Retrospective validation study of a machine learning-based software for empirical and organism-targeted antibiotic therapy selection.

Errors in antibiotic prescriptions are frequent, often resulting from the inadequate coverage of the infection-causative microorganism. The efficacy of iAST, a machine-learning-based software offering empirical and organism-targeted antibiotic recommendations, was assessed. The study was conducted in a 12-hospital Spanish institution. After model fine-tuning with 27,531 historical antibiograms, 325 consecutive patients with acute infections were selected for retrospective validation. The primary endpoint was comparing each of the top three of iAST's antibiotic recommendations' success rates (confirmed by antibiogram results) with the antibiotic prescribed by the physicians. Secondary endpoints included examining the same hypothesis within specific study population subgroups and assessing antibiotic stewardship by comparing the percentage of antibiotics recommended that belonged to different World Health Organization AWaRe groups within each arm of the study. All of iAST first three recommendations were non-inferior to doctor prescription in the primary endpoint analysis population as well as the secondary endpoint. The overall success rate of doctors' empirical treatment was 68.93%, while that of the first three iAST options was 91.06% (P < 0.001), 90.63% (P < 0.001), and 91.06% (P < 001), respectively. For organism-targeted therapy, the doctor's overall success rate was 84.16%, and that of the first three ranked iAST options was 97.83% (P < 0.001), 94.09% (P < 0.001), and 91.30% (P < 0.001), respectively. In empirical therapy, compared to physician prescriptions, iAST demonstrated a greater propensity to recommend access antibiotics, fewer watch antibiotics, and higher reserve antibiotics. In organism-targeted therapy, iAST advised a higher utilization of access antibiotics. The present study demonstrates iAST accuracy in predicting antibiotic susceptibility, showcasing its potential to promote effective antibiotic stewardship. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT06174519.

kinetics of anti-SARS-CoV-2 antibodies over time. Results of 10 month follow up in over 300 seropositive Health Care Workers.

BACKGROUND: The kinetics of the antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated since long-term duration of antibody remains largely unknown, particularly in infected healthcare workers (HCW). METHODS: Prospective study, evaluating the longitudinal profile of anti-SARS-CoV-2 antibody titers in a random sample of 331 seropositive healthcare workers (HCW) of Spanish Hospitals Group. Serial measurements of serum IgG-anti-SARS-CoV-2 were obtained at baseline (April-May,2020), and in 2 follow-up visits. Linear mixed models were used to investigate antibody kinetics and associated factors. RESULTS: A total of 306 seropositive subjects (median age: 44.7years;69.9% female) were included in the final analysis. After a median follow-up of 274 days between baseline and final measurement, 235(76.8%) maintained seropositivity. Antibody titers decreased in 82.0%, while remained stable in 13.1%. Factors associated with stability of antibodies over time included age≥45 years, higher baseline titers, severe/moderate infection and high-grade exposure to COVID-19 patients. In declining profile, estimated mean antibody half-life was 146.3 days(95%CI:138.6-154.9) from baseline. Multivariate models show independent longer durability of antibodies in HCW with high-risk exposure to COVID-19 patients (+14.1 days;95%CI:0.6-40.2) and with symptomatic COVID-19 (+14.1 days;95%CI:0.9-43.0). The estimated mean time to loss antibodies was 375(95% CI:342-408) days from baseline. CONCLUSIONS: We present the first study measuring the kinetics of antibody response against SARS-CoV-2 in HCW beyond 6 months. Most participants remained seropositive after 9 months but presented a significant decline in antibody-titers. Two distinct antibody dynamic profiles were observed (declining vs. stable). Independent factors associated with longer durability of antibodies were symptomatic infection and higher exposure to COVID-19 patients.

Seroprevalence of SARS-CoV-2 antibodies in over 6000 healthcare workers in Spain.

BACKGROUND: Spain has one of the highest incidences of coronavirus disease 2019 (COVID-19) worldwide, so Spanish health care workers (HCW) are at high risk of exposure. Our objective was to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence amongst HCW and factors associated with seropositivity. METHODS: A cross-sectional study evaluating 6190 workers (97.8% of the total workforce of a healthcare-system of 17 hospitals across four regions in Spain) was carried out between April and June 2020, by measuring immunoglobulin G (IgG)-SARS-CoV-2 antibody titres and related clinical data. Exposure risk was categorized as high (clinical environment; prolonged/direct contact with patients), moderate (clinical environment; non-intense/no patient contact) and low (non-clinical environment). RESULTS: A total of 6038 employees (mean age 43.8 years; 71% female) were included in the final analysis. A total of 662 (11.0%) were seropositive for IgG against SARS-CoV-2 (39.4% asymptomatic). Adding available PCR-testing, 713 (11.8%) employees showed evidence of previous SARS-CoV-2 infection. However, before antibody testing, 482 of them (67%) had no previous diagnosis of SARS-CoV-2-infection. Seroprevalence was higher in high- and moderate-risk exposure (12.1 and 11.4%, respectively) compared with low-grade risk subjects (7.2%), and in Madrid (13.8%) compared with Barcelona (7.6%) and Coruña (2.0%). High-risk [odds ratio (OR): 2.06; 95% confidence interval (CI): 1.63-2.62] and moderate-risk (OR: 1.77; 95% CI: 1.32-2.37) exposures were associated with positive IgG-SARS-CoV-2 antibodies after adjusting for region, age and sex. Higher antibody titres were observed in moderate-severe disease (median antibody-titre: 13.7 AU/mL) compared with mild (6.4 AU/mL) and asymptomatic (5.1 AU/mL) infection, and also in older (>60 years: 11.8 AU/mL) compared with younger (<30 years: 4.2 AU/mL) people. CONCLUSIONS: Seroprevalence of IgG-SARS-CoV-2 antibodies in HCW is a little higher than in the general population and varies depending on regional COVID-19 incidence. The high rates of subclinical and previously undiagnosed infection observed in this study reinforce the utility of antibody screening. An occupational risk for SARS-CoV-2 infection related to working in a clinical environment was demonstrated in this HCW cohort.