Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

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-beta-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; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Antibiotics and cure rates in childhood febrile urinary tract infections in clinical trials: a systematic review and meta-analysis

Purpose: Urinary tract infections (UTIs) are common bacterial infections among children. Objective: To systematically review the antimicrobials used for febrile urinary tract infections in pediatric clinical trials and meta-analyze the observed cure rates and reasons for treatment failure. Materials and Methods: We searched Medline, Embase and Cochrane central databases between January 1, 1990, and November 24, 2016, combining MeSH and free-text terms for: “urinary tract infections”, AND “therapeutics”, AND “clinical trials” in children (age range 0–18 years). Two independent reviewers assessed study quality and performed data extraction. The major outcome measures were clinical and microbiological cure rates according to different antibiotics. Results: We identified 2,762 published studies and included 30 clinical trials investigating 3913 cases of pediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n=2,602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant urinary tract infections have been tested in randomised clinical trials, mainly aminoglycosides. The average point cure rate of all investigational drugs was estimated to 95.3% [95% CI 93.5-96.9%]. Among 3,002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3,002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3,002) had microbiological failure. Conclusions: We observed high treatment cure rates, regardless of the investigational drug chosen, the route of administration, duration and dosing. This suggests that future research should prioritise observational studies and clinical trials on children with multi-drug resistant infections