.0% in 2019 to 67.8% in 2020, increased to 74.5% in 2021 and was 72.3% in 2022. We observed a consistent increase in ART uptake over the years and a slight increase in missing HIV‐RNA data in 2020. The odds of attending clinic in person were lower in 2020 compared with 2016 (aOR: 0.81, 95% CI 0.75–0.87) but not in 2021 or 2022, while viral suppression increased over calendar time ( p < 0.0001). Compared to Central‐Western Europe, the other regions had lower odds of in‐person visits ( p < 0.0001, most prominently for Southern Europe, aOR: 0.18) and viral suppression ( p < 0.0001, most prominently for Eastern Europe, aOR: 0.07). Conclusions: Our study confirmed the resilience of HIV care across Europe during the COVID‐19 pandemic, whereas the regional and country differences in clinic attendance and viral suppression highlighted the need to address persisting gaps in HIV care on a national level.

Background: Biologic drugs have substantially expanded treatment options for inflammatory bowel disease (IBD), but infection risk during exposure remains a concern. Aims: To investigate the association between current use of tumour necrosis factor‐α inhibitors (TNFi), vedolizumab and ustekinumab and bloodstream infection (BSI) in individuals with IBD. Methods: Nationwide, registry‐based case‐control study including all individuals with a first‐time microbiologically confirmed BSI from 2010 to 2024 and an IBD diagnosis (cases). Each case was matched with five controls with IBD using risk‐set sampling. Current biologic use was defined as recorded use of either TNFi, vedolizumab or ustekinumab within 180 days before the index date. Adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results: We included 4503 cases and 22,473 controls. TNFi use was associated with higher BSI rates compared with no current biologic use (aIRR 1.73, 95% CI 1.49–2.00), whereas vedolizumab (aIRR 0.85, 95% CI 0.61–1.20) and ustekinumab (aIRR 0.68, 95% CI 0.38–1.23) use was not. In pathogen‐specific analyses, TNFi use was associated with higher rates of BSI caused by Escherichia coli and Staphylococcus aureus , while vedolizumab use was associated with higher rates of Enterococcus faecium BSI. Concomitant glucocorticoid use was associated with increased BSI rates among TNFi and vedolizumab users compared with monotherapy. Conclusions: TNFi use was associated with increased BSI rates in patients with IBD, whereas vedolizumab and ustekinumab use was not. Overall, the findings suggest potential differences in infection risk across biologic therapies and in pathogen‐specific susceptibility.

Background: The burden of pneumococcal disease in older adults remains high in the postpneumococcal conjugate vaccine (PCV) era. We hypothesized that older adults may represent a carriage reservoir of Streptococcus pneumoniae. Methods: Paired naso- and oropharyngeal (NP and OP) swabs and questionnaires were collected during 2019–2022 from adults ≥65 years of age. Pneumococcal carriage and serotype distribution were determined by phenotypical and molecular methods. Results: A total of 172/1764 participants (9.8% [95% confidence interval {CI} 8.4–11.2]) were positive for carriage of S. pneumoniae by either culture (0.3%) or lytA/piaB DNA in NP (2.0%) or OP (8.4%) samples. Overall, 118 serogroup- or serotype-specific carriage events were identified by multiplex polymerase chain reaction across 16 distinct serospecificities in 93 samples, while 79 samples were nontypeable. PCV13 types accounted for 8.0%, nonvaccine types for 11.0% and polysaccharide pneumococcal vaccine 23 (PPV23)/non-PCV13 types for 81.0%. All carriage serotypes, except serotype 2, had been identified in invasive pneumococcal disease (IPD) isolates among adults ≥65 years during 2019–2022. Having young grandchildren was associated with increased odds of carriage (adjusted odds ratio [OR] 1.8, 95% CI 1.2–2.5, P = .0031). No association between PPV23 immunization and carriage was observed (OR 0.8, 95% CI .5–1.3). Conclusions: Older adults were carriers of a wide range of IPD-causing serotypes. Both carriage and IPD serotypes were mainly comprised of non-PCV13 serotypes. Immunization with higher valency conjugated vaccines is likely required to reduce residual pneumococcal disease among older adults.

Background: Influenza and SARS-CoV-2 can cause severe respiratory failure, but the metabolic pathways that lead to clinical deterioration are not fully uncovered. Tryptophan catabolism has been linked to disease progression and adverse outcomes. We aimed to find out whether the link between tryptophan catabolism and disease progression is shared by the 2 viral infections and, in an exploratory manner, to assess other metabolic pathways. Methods: Adults hospitalized due to influenza or SARS-CoV-2 from 3 prospective studies were pooled in a nested case-control study design. Cases were defined by disease progression: an increase in oxygen supplementation, intensive care unit admission, or death within 28 days. Cases were matched 1:2 to nonprogressors by pathogen and initial disease severity. We tested associations of plasma kynurenine, tryptophan, and the kynurenine/tryptophan ratio with disease progression. Metabolic profiles were investigated by unsupervised clustering-based, pathway-resolved methods. Results: We included 303 patients hospitalized with influenza or SARS-CoV-2. Higher levels of kynurenine and higher kynurenine/tryptophan ratios were associated with disease progression (odds ratio per log2 increase [95% CI], 1.81 [1.21–2.70] and 1.89 [1.26–2.84], respectively) independent of pathogen. Two metabolite modules were associated with disease progression. One module contained multiple amino acids, including kynurenine and 10 other tryptophan catabolism metabolites. The other module contained mainly lipids and xenobiotics. Conclusions: Several groups of metabolites were associated with disease progression independent of the pathogen. This indicates that biological mechanisms related to disease severity are shared in influenza and COVID-19. These mechanisms could be used for risk stratification of patients for potential disease-modifying treatments.

High systolic inter-arm blood pressure difference (SIABPD) is associated with cardiovascular events. We evaluated the prevalence of high SIABPD and its association with coronary and peripheral artery disease in people with HIV. The prevalence of high SIABPD was 24%, and SIABPD was independently associated with extensive coronary and peripheral arterial disease.

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.

Antiretroviral therapy (ART) in people with HIV (PWH) can lead to weight gain, but the effects of nucleoside reverse transcriptase inhibitors such as abacavir (ABC) are not well understood. In this study, we investigated whether discontinuing ABC would mitigate weight changes and metabolic complications in PWH. In a randomized controlled trial including PWH on dolutegravir, ABC, and lamivudine (DTG/ABC/3TC), participants were randomized 2:1 to either switch to DTG/3TC or continue DTG/ABC/3TC. Data was collected at baseline, week 24, and week 48. This study was powered to detect a difference of 2 kg in weight between groups. Secondary outcomes included body composition, fat and muscle distribution, and metabolic parameters. Weight and metabolic changes were analyzed by linear mixed modeling. Eighty-one participants were randomized. Switching from DTG/ABC/3TC to DTG/3TC was not associated with a significant change in weight at 48 weeks in the intention to treat (ITT) analysis (mean difference − 0.5 kg, 95% confidence interval (CI): -2.5 to 1.5, p = 0.599) or the modified ITT, (-0.1 kg, 95% CI: -1.7 to 1.5, p = 0.914). In the ITT analysis, the DTG/3TC group gained 0.4 kg ± 5.1 SD (p = 0.589) compared to 0.9 kg ± 2.3 SD (p = 0.054) in the DTG/ABC/3TC group, while in the modified ITT, the changes were 0.9 ± 3.2 kg (p = 0.054) and 0.9 ± 3.6 kg (p = 0.071), respectively. The were no differences between groups in secondary outcomes. Continuing or discontinuing abacavir for 48 weeks was associated with modest gains in weight that did not differ between groups. Similarly, fat distribution, or metabolic parameters were comparable between groups.