Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients). METHODS: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied. RESULTS: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and ß-lactam/ß-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment. CONCLUSIONS: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). METHODS: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network.

PURPOSE: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture. METHODS: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality. RESULTS: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73). CONCLUSIONS: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.

Insertion site and risk of peripheral intravenous catheter colonization and/or local infection: a post hoc analysis of the CLEAN 3 study including more than 800 catheters.

AIM: Although uncommon, infections associated with peripheral intravenous catheters (PIVCs) may be responsible for severe life-threatening complications and increase healthcare costs. Few data are available on the relationship between PIVC insertion site and risk of infectious complications. METHODS: We performed a post hoc analysis of the CLEAN 3 database, a randomized 2 × 2 factorial study comparing two skin disinfection procedures (2% chlorhexidine-alcohol or 5% povidone iodine-alcohol) and two types of medical devices (innovative or standard) in 989 adults patients requiring PIVC insertion before admission to a medical ward. Insertion sites were grouped into five areas: hand, wrist, forearm, cubital fossa and upper arm. We evaluated the risk of risk of PIVC colonization (i.e., tip culture eluate in broth showing at least one microorganism in a concentration of at least 1000 Colony Forming Units per mL) and/or local infection (i.e., organisms growing from purulent discharge at PIVC insertion site with no evidence of associated bloodstream infection), and the risk of positive PIVC tip culture (i.e., PIVC-tip culture eluate in broth showing at least one microorganism regardless of its amount) using multivariate Cox models. RESULTS: Eight hundred twenty three PIVCs with known insertion site and sent to the laboratory for quantitative culture were included. After adjustment for confounding factors, PIVC insertion at the cubital fossa or wrist was associated with increased risk of PIVC colonization and/or local infection (HR [95% CI], 1.64 [0.92-2.93] and 2.11 [1.08-4.13]) and of positive PIVC tip culture (HR [95% CI], 1.49 [1.02-2.18] and 1.59 [0.98-2.59]). CONCLUSION: PIVC insertion at the wrist or cubital fossa should be avoided whenever possible to reduce the risk of catheter colonization and/or local infection and of positive PIVC tip culture.

Controlling the hospital aquatic reservoir of multidrug-resistant organisms: a cross-sectional study followed by a nested randomized trial of sink decontamination.

OBJECTIVES: The hospital water environment is an important reservoir of multidrug-resistant organisms (MDROs) and presents a risk for patient safety. We assessed the effectiveness of thermal and chemical interventions on sinks contaminated with MDRO in the hospital setting. METHODS: We conducted a cross-sectional assessment of MDRO contamination of sinks and toilets in 26 clinical wards of a tertiary care hospital. MDRO-contaminated sink traps were then replaced and randomized (1:1:1) to receive chemical (sodium hypochlorite), thermal disinfection (steam), or no intervention. Interventions were repeated weekly for 4 weeks. Sinks were resampled 7 days after the last intervention. The primary outcome was the proportion of decontaminated sinks. MDROs of interest were extended spectrum beta-lactamase (ESBL) producing and carbapenemase-producing Enterobacterales, and non-fermentative Gram-negative bacilli. RESULTS: In the cross-sectional assessment, at least one MDRO was identified in 258 (36%) of the 748 samples and in 91 (47%) of the 192 water sources. In total, 57 (42%) of the 137 sinks and 34 (62%) of the 55 toilets were contaminated with 137 different MDROs. The most common MDRO were ESBL Enterobacterales (69%, 95/137), followed by Verona Integron-Borne Metallo-ß-Lactamase (VIM) carbapenemase producing Pseudomonas aeruginosa (9%, 12/137) and Citrobacter spp. (6%, 5/137). In the nested randomized trial, five of the 16 sinks (31%) in the chemical disinfection group were decontaminated, compared with 8 of 18 (44%) in the control group (OR 0.58; 95% CI, 0.14-2.32) and 9 of 17 (53%) in the thermal disinfection group (OR 1.40; 95% CI, 0.37-5.32). DISCUSSION: Our study failed to demonstrate an added benefit of repeated chemical or thermal disinfection, beyond changing sink traps, in the MDRO decontamination of sinks. Routine chlorine-based disinfection of sinks may need to be reconsidered.

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.

BACKGROUND: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. METHODS: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. RESULTS: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045). CONCLUSIONS: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.

Surveillance of catheter-associated bloodstream infections: development and validation of a fully automated algorithm.

BACKGROUND: Most surveillance systems for catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI) are based on manual chart review. Our objective was to validate a fully automated algorithm for CRBSI and CLABSI surveillance in intensive care units (ICU). METHODS: We developed a fully automated algorithm to detect CRBSI, CLABSI and ICU-onset bloodstream infections (ICU-BSI) in patients admitted to the ICU of a tertiary care hospital in Switzerland. The parameters included in the algorithm were based on a recently performed systematic review. Structured data on demographics, administrative data, central vascular catheter and microbiological results (blood cultures and other clinical cultures) obtained from the hospital's data warehouse were processed by the algorithm. Validation for CRBSI was performed by comparing results with prospective manual BSI surveillance data over a 6-year period. CLABSI were retrospectively assessed over a 2-year period. RESULTS: From January 2016 to December 2021, 854 positive blood cultures were identified in 346 ICU patients. The median age was 61.7 years [IQR 50-70]; 205 (24%) positive samples were collected from female patients. The algorithm detected 5 CRBSI, 109 CLABSI and 280 ICU-BSI. The overall CRBSI and CLABSI incidence rates determined by automated surveillance for the period 2016 to 2021 were 0.18/1000 catheter-days (95% CI 0.06-0.41) and 3.86/1000 catheter days (95% CI: 3.17-4.65). The sensitivity, specificity, positive predictive and negative predictive values of the algorithm for CRBSI, were 83% (95% CI 43.7-96.9), 100% (95% CI 99.5-100), 100% (95% CI 56.5-100), and 99.9% (95% CI 99.2-100), respectively. One CRBSI was misclassified as an ICU-BSI by the algorithm because the same bacterium was identified in the blood culture and in a lower respiratory tract specimen. Manual review of CLABSI from January 2020 to December 2021 (n = 51) did not identify any errors in the algorithm. CONCLUSIONS: A fully automated algorithm for CRBSI and CLABSI detection in critically-ill patients using only structured data provided valid results. The next step will be to assess the feasibility and external validity of implementing it in several hospitals with different electronic health record systems.

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.

Challenges and success stories of the implementation of infection control and antimicrobial stewardship strategies: proceedings of the 5th Global Ministerial Summit on Patient Safety, 2023.

The 5th edition of the Global Ministerial Summit on Patient Safety was held in Montreux, Switzerland, in February 2023, delayed by three years due to the COVID-19 pandemic. The overarching theme of the summit was "Less Harm, Better Care - from Resolution to Implementation", focusing on the challenges of implementation of infection prevention and control (IPC) strategies as well as antimicrobial stewardship programs (ASP) around the world. IPC strategies and ASP are of increasing importance due to the substantial burden of healthcare-associated infections and antimicrobial resistance threatening patient safety. Here, we summarize countries' and regional experiences and activities related to the implementation of IPC strategies and ASP shared at the meeting. Full implementation of effective programs remains a major challenge in all settings due to limited support by political and healthcare leaders, and human and financial constraints. In addition, the COVID-19 pandemic challenged already well-established programs. By enforcing sustained implementation by dedicated, cross-disciplinary healthcare personnel with a broad skill set, a reduction in healthcare-associated infections and multidrug-resistant pathogens can be achieved, leading ultimately to improved patient safety.

Systematic scoping review of automated systems for the surveillance of healthcare-associated bloodstream infections related to intravascular catheters.

INTRODUCTION: Intravascular catheters are crucial devices in medical practice that increase the risk of healthcare-associated infections (HAIs), and related health-economic adverse outcomes. This scoping review aims to provide a comprehensive overview of published automated algorithms for surveillance of catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). METHODS: We performed a scoping review based on a systematic search of the literature in PubMed and EMBASE from 1 January 2000 to 31 December 2021. Studies were included if they evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We assessed the design of the automated systems, including the definitions used to develop algorithms (CLABSI versus CRBSI), the datasets and denominators used, and the algorithms evaluated in each of the studies. RESULTS: We screened 586 studies based on title and abstract, and 99 were assessed based on full text. Nine studies were included in the scoping review. Most studies were monocentric (n = 5), and they identified CLABSI (n = 7) as an outcome. The majority of the studies used administrative and microbiological data (n = 9) and five studies included the presence of a vascular central line in their automated system. Six studies explained the denominator they selected, five of which chose central line-days. The most common rules and steps used in the algorithms were categorized as hospital-acquired rules, infection rules (infection versus contamination), deduplication, episode grouping, secondary BSI rules (secondary versus primary BSI), and catheter-associated rules. CONCLUSION: The automated surveillance systems that we identified were heterogeneous in terms of definitions, datasets and denominators used, with a combination of rules in each algorithm. Further guidelines and studies are needed to develop and implement algorithms to detect CLABSI/CRBSI, with standardized definitions, appropriate data sources and suitable denominators.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.

KEY MESSAGES: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. BACKGROUND: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. METHODS: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock. RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. CONCLUSIONS: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.