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Objectives: Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases., Methods: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure., Results: Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%-76.1%, interquartile range 19.6%-41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77-.88, P < .0001; translating to absolute risk reduction of -3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source)., Conclusions: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI., Methods: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders., Results: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism., Conclusions: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: The role of antibiotics in preventing urinary tract infection (UTI) in older adults is unknown. We sought to quantify the benefits and risks of antibiotic prophylaxis among older adults., Methods: We conducted a matched cohort study comparing older adults (≥66 years) receiving antibiotic prophylaxis, defined as antibiotic treatment for ≥30 days starting within 30 days of a positive culture, with patients with positive urine cultures who received antibiotic treatment but did not receive prophylaxis. We matched each prophylaxis recipient to 10 nonrecipients based on organism, number of positive cultures, and propensity score. Outcomes included (1) emergency department (ED) visit or hospitalization for UTI, sepsis, or bloodstream infection within 1 year; (2) acquisition of antibiotic resistance in urinary tract pathogens; and (3) antibiotic-related complications., Results: Overall, 4.7% (151/3190) of UTI prophylaxis patients and 3.6% (n = 1092/30 542) of controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12-1.57). Acquisition of antibiotic resistance to any urinary antibiotic (HR, 1.31; 95% CI, 1.18-1.44) and to the specific prophylaxis agent (HR, 2.01; 95% CI, 1.80-2.24) was higher in patients receiving prophylaxis. While the overall risk of antibiotic-related complications was similar between groups (HR, 1.08; 95% CI, .94-1.22), the risk of Clostridioidesdifficile and general medication adverse events was higher in prophylaxis recipients (HR [95% CI], 1.56 [1.05-2.23] and 1.62 [1.11-2.29], respectively)., Conclusions: Among older adults with UTI, the harms of long-term antibiotic prophylaxis may outweigh their benefits., (Her Majesty the Queen in Right of Canada, as represented by the Public Health Ontario, 2021.)

Background: Antibiotic use is the strongest modifiable risk factor for the development of Clostridioides difficile infection, but prescribers lack quantitative information on comparative risks of specific antibiotic courses. Our objective was to estimate risks of C. difficile infection associated with receipt of specific antibiotic courses., Methods: We conducted a longitudinal case-cohort analysis representing over 90% of Ontario nursing home residents, between 2012 and 2017. Our primary exposure was days of antibiotic receipt in the prior 90 days. Adjustment covariates included: age, sex, prior emergency department or acute care stay, Charlson comorbidity index, prior C. difficile infection, acid suppressant use, device use, and functional status. We examined incident C. difficile infection, including cases identified within the nursing home, and those identified during subsequent hospital admissions. Adjusted and unadjusted regression models were used to measure risk associated with 5- to 14-day courses of 18 different antibiotics., Results: We identified 1708 cases of C. difficile infection (1.27 per 100 000 resident-days). Longer antibiotic duration was associated with increased risk: 10- and 14-day courses incurred 12% (adjusted relative risk [ARR] = 1.12, 95% confidence interval [CI]: 1.09, 1.14) and 27% (ARR = 1.27, 95% CI: 1.21,1.30) more risk compared to 7-day courses. Among 7-day courses with similar indications: moxifloxacin resulted in 121% more risk than amoxicillin (ARR = 2.21, 95% CI: 1.67, 3.08), ciprofloxacin engendered 89% more risk than nitrofurantoin (ARR = 1.89, 95% CI: 1.45, 2.68), and clindamycin resulted in 112% (ARR = 2.12, 95% CI: 1.32, 3.78) more risk than cloxacillin., Conclusions: C. difficile infection risk increases with antibiotic duration, and there are wide disparities in risks associated with antibiotic courses used for similar indications., (Her Majesty the Queen in Right of Canada, as represented by the Public Health Ontario, 2020.)

Background: Abdominal imaging is important in managing inflammatory bowel disease (IBD). We characterized utilization of imaging and exposure to ionizing radiation., Methods: We enumerated abdominal diagnostic imaging in a population-based cohort of IBD patients between 1994 and 2016. Trends in utilization of abdominal computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound were characterized. Cumulative doses of ionizing radiation were compared between IBD patients and non-IBD controls and between Crohn's disease (CD) and ulcerative colitis (UC) patients. Regression models were constructed to assess predictors of high ionizing radiation exposure., Results: There were 72,933 incident cases of IBD. During the first 5 years of diagnosis, IBD patients were exposed to nearly 6-fold higher exposure to cumulative ionizing radiation attributable to abdominal imaging compared with non-IBD controls (18.6 mSv vs 2.9 mSv). Cumulative ionizing radiation exposure was higher in CD than UC (26.0 mSv vs 12.0 mSv; P < 0.001). Crohn's disease patients were more than twice as likely as UC patients to exceed 50 mSv (15.6% vs 6.2%; P < 0.001) and 100 mSV (5.0% vs 2.1%; P < 0.001). There was geographic variation in ionizing radiation exposure, and individuals of lower income were more likely to have high exposure. Utilization of abdominal MRI has increased substantially, peaking between 2007 and 2012 and increasing annually at 34%, which coincided with an annual 2% decline in the use of abdominal CT., Conclusions: Crohn's disease patients are at highest risk for high exposure to ionizing radiation, with a subgroup receiving potentially harmful levels. Increasing utilization and access to abdominal MRI may alleviate exposure., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rates of antibiotic use vary widely across nursing homes and cannot be explained by resident characteristics. Antibiotic prescribing for a presumed urinary tract infection is often preceded by inappropriate urine culturing. We examined nursing home urine-culturing practices and their association with antibiotic use., Methods: We conducted a longitudinal, multilevel, retrospective cohort study based on quarterly nursing home assessments between April 2014 and January 2017 in 591 nursing homes and covering >90% of nursing home residents in Ontario, Canada. Nursing home urine culturing was measured as the proportion of residents with a urine culture in the prior 14 days. Outcomes included receipt of any systemic antibiotic and any urinary antibiotic (eg, nitrofurantoin, trimethoprim/sulfonamides, ciprofloxacin) in the 30 days after the assessment and Clostridiodes difficile infection in the 90 days after the assessment. Adjusted Poisson regression models accounted for 14 resident covariates., Results: A total of 131 218 residents in 591 nursing homes were included; 7.9% of resident assessments had a urine culture in the prior 14 days; this proportion was highly variable across the 591 nursing homes (10th percentile = 3.4%, 90th percentile = 14.3%). Before and after adjusting for 14 resident characteristics, nursing home urine culturing predicted total antibiotic use (adjusted risk ratio [RR] per doubling of urine culturing, 1.21; 95% confidence interval [CI], 1.18-1.23), urinary antibiotic use (RR, 1.33; 95% CI, 1.28-1.38), and C. difficile infection (incidence rate ratio, 1.18; 95% CI, 1.07-1.31)., Conclusions: Nursing homes have highly divergent urine culturing rates; this variability is associated with higher antibiotic use and rates of C. difficile infection., (Her Majesty the Queen in Right of Canada, as represented by the Public Health Ontario, 2019.)

Background and Aims: The number of inflammatory bowel disease [IBD]-related visits to the emergency department [ED] is increasing in North America. This study evaluates the relationship between access to specialists and utilization of ED services., Methods: We conducted a population-based study of all IBD patients in Ontario in 2014-2015 to measure utilization of non-emergency IBD care by specialists [NICS] and ED visits. After characterizing regional variation in access to gastroenterologists and region-wide implementation of NICS, we constructed regression models to determine whether they were predictors of individual utilization of NICS and ED services., Results: The number of gastroenterologists per 1000 IBD patients varied geographically, ranging from 1.13 to 10.65, as did the region-wide proportion of patients who received NICS, ranging from 21% to 52%. Compared with those with low access to gastroenterologists, those living in areas with moderate (odds ratio [OR], 2.37; 95% confidence interval [CI]: 2.27-2.47) and high [OR, 1.83; 95% CI: 1.71-1.95] access were more likely to receive NICS. The risk of visits to the ED was lower among those residing in regions with moderate [OR, 0.78; 95% CI: 0.75-0.82] and high access [OR, 0.74; 95% CI: 0.69-0.80] to gastroenterologists and in regions where implementation of NICS was not low [OR, 0.78; 95% CI: 0.75-0.81]., Conclusions: Poor access to outpatient IBD specialist care contributes to IBD-related ED visits. Strategies to increase specialist access may reduce the utilization of emergency services., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)-uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women., Methods: In this prospective cohort study, longitudinal mtDNA:nuclear DNA and mtRNA:beta-actin mRNA ratios were compared in blood samples obtained at various time points from birth to 8 months, using generalized estimating equation linear regression models., Results: Log(10) mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance (P = .07 for comparison of samples obtained 0-3 days after birth). ART-exposed infants' mtDNA levels increased further during the zidovudine prophylaxis period-from age 4 days to age 6 weeks-(P = .001) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log(10) mtRNA levels at birth were lower in ART-exposed infants than in control infants (P = .03), but were not statistically different later., Conclusions: When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied.