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

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

Objectives: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. Methods: A prospective matched -cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30 -day mortality with an active postdischarge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. Results: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30 -day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55 -4.26; p &lt; 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p &lt; 0.001). The population attributable fraction for 30 -day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non -infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p &lt; 0.001), respectively. However, when treatment -related time -dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). Discussion: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality. (c) 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY -NC -ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network

Perioperative antimicrobial prophylaxis in adult patients: The first multicenter clinical practice audit with intervention in Greek surgical departments

Objective: To audit clinical practice and implement an intervention to promote appropriate use of perioperative antimicrobial prophylaxis (PAP). Design: Prospective multicenter before-And-After study. Setting: This study was conducted in 7 surgical departments of 3 major Greek hospitals. Methods: Active PAP surveillance in adults undergoing elective surgical procedures was performed before and after implementation of a multimodal intervention. The surveillance monitored use of appropriate antimicrobial agent according to international and local guidelines, appropriate timing and duration of PAP, overall compliance with all 3 parameters and the occurrence of surgical site infections (SSIs). The intervention included education, audit, and feedback. Results: Overall, 1,447 patients were included: 768 before and 679 after intervention. Overall compliance increased from 28.2% to 43.9% (P =.001). Use of antimicrobial agents compliant to international guidelines increased from 89.6% to 96.3% (P =.001). In 4 of 7 departments, compliance with appropriate timing was already &gt;90%; an increase from 44.3% to 73% (P =.001) and from 20.4% to 60% (P =.001), respectively, was achieved in 2 other departments, whereas a decrease from 64.1% to 10.9% (P =.001) was observed in 1 department. All but one department achieved a shorter PAP duration, and most achieved duration of ~2 days. SSIs significantly decreased from 6.9% to 4% (P =.026). After the intervention, it was 2.3 times more likely for appropriate antimicrobial use, 14.7 times more likely to administer an antimicrobial for the appropriate duration and 5.3 times more likely to administer an overall appropriate PAP. Conclusion: An intervention based on education, audit, and feedback can significantly contribute to improvement of appropriate PAP administration; further improvement in duration is needed. © 2021 Infection Control and Hospital Epidemiology. All rights reserved

Reducing duration of antibiotic use for presumed neonatal early-onset sepsis in greek nicus. A “low-hanging fruit” approach

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and-resource intervention to reduce antibiotic use in Greek NICUs implementing a “low-hanging fruit” approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a “low-hanging fruit” approach. In resource-limited settings, similar targeted stewardship interventions can be applied. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Central line-associated bloodstream infections in pediatric patients: Results from a national nosocomial infections surveillance program

ΟBJECTIVE To provide updated data on the rates of central line-associated bloodstream infections (CLABSI) in Greek neonatal intensive care units (NICUs), pediatric intensive care units (PICUs) and pediatric oncology units (PONCs), and to describe pathogen distribution and antimicrobial resistance patterns for CLABSIs. METHOD Active surveillance for CLABSI was conducted from June 2016 to December 2019 (43 months). A consortium of 14 NICUs, 3 PICUs, and 6 PONCs participated in the program. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the 2014 National Healthcare Safety Network criteria of the US Centers for Disease Control and Prevention (CDC). Medical records were assessed daily for calculation of CL-days, pa-tient-days, and susceptibility to isolated organisms. RESULTS A total of 519 CLABSI episodes were recorded in the 43 months. Mean CLABSI rates were 7.15 in NICUs, 5.19 in PICUs, and 2.20, per 1,000 CL-days in PONCs. A higher mean CLU ratio was reported in PONCs (0.83) and a lower mean ratio was found in NICUs (0.15). A total of 567 pathogens were isolated, the most common of which were Enterobacterales (42.1%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (14.6%), and fungi (11.5%). Among 239 (63.1%) Enterobacterales isolated, 151 were multidrug resistant. Overall, 14.8% of Gram-negative pathogens were resistant to third generation ceph-alosporins and 23.7% to carbapenems. CONCLUSIONS The rates of CLABSI and antibiotic resistance among organ-isms causing CLABSI are high in high-risk hospitalized children. These data highlight the significance of this problem and emphasize the need for implementation of infection prevention interventions. The methodology used for this surveillance program could be applied in other pediatric or adult units across Greece. © Athens Medical Society

Antifungal Prescribing in European Pediatric Intensive Care Units: Results of a Multinational 3-Month Weekly Point-Prevalence Survey

\ua9 2025 The Author(s). Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site - for further information please contact [email protected] Critically ill pediatric patients admitted to the pediatric intensive care unit (PICU) are highly vulnerable to infections, including invasive fungal diseases and antifungal agents are frequently prescribed. Little is known about antifungal usage in PICUs across Europe. Methods A multinational 3-month weekly point-prevalence study for measuring antifungal drug use was organized. Eigtheen PICUs (16 hospitals) in 10 countries in the European region participated. All patients hospitalized in the participating PICUs and receiving systemic antifungals were included. Information about ward demographics was collected once; weekly ward and patient data were collected prospectively for the 12-week study period and entered in REDCap database. Results Among 18 PICUs, 8 (44%) followed prophylactic practices for targeted group of patients, 7/18 (39%) had an antifungal stewardship program and the majority (16/18, 89%) had the capacity of biomarker utilization (16/16 galactomannan, 13/16 beta-D-glucan, and 9/16 pan-fungal PCR). One hundred one courses in equal number of patients were recorded; 14 for patients aged &lt;3 month, 87 for patients ≥3 month. Malignancy was the most common underlying condition among patients aged ≥3 month (29%) followed by surgery/trauma (25%), whereas all patients &lt;3 month had undergone a recent surgery. Indication for antifungal prescribing was prophylaxis in 38% and treatment in 62% [empirical (57%), preemptive (13%), and targeted (30%)]. Fluconazole was the most common agent both for prophylaxis and treatment, whereas liposomal amphotericin B was the most frequent agent for targeted treatment. The majority (63%) of patients on prophylaxis were oncology or transplant patients. Common reasons for empirical and targeted treatment were persistent fever/other signs of infections in high-risk patients (61%) and Candida infections (100%), respectively. For targeted treatment, the most frequent pathogens were Candida albicans (37%) and Candida parapsilosis (32%). Conclusions Most antifungal prescriptions across European PICUs were for treatment. Fluconazole was the most frequently prescribed antifungal. These surveillance data can guide antifungal stewardship strategies in PICUs