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Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents.

Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs. We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios. We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90–2·37) and vancomycin-resistant enterococci (0·63, 0·39–1·02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0·73, 0·51–1·05) or fluoroquinolone-resistance (0·52, 0·16–1·68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46–0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20–0·52) in recipients of selective decontamination compared with those who received no intervention. We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates. None.

ObjectivesFluoroquinolone-associated tendon ruptures are a recognised complication, but other severe collagen-associated adverse events may also be possible. Our objectives were to confirm the association of fluoroquinolones and tendon rupture, to clarify the potential association of fluoroquinolones and retinal detachment, and to test for a potentially lethal association between fluoroquinolones and aortic aneurysms.SettingPopulation-based longitudinal cohort study in Ontario, Canada.ParticipantsOlder adults turning 65 years between April 1 1997 and March 31 2012 were followed until primary outcome, death, or end of follow-up (March 31 2014). Fluoroquinolone prescriptions were measured as a time-varying covariate, with patients considered at risk during and for 30 days following a treatment course.Primary outcome measuresSevere collagen-associated adverse events defined as tendon ruptures, retinal detachments and aortic aneurysms diagnosed in hospital and emergency departments.ResultsAmong the 1 744 360 eligible patients, 657 950 (38%) received at least one fluoroquinolone during follow-up, amounting to 22 380 515 days of treatment. The patients experienced 37 338 (2.1%) tendon ruptures, 3246 (0.2%) retinal detachments, and 18 391 (1.1%) aortic aneurysms. Severe collagen-associated adverse events were more common during fluoroquinolone treatment than control periods, including tendon ruptures (0.82 vs 0.26/100-person years, p<0.001), retinal detachments (0.03 vs 0.02/100-person-years, p=0.003) and aortic aneurysms (0.35 vs 0.13/100-person-years, p<0.001). Current fluoroquinolones were associated with an increased hazard of tendon rupture (HR 3.13, 95% CI 2.98 to 3.28; adjusted HR 2.40, 95% CI 2.24 to 2.57) and an increased hazard of aortic aneurysms (HR 2.72, 95% CI 2.53 to 2.93; adjusted HR2.24, 95% CI 2.02 to 2.49) that were substantially greater in magnitude than the association of these outcomes with amoxicillin. The hazard of retinal detachment was marginal (HR 1.28, 95% CI 0.99 to 1.65; adjusted HR 1.47, 95% CI 1.08 to 2.00) and not greater in magnitude than that observed with amoxicillin.ConclusionsFluoroquinolones are associated with subsequent tendon ruptures and may also contribute to aortic aneurysms.

Background. Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of these reported allergies on clinical outcomes. Methods. We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. Results. Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When betalactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28–7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62–2.87). Conclusions. Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.

A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir–ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir–ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate. We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir–ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1–30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir–ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir–ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47–0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39–0.62). Our findings were similar across strata of age, drug–drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43–80), which varied across strata. Nirmatrelvir–ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease.

Abstract Background Antimicrobial stewardship programs (ASPs) using audit and feedback in the intensive care unit (ICU) setting can reduce harms related to inappropriate antibiotic use. However, inappropriate discontinuation or narrowing of antibiotic treatment could increase infection-related mortality in this population. Individual ASP studies are underpowered to detect differences in mortality. Methods We conducted a systematic review and meta-analysis of audit and feedback in the ICU setting, using mortality as our outcome. Results Of 2447 citations, 11 studies met our inclusion criteria. Although a variety of study designs were used to assess reductions in antibiotic use, mortality was analyzed using an uncontrolled before-after study design in all studies. Five studies directed audit and feedback to all or most ICU patients receiving antibiotics and measured overall ICU mortality. In the meta-analysis of these studies, the pooled relative risk of ICU mortality was 1.03 (95% confidence interval, .93–1.14). A second meta-analysis of 3 smaller studies that evaluated mortality only in patients directly assessed by the ASP found a pooled relative risk of ICU mortality of 1.06 (95% confidence interval, .80 to 1.4). Three studies were not appropriate for meta-analysis, but their results were consistent with our overall findings. Conclusions Our systematic review did not identify a change in mortality associated with antimicrobial stewardship using audit and feedback in the ICU setting. These results increase our confidence that audit and feedback can be safely implemented in this setting. Future studies should report standardized estimates of mortality and use more robust study designs to assess mortality, when feasible. Our systematic review of antimicrobial stewardship programs using audit and feedback in the ICU setting found no change in mortality rates with implementation of the intervention and increases our confidence in the safety of antimicrobial stewardship, even in high-risk settings.

The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection. We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex. Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI −0.67 to −0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (−27.31) and outpatient (−0.87) encounters. We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

We aimed to estimate associations between COVID-19 incidence and mortality with neighbourhood-level immigration, race, housing, and socio-economic characteristics. We conducted a population-based study of 28,808 COVID-19 cases in the provincial reportable infectious disease surveillance systems (Public Health Case and Contact Management System) which includes all known COVID-19 infections and deaths from Ontario, Canada reported between January 23, 2020 and July 28, 2020. Residents of congregate settings, Indigenous communities living on reserves or small neighbourhoods with populations <1,000 were excluded. Comparing neighbourhoods in the 90th to the 10th percentiles of socio-demographic characteristics, we estimated the associations between 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics and COVID-19 incidence and mortality using Poisson generalized linear mixed models. Neighbourhoods with the highest proportion of immigrants (relative risk (RR): 4.0, 95%CI:3.5-4.5) and visible minority residents (RR: 3.3, 95%CI:2.9-3.7) showed the strongest association with COVID-19 incidence in adjusted models. Among individual race groups, COVID-19 incidence was highest among neighbourhoods with the high proportions of Black (RR: 2.4, 95%CI:2.2-2.6), South Asian (RR: 1.9, 95%CI:1.8-2.1), Latin American (RR: 1.8, 95%CI:1.6-2.0) and Middle Eastern (RR: 1.2, 95%CI:1.1-1.3) residents. Neighbourhoods with the highest average household size (RR: 1.9, 95%CI:1.7-2.1), proportion of multigenerational families (RR: 1.8, 95%CI:1.7-2.0) and unsuitably crowded housing (RR: 2.1, 95%CI:2.0-2.3) were associated with COVID-19 incidence. Neighbourhoods with the highest proportion of residents with less than high school education (RR: 1.6, 95%CI:1.4-1.8), low income (RR: 1.4, 95%CI:1.2-1.5) and unaffordable housing (RR: 1.6, 95%CI:1.4-1.8) were associated with COVID-19 incidence. Similar inequities were observed across neighbourhood-level sociodemographic characteristics and COVID-19 mortality. Neighbourhood-level inequities in COVID-19 incidence and mortality were observed in Ontario, with excess burden experienced in neighbourhoods with a higher proportion of immigrants, racialized populations, large households and low socio-economic status.

Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS). In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection. We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1). An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage.

Long COVID impacts people's physical health and cognition which immensely affects their psychosocial well-being. A larger study was conducted that explored the psychosocial impacts of Long COVID on individuals and caregivers. This paper focuses on the impact of these stressful disruptions on one's health and psychosocial well-being, and how individuals cope with them. Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with Long COVID (mean age: 50.4) and 15 caregivers (mean age: 50.0)). People with Long COVID and caregivers were recruited from healthcare institutions through care team referrals, patient partners, and health organizations and via social media platforms. A thematic codebook developed through inter-coder agreement processes was used to analyze the data. Three key themes were identified: (1) Disruptions in people with Long COVID and caregivers' lives are characterized by a deviation from their perceived 'normalcy', (2) Disruptions lead to substantial stress, loss and grief (independence, agency, meaning, and purpose), and (3) People with Long COVID and caregivers cope with stressful disruptions by adapting their daily activities. Our findings make the case for supportive rehabilitation strategies that address the psychosocial repercussions of Long COVID to help mitigate feelings of loss and grief, thereby increasing individuals' overall quality of life and well-being.