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...
Objectives We report a case of SARS-CoV-2 reinfection 6 months after the first infection in a young healthy female physician. Both episodes led to mild COVID-19. Methods SARS-CoV-2 infections was detected by RT-PCR on naso-pharyngeal specimens. Reinfection was confirmed by whole-genome sequencing. Kinetics of total anti-S receptor binding domain immunoglobulins (Ig anti-S RBD), anti-nucleoprotein (anti-N) and neutralizing antibodies were determined in serial serum samples retrieved during both infection episodes. Memory B cells responses were assessed at day 12 post reinfection. Results Whole-genome sequencing identified two different SARS-CoV-2 genomes both belonging to clade 20A, with only one non-synonymous mutation in the spike protein, and clustered with viruses circulating in Geneva (Switzerland) at the time of each of the corresponding episodes. Seroconversion was documented with low level of total Ig anti-S RBD and anti-N antibodies at one month after the first infection whereas neutralizing antibodies quickly declined after the first episode and then were boosted by the reinfection, with high titers detectable 4 days after symptoms onset. A strong memory B cell response was detected at day 12 post onset of symptoms during reinfection, indicating that the first episode elicited cellular memory responses. Conclusion Rapid decline of neutralizing antibodies may put medical personnel at risk of reinfection as shown in this case. Reinfection however leads to a significant boosting of previous immune responses. Larger cohorts of reinfected subjects with detailed descriptions of their immune responses are needed to define correlates of protection and their duration after infection.
Background Fear of falling is highly prevalent in older adults and associated with numerous negative health events. The main objective of this study was to validate a scale to assess fear of falling, based on performance in real situation (Perform-FES), in a hospitalized geriatric population. Methods In this cross-sectional study, 55 patients (mean age: 85.3 years; 58% women) hospitalized in a geriatric hospital in Geneva (Switzerland) were enrolled. The Perform-FES scale was administered to all patients in conjunction with four other fear of falling scales. We determined the floor and ceiling effects, internal consistency, reliability, construct validity, and discriminative power of the Perform-FES scale. Results The Perform-FES scale did not demonstrate any significant floor or ceiling effect. It had a good internal consistency (Cronbach’s alpha = 0.78) and an excellent reliability (intraclass correlation coefficient = 0.94). Regarding convergent validity, good correlations were shown between the score obtained on the Perform-FES scale and those obtained on other fear of falling scales. Also, the Perform-FES scale was able to discriminate patients with severe functional impairments (area under the ROC curve = 0.81) and had significantly better discriminating performance than other fear of falling scales. Conclusion Findings suggest that the Perform-FES scale has good psychometric properties and may be a relevant tool to assess fear of falling in a geriatric hospitalized population. Future research should focus in particular on assessing the sensitivity to change and the predictive value of this scale in longitudinal studies, and its validity in other populations.
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