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Abstract Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2

SARS-CoV-2 infection is the cause of the disease named COVID-19, a major public health challenge worldwide. Differences in the severity, complications and outcomes of the COVID-19 are intriguing and, patients with similar baseline clinical conditions may have very different evolution. Myeloid-derived suppressor cells (MDSCs) have been previously found to be recruited by the SARS-CoV-2 infection and may be a marker of clinical evolution in these patients. We have studied 90 consecutive patients admitted in the hospital before the vaccination program started in the general population, to measure MDSCs and lymphocyte subpopulations at admission and one week after to assess the possible association with unfavorable outcomes (dead or Intensive Care Unit admission). We analyzed MDSCs and lymphocyte subpopulations by flow cytometry. In the 72 patients discharged from the hospital, there were significant decreases in the monocytic and total MDSC populations measured in peripheral blood after one week but, most importantly, the number of MDSCs (total and both monocytic and granulocytic subsets) were much higher in the 18 patients with unfavorable outcome. In conclusion, the number of circulating MDSCs may be a good marker of evolution in the follow-up of unvaccinated patients admitted in the hospital with the diagnosis of COVID-19.

ABSTRACT: Objectives: We evaluated the association of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) rectal colonisation with crude mortality and whether this association is independent of the risk of KPC-Kp infection. Methods: This was a prospective cohort study of patients followed-up 90 days after a study of rectal colonisation. Cox regression was used to study the variables associated with crude mortality. Sensitivity analyses for 90-day crude mortality in different subcohorts were performed. Results: A total of 1244 patients (1078 non-colonised and 166 colonised) were included. None of the non-colonised patients and 78 (47.0%) of the colonised patients developed KPC-Kp infection. The 90-day crude mortality was 18.0% (194/1078) in non-colonised patients and 41.6% (69/166) in colonised patients. Rectal colonisation was not associated with crude mortality [hazard ratio (HR) = 1.03, 95% confidence interval (CI) 0.69–1.54; P = 0.85] when the model was adjusted for severe KPC-Kp infection [INCREMENT-CPE score (ICS) > 7]. KPC-Kp infection with ICS > 7 was associated with an increased risk of all-cause mortality (HR = 2.21, 95% CI 1.35–3.63; P = 0.002). In the sensitivity analyses, KPC-Kp colonisation was not associated with mortality in any of the analysed subcohorts, including patients who did not develop KPC-Kp infection (HR = 0.93, 95% CI 0.60–1.43; P = 0.74). Conclusion: KPC-Kp rectal colonisation was not associated with crude mortality. Mortality increased when colonised patients developed severe KPC-Kp infection (ICS > 7). Rectal colonisation was a necessary although insufficient condition to die from a KPC-Kp infection.

Summary: Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74–15.53;

ABSTRACT Colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) is associated with the risk of developing KPC-Kp infection. The impact of the time elapsed since a patient becomes colonized on this risk is not well known. An observational, prospective, longitudinal cohort study of colonized patients undergoing active rectal culture screening to rule out KPC-Kp colonization (July 2012 to November 2017). Patients with a positive culture at inclusion (colonized at start of follow-up) and those with a negative culture at inclusion who became colonized within 90 days (colonized during follow-up) were included in the analysis. CART analysis was used to dichotomize variables according to their association with infection. Kaplan–Meier infection-free survival curves and the log-rank test were used for group comparisons. Logistic regression was used to identify variables associated with KPC-Kp infection. Among 1310 patients included, 166 were colonized at the end of follow-up. Forty-seven out of 118 patients colonized at start of follow-up developed infection (39.8%) versus 31 out of 48 patients colonized during follow-up (64.6%; P = 0.006). Variables associated with KPC-Kp infection in the logistic regression analysis were: colonization detection during follow-up (OR, 2.74; 95% CI, 1.07 to 7.04; P = 0.03), Giannella risk score (OR, 1.51; 95% CI, 1.32 to 1.73; P < 0.001), high-risk ward (OR, 4.77; 95% CI, 1.61 to 14.10; P = 0.005) and urological manipulation after admission (OR, 3.69; 95% CI, 1.08 to 12.60; P = 0.04). In 25 out of 31 patients (80.6%) colonized during follow-up who developed KPC-Kp infection, infection appeared within 15 days after colonization. The risk of KPC-Kp infection was higher when colonization is recently acquired during hospitalization. In this prospective study, we concluded that the timing of colonization was a factor to assess when considering empirical treatment for suspected KPC-Kp infection and prophylaxis or infection control. IMPORTANCE In this study, it was confirmed that patients who became colonized during hospitalization had a higher risk of developing KPC-Kp infection than hospitalized patients who were already colonized at the start of follow-up. Besides, the risk of infection in the group of patients who became colonized during follow-up was greater in the first weeks immediately after colonization was confirmed. Our findings support the need for designing preventive strategies for patients at the highest risk of infection development, including those admitted in high-risk hospital wards and those undergoing urological procedures.

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129–0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324–1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease.

Introduction Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E.Methods and analysis Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7–10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population.Ethics and dissemination The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals.Trial registration number NCT04478721.

Abstract Background Escherichia coli sequence type 131 (ST131) is a successful clonal group that has dramatically spread during the last decades and is considered an important driver for the rapid increase of quinolone resistance in E. coli. Methods Risk factors for rectal colonization by ST131 Escherichia coli (irrespective of ESBL production) were investigated in 64 household members (18 were colonized) and 54 hospital contacts (HC; 10 colonized) of 34 and 30 index patients with community and nosocomial infection due to these organisms, respectively, using multilevel analysis with a p limit of