Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study

Bloodstream infection; COVID-19; EnterococcusInfección del torrente sanguíneo; COVID-19; EnterococoInfecció del torrent sanguini; COVID-19; EnterococBackground The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019.Research grants were obtained from the European society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund. Dr. Buetti received a grant from the Swiss National Science Foundation (Grant Number: P4P4PM_194449). The study was endorsed by the critically ill group of the ESCMID (ESGCIP) and by the infection group of the ESICM with scientific input of the OUTCOMEREA network

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

IMPORTANCE Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. OBJECTIVE To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. EVIDENCE REVIEW This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. FINDINGS A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. CONCLUSIONS AND RELEVANCE In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed

1411. Tecioplanin (Tei) Vs. Vancomycin (Van) In Combination With Piperacillin-Tazobactam (Tzp) Or Meropenem (Mer) As A Cause Of Acute Kidney Injury (Aki)

Background VAN has been shown to cause increased incidence of AKI when combined with TZP. The reason is unknown. TEI is a glycopeptide which may be less nephrotoxic. We compared both glycopeptides in combination with TZP or MER for causing AKI. Methods A retrospective cohort study was performed between May 2015 and December 2017 in a large tertiary care setting. Evaluation of AKI was made by using RIFLE criteria. Patients ≥18 years were included if they had a baseline serum creatinine available and received one of the combinations tested for at least 48 hours. Exclusion criteria were renal replacement therapy, pregnancy, <48 hours antibiotic therapy and no follow-up. Results Overall 456 patients were screened and 379 included in the study. After controlling for residual differences (age, Charlson comorbidity index score, presence of AKI, GFR value, presence of sepsis or septic shock, residing in intensive care unit at the time of antibiotic therapy and number of days of antibiotic therapy), AKI incidence was significantly higher in patients receiving TZP-VAN than those receiving TZP-TEI and also in patients receiving TZP-VAN than those with MER-VAN. No difference in AKI was detected between patients with MER-VAN and with MER-TEI (table). Mortality at 7 and 30 days and resolution of AKI at discharge were similar in all groups., Conclusion TZP causes increased nephrotoxicity when combined with VAN. Combination with TEI may offset this side effect. Additionally, the higher AKI incidence with TZP-VAN than MER-VAN may suggest a particular nephrotoxic synergy between TZP and VAN. Randomized controlled trials should confirm this observation. Disclosures All authors: No reported disclosures.PubMe

Comparison of three different regimens against Helicobacter pylori as a first-line treatment: A randomized clinical trial

Treatments with bismuth-containing quadruple therapy (QT), sequential therapy (ST), or concomitant therapy (CT) have been proposed as empirical first-line regimens for Helicobacter pylori. We compared the efficacy and tolerability of 10 days bismuth-containing quadruple QT, 10 days ST, and 10 days CT with as first-line treatments for H. pylori in a randomized crossover study. The subjects were randomly divided into three groups. The first 130 patients were treated with rabeprazole, bismuth potassium citrate, metronidazole, and tetracycline for 10 days. The second 130 patients in the sequential group were treated with rabeprazole and amoxicillin for 5 days, and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. The last 130 patients in the concomitant group were treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 10 days. H. pylori eradication was confirmed by urea breath test at 6 weeks. The primary outcome was eradication rates of first-line treatment by intention to treat and per protocol (PP) analyzes. There was no difference between the average ages and the male/female ratio of the groups. The PP analysis was performed on 121, 119, and 118 patients in the QT, ST, and CT groups, respectively. In the PP analysis, the successful eradication 94.2% (114/121), 95.0% (113/119), and 95.8% (113/118) the QT, ST, and CT groups, respectively. There was no significant difference among the three groups (p = 0.86). 10 days QT, ST, and CT are highly effective as empirical first-line therapies for H. pylori in the region with high clarithromycin resistance

In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review

Introduction: Carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections. Methods: We systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded. Results: 22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies. Discussion: The benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552

2277. Comparison Of 30-Day Crude Mortality Rates In Patients With Bloodstream Infections (Bsis) Caused By Colistin Susceptible-(Cols-Crkp) Vs. Colistin And Carbapenem-Resistant Klebsiella Pneumoniae(Colr-Crkp)

Background Colistin is a last resort antibiotic against infections with CRKp. Its increased use has led to resistance to this antibiotic. Methods This was a single-center, retrospective, cohort study including all CRKp BSIs treated between January 1, 2014 and July 31, 2018. Antibiotic therapy was appropriate if initiated within 5 days from the onset of BSI including at least an active drug with an adequate dosage. Exclusion criteria were missing key data, death < 24 h after inclusion, subsequent episodes in the same patients, pregnancy, polymicrobial BSI, < 18 years of age, no ID consultation, no carbapenemase gene detection by multiplex PCR for blaKPC, blaNDM, blaVIM, blaIMPand blaOXA48. EUCAST breakpoints were used for antibiotic susceptibilities. Colistin MIC was determined by using broth microdilution. FDA criteria were applied for tigecycline susceptibility Results Among 174 CRKp BSIs, 129 met all inclusion criteria. Susceptibility to antibiotics was as follows: colistin (51.9%), tigecycline (67.4%), gentamicine (38.0%), amikacin (43.0%), meropenem (32.6%), ciprofloxacin (18.6%), TMP-SMX (24.0%), ceftazidime (7.8%), cefepime (7.8%)., 66.1% and 19.4% of the patients received inappropriate therapy in ColR-CRKp and ColS-CRKp groups, respectively (P ≤ 0.001). We incorporated interaction between colistin susceptibility and inappropriate therapy into multivariate logistic regression analysis (MLRA) that was constructed for identification of independent risk factors for 30-day mortality. The variables having P ≤ 0.1 in crude analysis were included in MLRA. After checking correlation between variables by Pearson correlation analysis and multicollinearity analysis, the final model was builded. The results are shown in Table 2. Conclusion Colistin resistance and inappropriate therapy were not associated with decreased mortality individually, however their interaction significantly increased 30-day mortality rate (OR: 4.04; 95% CI: 1.62–10.02; P = 0.003).85.5% of ColR-CRKp isolates produced an OXA-48 enzyme which can be inhibited by ceftazidime–avibactam, but not available in our setting, treatment with this agent may have altered the mortality rates. Thus, high rate colistin resistance among CRKp isolates remains as a significant cause of mortality in our setting., , , , Disclosures All authors: No reported disclosures.PubMe

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study.

BACKGROUND: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. METHODS: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. RESULTS: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49-2.45). CONCLUSIONS: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund. Dr. Buetti received a grant from the Swiss National Science Foundation (grant number: P4P4PM_194449). Dr. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1). Dr. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1). Dr. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1)

Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study.

Funder: European Society of Clinical Microbiology and Infectious DiseasesFunder: Norva Dahlia foundationFunder: Redcliffe Hospital Private Practice Trust FundFunder: European Society of Intensive Care MedicinePURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.Professor Jan de Waele is a senior clinical investigator funded by the Research Foundation Flanders (FWO, Ref. 1881020N). Doctor Andrew Conway Morris is supported by a Medical Research Council Clinician Scientist Fellowship (MR/V006118/1). Doctor Niccolò Buetti received a fellowship grant (Grant number: P4P4PM_194449) from the Swiss National Science Foundation The Eurobact 2 study was endorsed by the European Society of Intensive Care Medicine (ESICM), the infection section of the ESCIM and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), with scientific input of the OUTCOMEREA networ

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.Clinician Scientist Fellowship grant number: MR/V006118/1