IMPORTANCE Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use.OBJECTIVE To compare the clinical effectiveness of C-reactive protein (CRP)-guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation. DESIGN, SETTING, AND PARTICIPANTS Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019. Patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged Ն18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression.INTERVENTION Randomization in a 1:1:1 ratio to an individualized CRP-guided antibiotic treatment duration (discontinuation once CRP declined by 75% from peak; n = 170), fixed 7-day treatment duration (n = 169), or fixed 14-day treatment duration (n = 165). MAIN OUTCOMES AND MEASURESThe primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative-directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up. RESULTS Among 504 patients randomized (median [interquartile range] age, 79 [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] years; 306 of 503 [61%] were women), 493 (98%) completed 30-day follow-up and 448 (89%) completed 90-day follow-up. Median antibiotic duration in the CRP group was 7 (interquartile range, 6-10; range, 5-28) days; 34 of the 164 patients (21%) who completed the 30-day follow-up had protocol violations related to treatment assignment. The primary outcome occurred in 4 of 164 (2.4%) patients in the CRP group, 11 of 166 (6.6%) in the 7-day group, and 9 of 163 (5.5%) in the 14-day group (difference in CRP vs 14-day group, −3.1% [1-sided 97.5% CI, −ϱ to 1.1]; P < .001; difference in 7-day vs 14-day group, 1.1% [1-sided 97.5% CI, −ϱ to 6.3]; P < .001). By day 90, clinical failure occurred in 10 of 143 patients (7.0%) in the CRP group, 16 of 151 (10.6%) in the 7-day group, and 16 of 153 (10.5%) in the 14-day group.CONCLUSIONS AND RELEVANCE Among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with...
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Background The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed. Methods Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. Results Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. Conclusions Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.
Background Protecting healthcare workers (HCW) from Coronavirus Disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) seropositivity in this population. Methods Between June 22nd and August 15th 2020, employees from healthcare institutions in Northern/Eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity. Findings Among the 4664 included HCW from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19 positive household (adjusted OR=54, 95%-CI: 31-97) and stay in a COVID 19 hotspot (aOR=2.2, 95%-CI: 1.1-3.9). Blood group 0 vs. non-0 (aOR=0.4, 95%-CI: 0.3-0.7), active smoking (aOR=0.5, 95%-CI: 0.3-0.9) and living with children <12 years (aOR=0.3, 95%-CI: 0.2-0.6) were associated with decreased risk. Occupational risk factors were close contact to COVID-19 patients (aOR=2.8, 95%-CI: 1.5-5.5), exposure to COVID-19 positive co-workers (aOR=2.0, 95%-CI: 1.2-3.1), poor knowledge of standard hygiene precautions (aOR=2.0, 95%-CI: 1.3-3.2), and frequent visits to the hospital canteen (aOR=1.9, 95%-CI: 1.2-3.1). Interpretation We identified several modifiable factors associated with SARS-CoV-2 seropositivity among our HCW. Living with COVID-19 positive households showed by far the strongest association. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study. Funding Swiss National Sciences Foundation, Federal Office of Public Health, Health Department Canton of St. Gallen
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