Jesus Bano-Rodriguez

Description:BackgroundEvolution of SARS-CoV-2 is continuous.AimBetween 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.MethodsIn nasopharyngeal swabs of COVID-19 patients (n = 1,762) from France, Italy, Spain, and the Netherlands, SARS-CoV-2 was investigated by reverse transcription-quantitative PCR and whole-genome sequencing, and the virus variant/lineage (NextStrain/Pangolin) was determined. Patients' demographic and clinical details were recorded. Associations between mild/moderate or severe COVID-19 and SARS-CoV-2 variants and patient characteristics were assessed by logistic regression. Rates and genomic locations of mutations, as well as quasi-species distribution (≥ 2 heterogeneous positions, ≥ 50× coverage) were estimated based on 1,332 high-quality sequences.ResultsOverall, 11 SARS-CoV-2 clades infected 1,762 study patients of median age 59 years (interquartile range (IQR): 45-73), with 52.5% (n = 925) being male. In total, 101 non-synonymous substitutions/insertions correlated with disease prognosis (severe, n = 27; mild-to-moderate, n = 74). Several hotspots (mutation rates ≥ 85%) occurred in Alpha, Delta, and Omicron variants of concern (VOCs) but none in pre-Alpha strains. Four hotspots were retained across all study variants, including spike:D614G. Average number of mutations per open-reading-frame (ORF) increased in the spike gene (average < 5 per genome in January 2020 to > 15 in 2022), but remained stable in ORF1ab, membrane, and nucleocapsid genes. Quasi-species were most prevalent in 20A/EU2 (48.9%), 20E/EU1 (48.6%), 20A (38.8%), and 21K/Omicron (36.1%) infections. Immunocompromised status and age (≥ 60 years), while associated with severe COVID-19 or death irrespective of variant (odds ratio (OR): 1.60-2.25; p ≤ 0.014), did not affect quasi-species' prevalence (p > 0.05).ConclusionSpecific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs' emergence are relevant to consider.

Description:The development of predictive mortality scores for bacteraemia is fundamental for identifying patients in whom increasing our management efforts. However, it is necessary to assess the validity of the results obtained when they are applied to new cohorts. We evaluated the ability of different scales (Charlson, also age-adjusted Charlson and updated Charlson, SOFA, Pitt, INCREMENT-ESBL and BSIMRS) to predict 30-day mortality in bacteraemia through the AUROC and calibration plots. The scales were applied to specific patient from PROBAC cohort (prospective, multicentre with bacteraemia of any aetiology) according to the population in which the scale was originally developed. We also applied the recently developed PROBAC score (this time applied to the entire PROBAC cohort, rather than only to patients who did not die within 48 h of blood culture collection as in the original development of the scale). After applying Charlson, age-adjusted Charlson, updated Charlson, SOFA, Pitt and PROBAC to the entire PROBAC cohort, we obtained AUROC values: 0.60 (95% CI: 0.58-0.62); 0.62 (95% CI: 0.60-0.64); 0.60 (95% CI: 0.58-0.62); 0.69 (95% CI: 0.66-0.71); 0.71 (95% CI: 0.69-0.82) and 0.80 (95% CI: 0.79-0.81), respectively. INCREMENT-ESBL was applied only to gram negative bacteraemia yielding 0.81 (95% CI: 0.79-0.82) and BSIMRS to gram negative bacteraemia who received adequate empirical antibiotic yielding 0.72 (95% CI: 0.70-0.75). Scores that have been developed in bacteraemia cohorts and have been used for the prediction of short-term mortality were found to be better at predicting mortality in our analysis.

Description:Background: Escherichia coli is the most frequent cause of bacteraemia and has a major impact on morbidity and mortality. The aim of this study is to define and internally validate a predictive risk score of 30-day all-cause mortality. Methods: A prospective, multicentre, cohort study conducted in 26 Spanish hospitals between October 2016 and March 2017 was performed. All monomicrobial E. coli bloodstream infections (BSIs) were included. The primary outcome was 30-day all-cause mortality. Cases were randomized to a derivation cohort (DC) and a validation cohort (VC). The predictive score was calculated from a multivariable model performed by logistic regression in the DC and subsequently applied to the VC. The predictive ability of the model was estimated by calculating the area under the ROC curve (AUROC) and the goodness of fit by Hosmer-Lemeshow test and calibration plot. Results: Overall, 1435 cases were included in the DC and 715 in the VC. The final multivariable model for mortality in DC included (adjusted OR; 95% CI) age over 55 years (2.10; 1.01-4.36), dementia (2.08; 1.24-3.50), liver disease (1.81; 0.99-3.28), healthcare-associated acquisition (2.29; 1.52-3.44), Pitt index > 3 (3.59; 2.30-5.61), SOFA ≥ 2 (1.66; 1.04-2.64), and urinary tract source (0.37; 0.24-0.56). The predictive score showed an AUROC of 0.78 (95% CI 0.74-0.83) in the DC and 0.78 (95% CI 0.73-0.84) in the VC. Conclusions: We developed and internally validated a predictive scoring model to identify patients with E. coli bacteraemia at high and low risk of crude mortality on day 30 of BSI.

Description:Objective: We investigated the effectiveness of early oral switch for treating Enterobacterales bloodstream infection (BSI) by performing a post hoc emulation trial of the SIMPLIFY trial. Methods: We conducted a post hoc analysis of a randomized controlled trial. We specified the target trial characteristics selecting patients who achieved clinical stability on day 5. We categorized patients into those who switched on day 5 and those who continued intravenously. The primary outcome was clinical cure at the test of cure. We set a propensity score for being switched on day 5 to reduce confounding. We ran simple, not-propensity-adjusted, and propensity-adjusted logistic regression models to ascertain the association of switch on day 5 with clinical cure. Results: Among 303 patients who achieved clinical stability on day 5, 110 (36.3%) were switched orally on day 5, and 193 (63.7%) were kept intravenously. We detected no difference in clinical cure between those switched on day 5 and those continued intravenously (risk ratios 1.04, 95% confidence intervals [CI] 0.98-1.10). Propensity-adjusted analysis did not show an association between day 5 switch and clinical cure (OR 2.10, 95% CI 0.96-7.41). Conclusions: Oral step-down therapy on day 5 was not associated with worse clinical cure for Enterobacterales BSI.

Description:Background: Surgical antimicrobial prophylaxis (SAP) is essential for preventing surgical site infections (SSI) but is often improperly administered. This study assessed SAP adequacy and its association with SSI and other nosocomial infections (NI) to identify areas for improvement. Methods: This cross-sectional and retrospective cohort study included adults undergoing elective cardiovascular, orthopaedic, colorectal surgeries and cystectomy in 2022 at a teaching hospital. SAP was considered adequate if it met all local guideline criteria: indication, drug, dose, timing of administration, redosing and duration. Associations between SAP adequacy and SSI were analyzed using generalized mixed models. Results: Among 723 patients included (median age 68 years; 57.7% male), 714 (98.8%) received SAP. Overall multidomain adherence to SAP guidelines was 34.6%, with high compliance for regimen (92.8%), dose (97.5%), and timing (98.3%), but lower compliance for redosing (63.4%) and duration (53.9%). Regimen adequacy was significantly lower in patients with beta-lactam allergies (55.6% vs. 94.8%, p < 0.001) and in cystectomy cases compared to other procedures (41.2% vs. 94.1%, p < 0.001). Non-compliant regimens were independently associated with a higher SSI rate (adjusted OR 3.4; 95% CI: 1.8-8.3; p = 0.003), but not with non-SSI NIs. Inadequate SAP was also associated with a length of stay (LOS) exceeding 10 days (RR 4.61; p < 0.001) and higher 90-day mortality (RR 3.37; p = 0.007). Patients who developed an SSI were significantly more likely to develop additional non-SSI NIs (adjusted OR 6.1; 95% CI: 2.8-13.4; p < 0.001). Median LOS was longer in patients with SSI (16.5 vs. 7 days, p < 0.001), and SSI was also associated with increased 90-day mortality (14.7% vs. 2.7%; RR 5.42; p < 0.001). Conclusions: Non-adherence to SAP guidelines was associated with an increased risk of SSI, prolonged LOS, and greater crude mortality. Key areas for improvement include regimen selection, appropriate redosing, and limiting SAP duration. Patients with beta-lactam allergies were specially at risk of receiving inadequate SAP. Although SAP non-compliance was not independently associated with other NIs, SSIs significantly increased their occurrence.