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Background: Data sharing accelerates scientific progress and improves evidence quality. Even though journals and funding institutions require investigators to share data, only a small part of studies made their data publicly available upon publication. The procedures necessary to share retrospective data for re-use in secondary data analysis projects can be cumbersome., Objectives: Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance (PrIMAVeRa) is a European research project that aims to develop mathematical models and an epidemiological repository to assess the impact of vaccines and monoclonal antibodies on antimicrobial resistance (AMR). To accomplish the project aim, Work Package 3 was responsible for gathering historical anonymized individual patient datasets., Sources: Through a systematic search we have identified 108 eligible studies for data sharing; of which eight have completed all legal requirements and shared their datasets, with data from four infectious syndromes and seven resistant pathogens. The AMR data gathered in PrIMAVeRa project is publicly available in European Clinical Research Alliance on Infectious Disease epidemiology network platform (https://epi-net.eu/primavera/about/anonymized-individual-patient-data/)., Content: Challenges and possible solutions in data sharing activities were mapped and discussed: lack of researchers' interest in sharing data, cumbersome ethical and legal requirements, laborious data management procedures, specific requirements for public data access, insufficient training and funding., Implications: We expect that experience gained in this project can be useful to improve data sharing; and that the datasets gathered can be used in future AMR projects., (Copyright © 2025. Published by Elsevier Ltd.)

Background: As COVID-19 is integrated into existing infectious disease control programs, it is important to understand the comparative clinical impact of COVID-19 and other respiratory diseases., Methods: We conducted a retrospective cohort study of patients with symptomatic healthcare-associated COVID-19 or influenza reported to the nationwide, hospital-based surveillance system in Switzerland. Included patients were adults (≥18 years) hospitalized for ≥3 days in tertiary care and large regional hospitals. Patients had COVID-19 symptoms and a RT-PCR-confirmed SARS-CoV-2 infection ≥3 days after hospital admission between 1 February 2022 and 30 April 2023, or influenza symptoms and a RT-PCR-confirmed influenza A or B infection ≥3 days after hospital admission between 1 November 2018 and 30 April 2023. Primary and secondary outcomes were 30-day in-hospital mortality and admission to intensive care unit (ICU), respectively. Cox regression (Fine-Gray model) was used to account for time-dependency and competing events, with inverse probability weighting to adjust for confounding., Results: We included 2901 patients with symptomatic healthcare-associated COVID-19 (Omicron) and 868 patients with symptomatic healthcare-associated influenza from nine hospitals. We found a similar case fatality ratio between healthcare-associated COVID-19 (Omicron) (6.2%) and healthcare-associated influenza (6.1%) patients; after adjustment, patients had a comparable subdistribution hazard ratio for 30-day in-hospital mortality (0.91, 95%CI 0.67-1.24). A similar proportion of patients were admitted to ICU (2.4% COVID-19; 2.6% influenza)., Conclusions: COVID-19 and influenza continue to cause severe disease among hospitalized patients. Our results suggest that in-hospital mortality risk of healthcare-associated COVID-19 (Omicron) and healthcare-associated influenza are comparable., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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 β-lactam/β-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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Each year, an estimated 7·7 million deaths are attributed to bacterial infections, of which 4.95 million are associated with drug-resistant pathogens, and 1·27 million are caused by bacterial pathogens resistant to the antibiotics available. Access to effective antibiotics when indicated prolongs life, reduces disability, reduces health-care expenses, and enables access to other life-saving medical innovations. Antimicrobial resistance undoes these benefits and is a major barrier to attainment of the Sustainable Development Goals, including targets for newborn survival, progress on healthy ageing, and alleviation of poverty. Adverse consequences from antimicrobial resistance are seen across the human life course in both health-care-associated and community-associated infections, as well as in animals and the food chain. The small set of effective antibiotics has narrowed, especially in resource-poor settings, and people who are very young, very old, and severely ill are particularly susceptible to resistant infections. This paper, the first in a Series on the challenge of antimicrobial resistance, considers the global scope of the problem and how it should be measured. Robust and actionable data are needed to drive changes and inform effective interventions to contain resistance. Surveillance must cover all geographical regions, minimise biases towards hospital-derived data, and include non-human niches., Competing Interests: Declaration of interests A meeting held to coordinate this paper was supported by the Bill & Melinda Gates Foundation (BMGF; INV-055356 to RL) and the Africa Centres for Disease Control and Prevention (to all authors). Neither funder had any role in the design, writing, or decision to submit this paper for publication. RL has received grant funding from the US National Science Foundation (CCF1918628). INO is a Calestous Juma Science Leadership fellow supported by BMGF (INV-036234, as well as INV-067684, INV-048135, and OPP1210746); receives grant funding from the UK National Institute for Health and Care Research (project number NIHR133307), Wellcome Trust, Public Health Alliance for Genomic Epidemiology, SEQAFRICA, Grand Challenges Africa Award (GCA/DD/rnd3/021), and International Vaccine Institute Award; receives royalties from Oxford University Press, Cornell University Press, and Springer; receives consulting fees from the Wellcome Trust; has received payment for lectures from the UK Microbiology Society; received travel support from BMGF, the European Society for Clinical Microbiology and Infectious Disease, and the American Society for Microbiology; has or had paid leadership roles in BMGF's surveillance advisory group (2019–21), the Thomas Bassir Biomedical Foundation Nigeria (2019 to present), and The International Centre for Antimicrobial Resistance Solutions Technical Advisory Forum (2021 to present); and has other unpaid positions in the African Journal of Laboratory Medicine, Microbial Genomics, The Lancet Infectious Diseases, Nigeria Center for Disease Control, and the Lancet Commission for Nigeria. SB is a member of staff at WHO; the views presented in this Series paper are those of the authors and do not reflect those of WHO. ACG receives consulting fees from Aché, Eurofarma, and União Química; receives payment for lectures from bioMérieux, Eurofarma, MSD, Pfizer, and Sandoz; received travel support from MSD and Pfizer; participates on the data monitoring board of Aché, Eurofarma, Hypera Pharma, MSD, Pfizer, Roche, Sandoz, United Medical, União, and Química; is a member of the Scientific Advisory Committee of the Global Antibiotic Research and Development Partnership (GARDP), the Health 1 Area Coordination board, and Fundação de Amparo à Pesquisa do Estado de São Paulo; and is a researcher for the Brazilian National Council for Scientific and Technological Development. MS receives funding from the Wellcome Trust (222051/Z/20/Z), GARDP, and EDCTP (NeoSep1); has unpaid leadership positions on the WHO Essential Medicine List Antibiotics Working Group and GARDP; and has been the Chief Investigator of clinical trials in children, where generic antibiotics have been donated by Sandoz, InfectoPharm, and Shionogi. All other authors report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Significant variations in the variables collected in clinical studies focusing on bacteraemia lead to inconsistency in the evaluation of risk factors for mortality., Objective: We aimed to define a minimum set of risk factors that should be assessed and reported in all studies assessing survival in bacteraemia., Study Eligibility: We conducted a systematic review including observational prospective and retrospective cohort studies that assessed all-cause mortality among patients with bacteraemia. We included only studies computing an adjusted analysis for mortality, with >500 participants., Exposures: Independently significant risk factors for all-cause, preferably 30-day, mortality., Data Sources: PubMed was used to identify eligible studies published between 2000 and 2020. A Delphi survey among experts was used to evaluate and prioritize the factors identified by the systematic review., Risk of Bias: SIGN checklist complemented by risk of bias assessment of the adjusted analysis., Data Synthesis: Definite universal risk factors were defined as those assessed in >50% of all included studies and significant in >50% of those. Potential universal risk factors were defined as those significant in >50% of studies evaluating the factor and a subgroup analysis was performed for studies of Staphylococcus aureus bacteraemia., Results: We included in the systematic review 62 studies, comprising more than 300,000 patients, from which a list of 17 risk factors was derived, whose association with all-cause mortality was statistically significant in most studies. The factors address baseline patient variables, the setting of infection acquisition, factors associated with the specific infection, the inflammatory response at onset of sepsis and management parameters where relevant. There were 14 risk factors for S. aureus bacteraemia., Conclusion: We identified a minimum set of universal factors to be collected, reported, and assessed, in all future studies evaluating factors associated with mortality in bacteraemia to improve study quality and harmonization., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children., Methods: We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0-18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I 2 statistic. The protocol was registered with PROSPERO (CRD42021260157)., Findings: After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%-55%; I 2 : 85.7%, number of isolates (n): 1032) and 84.9% (72.8%-92.2%; I 2 : 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%-97.9%; I 2 : 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%-56.5%; I 2 : 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%-86.3%; I 2 : 91.6%, n: 1886)., Interpretation: High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes., Funding: No funding was received., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

Background: Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action., Objectives: Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe., Methods: A systematic review and Bayesian meta-analysis., Data Sources: MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022., Study Eligibility Criteria: Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium, and patients with drug-susceptible or no infection., Participants: All patients diagnosed with drug-resistant bloodstream infections (BSIs)., Interventions: NA., Assessment of Risk of Bias: An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks., Methods of Data Synthesis: Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates., Results: Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], -0.72 to 4.17) and 1.78 (95% CrI, -0.02 to 3.38) days, respectively., Conclusions: Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined., Objectives: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe., Methods: A systematic review and meta-analysis., Data Sources: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022., Study Eligibility Criteria: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries., Participants: Paediatric and adult patients diagnosed with drug-resistant BSI., Interventions: Not applicable., Assessment of Risk of Bias: An adapted version of the Joanna-Briggs Institute assessment tool., Methods of Data Synthesis: Random-effect models were used to pool pathogen-specific burden estimates., Results: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively)., Conclusions: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 post-discharge 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 < 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 < 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 < 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., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Studies suggest that central venous catheter bloodstream infections (BSIs) increased during the COVID-19 pandemic. We investigated catheter-related BSIs in Switzerland and found peripheral venous catheter (PVC) BSI incidence increased during 2021-2022 compared with 2020. These findings should raise awareness of PVC-associated BSIs and prompt inclusion of PVC BSIs in surveillance systems.

Background: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa., Methods: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts., Findings: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts., Interpretation: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests JAGS declares research grants (paid to their institution) from the Wellcome Trust; UK Medical Research Council; UK National Institute for Health and Care Research; UK Foreign, Commonwealth & Development Office; Bill & Melinda Gates Foundation; and the EU. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Marlieke de Kraker discusses a systematic review and meta-analysis reporting the magnitude and consequences of bloodstream infections in low- and middle-income countries., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MdK receives funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 101034420 (PrIMAVeRa). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The author has been involved in the MBIRA study, the BALANCE study, and has contributed to the World Health Organization AMR attributable mortality protocol. Disclaimer: This communication reflects the author’s view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein., (Copyright: © 2023 Marlieke E. A. de Kraker. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: World Health Organization guidelines recommend administering surgical antimicrobial prophylaxis (SAP), including cefuroxime, within 120 minutes prior to incision. However, data from clinical settings supporting this long interval is limited., Objective: To assess whether earlier vs later timing of administration of cefuroxime SAP is associated with the occurrence of surgical site infections (SSI)., Design, Setting, and Participants: This cohort study included adult patients who underwent 1 of 11 major surgical procedures with cefuroxime SAP, documented by the Swissnoso SSI surveillance system between January 2009 and December 2020 at 158 Swiss hospitals. Data were analyzed from January 2021 to April 2023., Exposures: Timing of cefuroxime SAP administration before incision was divided into 3 groups: 61 to 120 minutes before incision, 31 to 60 minutes before incision, and 0 to 30 minutes before incision. In addition, a subgroup analysis was performed with time windows of 30 to 55 minutes and 10 to 25 minutes as a surrogate marker for administration in the preoperating room vs in the operating room, respectively. The timing of SAP administration was defined as the start of the infusion obtained from the anesthesia protocol., Main Outcomes and Measures: Occurrence of SSI according to Centers for Disease Control and Prevention definitions. Mixed-effects logistic regression models adjusted for institutional, patient, and perioperative variables were applied., Results: Of 538 967 surveilled patients, 222 439 (104 047 men [46.8%]; median [IQR] age, 65.7 [53.9-74.2] years), fulfilled inclusion criteria. SSI was identified in 5355 patients (2.4%). Cefuroxime SAP was administered 61 to 120 minutes prior to incision in 27 207 patients (12.2%), 31 to 60 minutes prior to incision in 118 004 patients (53.1%), and 0 to 30 minutes prior to incision in 77 228 patients (34.7%). SAP administration at 0 to 30 minutes was significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.85; 95% CI, 0.78-0.93; P < .001), as was SAP administration 31 to 60 minutes prior to incision (aOR, 0.91; 95% CI, 0.84-0.98; P = .01) compared with administration 61 to 120 minutes prior to incision. Administration 10 to 25 minutes prior to incision in 45 448 patients (20.4%) was significantly associated with a lower SSI rate (aOR, 0.89; 95% CI, 0.82-0.97; P = .009) vs administration within 30 to 55 minutes prior to incision in 117 348 patients (52.8%)., Conclusions and Relevance: In this cohort study, administration of cefuroxime SAP closer to the incision time was associated with significantly lower odds of SSI, suggesting that cefuroxime SAP should be administrated within 60 minutes prior to incision, and ideally within 10 to 25 minutes.

Objectives: We aimed to assess the association between carbapenem-resistant Enterobacterales (CRE) colonization pressure and carbapenem exposure and acquisition of carbapenemase-producing Enterobacterales (CPE) and non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE)., Methods: We conducted a parallel 1:2 matched case-control study at Rambam Health Care Campus, Israel, from January 2014 to June 2017. The cases included all adults who acquired CPE or non-CP-CRE in hospital. The controls were hospitalized patients who were negative for CRE on screening and matched by age, hospitalization division and the number of hospitalization days 90 days prior to CRE screening. The exposures of interest were high CRE colonization pressure, defined as a higher-than-median proportion of CRE carriers in the concurrent patient's department before acquisition, and carbapenem exposure, assessed as days of treatment. Conditional logistic regression was used for analyses of CPE and non-CP-CRE., Results: In total, 1058 patients were included: 278 CPE and 75 non-CP-CRE cases, matched to 556 and 149 controls, respectively. High CRE colonization pressure was associated with CPE acquisition (adjusted odds ratio [aOR], 2.6; 95% CI, 1.69-4.02); however, the duration of carbapenem treatment was not (aOR, 1.004; 95% CI, 0.98-1.03; 1-day increment). The duration of carbapenem treatment was significantly associated with non-CP-CRE acquisition (aOR per day, 1.07; 95% CI, 1.03-1.11). A source patient was identified significantly more frequently in epidemiological acquisition investigations of CPE than in those of non-CP-CRE (107/240, 44.6% vs. 18/64, 28.1%, respectively; p 0.017)., Conclusions: CPE acquisition was associated with horizontal transmission, whereas non-CP-CRE was associated with carbapenem exposure. Differences in the drivers of acquisition mandate tailored infection prevention efforts., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Secondary bacterial pneumonia is an important complication of seasonal influenza, but little data is available about impact on death and risk factors. This study identified risk factors for all-cause in-hospital mortality and secondary bacterial pneumonia among hospitalized adult patients with community-acquired influenza., Methods: A retrospective cohort study was performed at a tertiary teaching hospital in southwest China. The study cohort included all adult hospitalized patients with a laboratory-confirmed, community-acquired influenza virus infection during three consecutive influenza seasons from 2017 to 2020. Cause-specific Cox regression was used to analyze risk factors for mortality and secondary bacterial pneumonia, respectively, accounting for competing events (discharge alive and discharge alive or death without secondary bacterial pneumonia, respectively)., Results: Among 174 patients enrolled in this study, 14.4% developed secondary bacterial pneumonia and 11.5% died during hospitalization. For all-cause in-hospital mortality, time-varying secondary bacterial pneumonia was a direct risk factor of death (cause-specific hazard ratio [csHR] 3.38, 95% confidence interval [CI] 1.25-9.17); underlying disease indirectly increased death risk through decreasing the hazard of being discharged alive (csHR 0.55, 95% CI 0.39-0.77). For secondary bacterial pneumonia, the final model only confirmed direct risk factors: age ≥ 65 years (csHR 2.90, 95% CI 1.27-6.62), male gender (csHR 3.78, 95% CI 1.12-12.84) and mechanical ventilation on admission (csHR 2.96, 95% CI 1.32-6.64)., Conclusions: Secondary bacterial pneumonia was a major risk factor for in-hospital mortality among adult hospitalized patients with community-acquired influenza. Prevention strategies for secondary bacterial pneumonia should target elderly male patients and critically ill patients under mechanical ventilation., (© 2023. The Author(s).)

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; <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 colonization, urinary catheter and exposure to broad spectrum antibiotics., Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE)., Competing Interests: George L. Daikos reports personal fees from Pfizer, personal fees from MSD, outside the submitted work. Lionel K. Tan is an employee of and holds stocks and shares in GlaxoSmithKline. Pierluigi Viale reports grants from Shionogi and Gilead; personal fees from Shionogi, MSD, Allianz, Nordic, InfectoPharm, MundiPharm and Angelini, outside the submitted work. Jose María Reguera reports non-financial support from Pfizer. Lucía Valiente de Santis reports non-financial support from Pfizer. Julián Torre-Cisneros reports personal fees from MSD, Pfizer, Menarini, and Shionogi; and non-financial support from Pfizer, Shionogi and Gilead, outside the submitted work. Ángela Cano reports personal fees from Shionogi. Emmanuel Roilides reports personal fees from Amplyx, Astellas, Gilead, MSD, Pfizer, Scynexis, GSK and Shionogi, outside the submitted work. Marc J. Bonten reports grants paid to his institution from Janssen Vaccines, Novartis, CureVac and Merck; participation in Advisory Boards with payment to his institution from Spherecydes, Pfizer, Merck and Astra-Zeneca, and participation in Data Safety Monitoring Boards with payment to his institution from Sanofi. All other authors have no conflicts to declare., (© 2023 The Author(s).)

Importance: With the ongoing COVID-19 pandemic, it is crucial to assess the current burden of disease of community-acquired SARS-CoV-2 Omicron variant in hospitalized patients to tailor appropriate public health policies. Comparisons with better-known seasonal influenza infections may facilitate such decisions., Objective: To compare the in-hospital outcomes of patients hospitalized with the SARS-CoV-2 Omicron variant with patients with influenza., Design, Setting, and Participants: This cohort study was based on a national COVID-19 and influenza registry. Hospitalized patients aged 18 years and older with community-acquired SARS-CoV-2 Omicron variant infection who were admitted between January 15 and March 15, 2022 (when B.1.1.529 Omicron predominance was >95%), and hospitalized patients with influenza A or B infection from January 1, 2018, to March 15, 2022, where included. Patients without a study outcome by August 30, 2022, were censored. The study was conducted at 15 hospitals in Switzerland., Exposures: Community-acquired SARS-CoV-2 Omicron variant vs community-acquired seasonal influenza A or B., Main Outcomes and Measures: Primary and secondary outcomes were defined as in-hospital mortality and admission to the intensive care unit (ICU) for patients with the SARS-CoV-2 Omicron variant or influenza. Cox regression (cause-specific and Fine-Gray subdistribution hazard models) was used to account for time-dependency and competing events, with inverse probability weighting to adjust for confounders with right-censoring at day 30., Results: Of 5212 patients included from 15 hospitals, 3066 (58.8%) had SARS-CoV-2 Omicron variant infection in 14 centers and 2146 patients (41.2%) had influenza A or B in 14 centers. Of patients with the SARS-CoV-2 Omicron variant, 1485 (48.4%) were female, while 1113 patients with influenza (51.9%) were female (P = .02). Patients with the SARS-CoV-2 Omicron variant were younger (median [IQR] age, 71 [53-82] years) than those with influenza (median [IQR] age, 74 [59-83] years; P < .001). Overall, 214 patients with the SARS-CoV-2 Omicron variant (7.0%) died during hospitalization vs 95 patients with influenza (4.4%; P < .001). The final adjusted subdistribution hazard ratio (sdHR) for in-hospital death for SARS-CoV-2 Omicron variant vs influenza was 1.54 (95% CI, 1.18-2.01; P = .002). Overall, 250 patients with the SARS-CoV-2 Omicron variant (8.6%) vs 169 patients with influenza (8.3%) were admitted to the ICU (P = .79). After adjustment, the SARS-CoV-2 Omicron variant was not significantly associated with increased ICU admission vs influenza (sdHR, 1.08; 95% CI, 0.88-1.32; P = .50)., Conclusions and Relevance: The data from this prospective, multicenter cohort study suggest a significantly increased risk of in-hospital mortality for patients with the SARS-CoV-2 Omicron variant vs those with influenza, while ICU admission rates were similar.

Introduction: Little is known about the bloodstream infection (BSI) risk associated with short-term peripheral venous catheters (PVCs) and no large study investigated the insertion site-related risk for PVC-BSI., Methods: We performed a cohort study at the University of Geneva Hospitals using the prospective hospital-wide BSI surveillance database. We analyzed the association between insertion site and risk of PVC-BSI on the upper extremity using univariable and multivariable marginal Cox models., Results: Between 2016 and 2020, utilization of 403'206 peripheral venous catheters were prospectively recorded in a 2000-bed hospital consortium with ten sites. Twenty-seven percent of PVC (n = 109'686) were inserted in the hand. After adjustment for confounding factors, hand insertion was associated with a decreased PVC-BSI risk (adjusted hazard ratio [HR] 0.42, 95% CI 0.18-0.98, p = 0.046) compared to more proximal insertion sites. In a sensitivity analysis for PVCs with ≥ 3 days of dwell time, we confirmed a decreased PVC-BSI risk after hand insertion (HR 0.37, 95% CI 0.15-0.93, p = 0.035)., Conclusion: Hand insertion should be considered for reducing PVC infections, especially for catheters with an expected dwell time of more than 2 days., (© 2022. The Author(s).)

Background: Hand hygiene is at the core of effective infection prevention and control (IPC) programmes. 10 years after the development of the WHO Multimodal Hand Hygiene Improvement Strategy, we aimed to ascertain the level of hand hygiene implementation and its drivers in health-care facilities through a global WHO survey., Methods: From Jan 16 to Dec 31, 2019, IPC professionals were invited through email and campaigns to complete the online Hand Hygiene Self-Assessment Framework (HHSAF). A geospatial clustering algorithm selected unique health-care facilities responses and post-stratification weighting was applied to improve representativeness. Weighted median HHSAF scores and IQR were reported. Drivers of the HHSAF score were determined through a generalised estimation equation., Findings: 3206 unique responses from 90 countries (46% WHO Member States) were included. The HHSAF score indicated an intermediate hand hygiene implementation level (350 points, IQR 248-430), which was positively associated with country income level and health-care facility funding structure. System Change had the highest score (85 points, IQR 55-100), whereby alcohol-based hand rub at the point of care has become standard practice in many health-care facilities, especially in high-income countries. Institutional Safety Climate had the lowest score (55 points, IQR 35-75). From 2015 to 2019, the median HHSAF score in health-care facilities participating in both HHSAF surveys (n=190) stagnated., Interpretation: Most health-care facilities had an intermediate level of hand hygiene implementation or higher, for which health-care facility funding and country income level were important drivers. Availability of resources, leadership, and organisational support are key elements to further improve quality of care and provide access to safe care for all., Funding: WHO, Geneva University Hospitals and Faculty of Medicine, and WHO Collaborating Center on Patient Safety, Geneva, Switzerland., Competing Interests: Declaration of interests All authors declare no competing interests., (© 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: WHO core components for infection prevention and control (IPC) are important building blocks for effective IPC programmes. To our knowledge, we did the first WHO global survey to assess implementation of these programmes in health-care facilities., Methods: In this cross-sectional survey, IPC professionals were invited through global outreach and national coordinated efforts to complete the online WHO IPC assessment framework (IPCAF). The survey was created in English and was then translated into ten languages: Arabic, Chinese, English, French, German, Italian, Japanese, Russian, Spanish, and Thai. Post-stratification weighting was applied and countries with low response rates were excluded to improve representativeness. Weighted median scores and IQRs as well as weighted proportions (Nw) meeting defined IPCAF minimum requirements were reported. Indicators associated with the IPCAF score were assessed using a generalised estimating equation., Findings: From Jan 16 to Dec 31, 2019, 4440 responses were received from 81 countries. The overall weighted IPCAF median score indicated an advanced level of implementation (605, IQR 450·4-705·0), but significantly lower scores were found in low-income (385, 279·7-442·9) and lower-middle-income countries (500·4, 345·0-657·5), and public facilities (515, 385-637·8). Core component 8 (built environment; 90·0, IQR 75·0-100·0) and core component 2 (guidelines; 87·5, 70·0-97·5) scored the highest, and core component 7 (workload, staffing, and bed occupancy; 70·0, 50-90) and core component 3 (education and training; 70 ·0, 50·0-85·0) scored the lowest. Overall, only 15·2% (Nw: 588 of 3873) of facilities met all IPCAF minimum requirements, ranging from 0% (0 of 417) in low-income countries to 25·6% (278 of 1087) in primary facilities, 9% (24 of 268) in secondary facilities, and 19% (18 of 95) in tertiary facilities in high-income countries., Interpretation: Despite an overall high IPCAF score globally, important gaps in IPC facility implementation and core components across income levels hinder IPC progress. Increased support for more effective and sustainable IPC programmes is crucial to reduce risks posed by outbreaks to global health security and to ensure patient and health worker safety., Funding: WHO and the Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine., Translations: For the French and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (© 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: Enterobacteriaceae are common pathogens causing bloodstream infection (BSI) in sub-Saharan Africa and frequently express third-generation cephalosporin (3GC) resistance; however, the impact of 3GC resistance on clinical outcomes is rarely studied., Methods: We conducted a single-site prospective cohort study at Tygerberg Hospital, Cape Town, South Africa to examine the feasibility of measuring impacts of 3GC resistance in Enterobacteriaceae BSI. We included patients with 3GC-susceptible and 3GC-resistant BSIs and matched each BSI patient to two uninfected patients. We determined the concordance of initial antibiotic treatment with the corresponding isolate's susceptibility profile. We performed exploratory impact analysis using multivariable regression models., Results: Between 1 June 2017 and 31 January 2018, we matched 177 Enterobacteriaceae BSI patients to 347 uninfected patients. Among these BSIs, 35% were phenotypically 3GC resistant. Parameters describing clinical comorbidity showed strong associations with mortality. We found that 18% of 3GC-R and 3% of 3GC-S BSI patient received non-concordant initial therapy. In multivariable Cox regression, we found a mortality impact over their matched patients for both 3GC-R (cause-specific hazard ratio 23.77; 95% CI 5.12-110.3) and 3GC-S (HR 7.49; 95%CI 3.08-18.19) BSI. There was a nonsignificant ratio of these ratios (HR 3.18; 95% CI 0.54-18.70), limited by the small sample size., Conclusion: This form of impact estimation was feasible in one hospital in South Africa where 3GC-R status was associated with non-concordant initial antibiotic treatment. There was a possible increase in mortality among individuals with 3GC-resistant Enterobacteriaceae, but with broad confidence intervals. These analytical approaches could be applied to larger datasets to improve precision of estimates., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The increased focus on the public health burden of antimicrobial resistance (AMR) raises conceptual challenges, such as determining how much harm multidrug-resistant organisms do compared to what, or how to establish the burden. Here, we present a counterfactual framework and provide guidance to harmonize methodologies and optimize study quality. In AMR-burden studies, 2 counterfactual approaches have been applied: the harm of drug-resistant infections relative to the harm of the same drug-susceptible infections (the susceptible-infection counterfactual); and the total harm of drug-resistant infections relative to a situation where such infections were prevented (the no-infection counterfactual). We propose to use an intervention-based causal approach to determine the most appropriate counterfactual. We show that intervention scenarios, species of interest, and types of infections influence the choice of counterfactual. We recommend using purpose-designed cohort studies to apply this counterfactual framework, whereby the selection of cohorts (patients with drug-resistant, drug-susceptible infections, and those with no infection) should be based on matching on time to infection through exposure density sampling to avoid biased estimates. Application of survival methods is preferred, considering competing events. We conclude by advocating estimation of the burden of AMR by using the no-infection and susceptible-infection counterfactuals. The resulting numbers will provide policy-relevant information about the upper and lower bound of future interventions designed to control AMR. The counterfactuals should be applied in cohort studies, whereby selection of the unexposed cohorts should be based on exposure density sampling, applying methods avoiding time-dependent bias and confounding., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

BackgroundSince the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data.AimThis study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.MethodsThis retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders.ResultsIn 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54-78) than the patients with influenza (median 74 years; IQR: 61-84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22-4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00-3.00, p < 0.001) for ICU admission.ConclusionCommunity-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.

Background: Evidence about the impact of the pandemic of COVID-19 on the incidence rates of blood cultures contaminations and bloodstream infections in intensive care units (ICUs) remains scant. The objective of this study was to investigate the nationwide epidemiology of positive blood cultures drawn in ICUs during the first two pandemic waves of COVID-19 in Switzerland., Methods: We analyzed data on positive blood cultures among ICU patients, prospectively collected through a nationwide surveillance system (ANRESIS), from March 30, 2020, to May 31, 2021, a 14-month timeframe that included a first wave of COVID-19, which affected the French and Italian-speaking regions, an interim period (summer 2020) and a second wave that affected the entire country. We used the number of ICU patient-days provided by the Swiss Federal Office of Public Health as denominator to calculate incidence rates of blood culture contaminations and bloodstream infections (ICU-BSI). Incidence rate ratios comparing the interim period with the second wave were determined by segmented Poisson regression models., Results: A total of 1099 blood culture contaminations and 1616 ICU-BSIs were identified in 52 ICUs during the study. Overall, more episodes of blood culture contaminations and ICU-BSI were observed during the pandemic waves, compared to the interim period. The proportions of blood culture contaminations and ICU-BSI were positively associated with the ICU occupancy rate, which was higher during the COVID-19 waves. During the more representative second wave (versus interim period), we observed an increased incidence of blood culture contaminations (IRR 1.57, 95% CI 1.16-2.12) and ICU-BSI (IRR 1.20, 95% CI 1.03-1.39)., Conclusions: An increase in blood culture contaminations and ICU-BSIs was observed during the second COVID-19 pandemic wave, especially in months when the ICU burden of COVID-19 patients was high., (© 2021. The Author(s).)

Importance: Peripheral intravenous catheters (PVCs) are the most frequently used indwelling devices in hospitals worldwide. Peripheral intravenous catheter bloodstream infections (PVC-BSIs) are rare, but severe and preventable, adverse events., Objective: To investigate the incidence of PVC-BSIs after changing the policy of routine PVC replacement every 96 hours to clinically indicated replacement., Design, Setting, and Participants: This institution-wide, observational cohort study evaluated all patients hospitalized at a large university-affiliated hospital with 10 sites in Western Switzerland with a PVC insertion between January 1, 2016, and February 29, 2020., Exposures: Peripheral intravenous catheters were routinely replaced every 96 hours until March 31, 2018 (baseline period). Between April 1, 2018, and October 15, 2019, PVCs were replaced if clinically indicated (intervention period). From October 16, 2019, PVCs were again routinely replaced every 96 hours (reversion period)., Main Outcomes and Measures: The PVC-BSI rates and PVC-BSI incidence rate ratios (IRRs) during each period., Results: A total of 412 631 PVCs with documented catheter duration were included (164 331 patients; median [interquartile range] patient age, 51 [33-72] years; 88 928 [54.1%] female): 241 432 PVCs at baseline, 130 779 at intervention, and 40 420 at reversion. Eleven PVC-BSIs were observed during the baseline period, 46 during the intervention, and 4 during the reversion period. Although the monthly number of PVC-days remained stable during all study periods, the number of monthly inserted PVCs decreased during the intervention period. The number of PVCs still in place more than 4 or more than 7 days was higher during the intervention period compared with the baseline and reversion periods. A significantly increased IRR of PVC-BSIs was observed for the intervention period (IRR, 7.20; 95% CI, 3.65-14.22; P < .001) compared with baseline, whereas during the reversion period there was no significant increase (IRR, 1.35; 95% CI, 0.30 6.17; P = .69)., Conclusions and Relevance: The results of this cohort study using a large, prospective surveillance database suggest that replacement of PVCs only when clinically indicated may be associated with an increased risk of PVC-BSI compared with routine replacement. Even if PVC-associated BSI is a rare event, the use of PVCs in most patients makes this outcome relevant.

Objectives: The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Surveillance and Quality Assessment Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control., Methods: From October to December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire, including Likert scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed and free-text questions were thematically analysed., Results: Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; P < 0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (P < 0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased ICU admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antimicrobial prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19., Conclusions: This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses highlight important actions to help ensure that AMR remains a global health priority, including engaging with GLASS to facilitate reliable AMR surveillance data, seizing the opportunity to develop more sustainable IPC programmes, promoting integrated antibiotic stewardship guidance, leveraging increased laboratory capabilities and other system-strengthening efforts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objectives: This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient., Methods: Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis., Results: We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3-14.1)., Conclusions: ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings., Clinical Study Registration: German Clinical Trials Register, DRKS-ID: DRKS00013250., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

As with any health threat, our ability to respond to the emergence and spread of antimicrobial resistance depends on our ability to understand the scale of the problem, magnitude, geographical spread, and trends over time. This is especially true for resistance emergence to newer antibiotics coming to the market as last-resort treatments. Yet current antibiotic surveillance systems are limited to monitoring resistance to commonly prescribed drugs that have been on the market for a long time. This qualitative study determined the essential elements and requirements of antimicrobial resistance surveillance for new antibiotics based on literature review, interviews and expert consensus. After an extensive mapping exercise, 10 experts participated in a modified Delphi consultation to identify consensus on all elements required for surveillance of resistance to novel antibiotics. The main findings indicate that there is a need for a two-phase system; an early alert system transitioning to routine surveillance, led by the public sector to gather and share essential data on resistance to newer antibiotics in a transparent manner. The system should be decentralized, run largely from national level, but be coordinated by an arm of an existing international public health institution. Priority should be given to monitoring emergence of resistance among already multi-drug resistant pathogens causing infections, over a broader selection of pathogens to maximize clinical impact. In conclusion, we cannot rely on current AMR surveillance systems to monitor resistance emergence to new antibiotics. A new, public system should be set-up, starting with a focus on detecting resistance emergence, but expanding to a more comprehensive surveillance as soon as there is regional spread of resistance to the new antibiotic. This article provides a framework based on expert agreement, which could guide future initiatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morel, de Kraker, Harbarth and The Enhanced Surveillance Expert Consensus Group (CANSORT-SCI).)

Objectives/purpose: The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level., Methods: GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level., Results: The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies., Conclusion: In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats.

The scarcity of novel antibiotic compounds in a time of increasing resistance rates has begun to ring alarm bells at the highest echelons of government. Large new financial incentives to accelerate antibiotic research and development, such as market entry rewards (MERs), are being considered. However, there is little focus on how to sustain the efficacy of new, promising antibiotics reaching the market. Currently, inappropriate use of antibiotics is commonplace, which has accelerated resistance development. In an attempt to halt this trend, antibiotic stewardship policies are being implemented in many resource-rich settings. Unfortunately, this has not yet had an impact on the amount of antibiotics being prescribed globally. One important hurdle is misalignment of incentives. While governments and health services are incentivized to promote prudent use of this common good, pharmaceutical companies are incentivized to increase volume of sales to maximize profits. This problem must be addressed or else the major efforts going into developing new antibiotics will be in vain. In this paper we outline an approach to realign the incentives of pharmaceutical companies with wider antibiotic conservation efforts by making a staged bonus a component of an MER for antibiotic developers when resistance to their drug remains low over time. This bonus could address the lack of stewardship focus in any innovation-geared incentive.

Objectives: The aim was to evaluate the effect of duration of therapy (DOT) on mortality and relapse for patients with Staphylococcus aureus bacteraemia (SAB)., Methods: We performed a retrospective single-centre cohort study including adult patients with SAB. We determined the association between DOT (≤14 days versus >14 days) and mortality by adjusted hazard ratios (aHR) and 95% confidence intervals through Cox regression adjusted for immortal-time bias and confounding by indication, stratified by presence of complicated SAB (any of: endocarditis, implant, duration of SAB >2 days, fever >3 days). The primary outcome was 90-day all-cause mortality, and the secondary outcome was 90-day relapse., Results: Between January 2010 and December 2015, we included 530 patients, of whom 94 out of 530 (17.7%) had methicillin-resistant SAB and 305 out of 530 (57.6%) had complicated SAB. Ninety-day mortality was 27.0% (143/530), with no significant trend across the study period; median time to death was 17 days (interquartile range (IQR) 8-30) after onset of SAB. Median DOT was 20 days (IQR 13-39). Patients with complicated SAB had significantly reduced mortality with DOT >14 days (aHR 0.32, 95% CI 0.16-0.64). DOT was not associated with mortality in patients with uncomplicated SAB (aHR 0.85; 0.41-1.78). Eighteen (18/530) patients (3.4%) relapsed; on univariate analysis, DOT was not associated with relapse (HR 1.01; 0.97-1.06)., Conclusions: DOT >14 days is associated with higher survival in patients with complicated SAB, but not for patients with uncomplicated SAB. No association was found for relapse, but 90-day relapse was very low in this cohort. Importantly, 90-day mortality remained high across the study period., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Hand hygiene is crucial in infection prevention and control. It is unclear whether sprayed alcohol-based hand rub (ABHR) is non-inferior to the World Health Organization (WHO)-recommended method of handrubbing with poured ABHR., Aim: To test whether sprayed ABHR can be an alternative (non-inferior) method for effective hand hygiene with/without handrubbing., Methods: A laboratory experiment was conducted with ABHR (isopropanol 60% v/v) according to European Norm 1500. Hand hygiene was performed by: (1) handrubbing with ABHR poured on to the palm of the hand; (2) handrubbing with sprayed ABHR; and (3) applying sprayed ABHR to hands without handrubbing. Hands were contaminated with Escherichia coli ATCC 10536, followed by hand hygiene and microbiological sampling. A generalized linear mixed model with a random intercept per subject was used to analyse the reduction in bacterial count following hand hygiene., Findings: In total, 19 healthcare workers participated in the study. Handrubbing with sprayed ABHR was non-inferior [margin log 10 0.6 colony-forming units (cfu)/mL] to the WHO-recommended method of handrubbing with poured ABHR; bacterial count reductions were log 10 3.66 cfu/mL [95% confidence interval (CI) 1.68-5.64] and log 10 3.46 cfu/mL (95% CI 1.27-5.65), respectively. Conversely, non-inferiority was not found for sprayed ABHR without handrubbing [bacterial count reduction log 10 2.76 cfu/mL (95% CI 1.65-3.87)]., Conclusion: Handrubbing with sprayed ABHR was non-inferior to handrubbing with ABHR poured on to the palm of the hand to reduce bacterial counts on hands under experimental conditions. Handrubbing with sprayed ABHR may be an acceptable alternative hand hygiene method pending assessment in other settings and for other pathogens., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Compliance with the World Health Organization 'how to handrub' action is suboptimal. Simplifying the hand-hygiene action may improve practice. However, it is crucial to preserve antibacterial efficacy. We tested the non-inferiority of 15 versus 30 seconds handrubbing for Staphylococcus aureus and Escherichia coli contamination at different loads, using hand-size customized alcohol-based handrub (ABHR) volumes., Methods: In an EN1500-based study, 18 health-care workers (HCWs) with extensive experience in hand hygiene rubbed hands with a hand-size customized volume of isopropanol 60% v/v. They repeated the following sequence: hand contamination (E. coli or S. aureus; broth containing 10 8 or 10 6  CFU/mL); baseline fingertips sampling; handrubbing (15 or 30 seconds); re-sampling. The main outcome was log 10  CFU corrected reduction factor (cRF) on HCWs' hands, applying a generalized linear mixed model with a random intercept for subject., Results: The median cRF was 2.1 log 10 (interquartile range 1.50-3.10). After fitting the model, cRF was significantly higher for S. aureus compared with E. coli but there was no significant effect for duration of handrubbing or contamination fluid concentration. Fifteen seconds of handrubbing was non-inferior to 30 (-0.06 log 10 , 95% CI -0.34 to 0.22; EN1500 0.60 log 10 non-inferiority margin). This was confirmed in all pre-specified subgroups., Conclusion: Among experienced HCWs using a hand-size customized volume of ABHR, handrubbing for 15 seconds was non-inferior to 30 seconds in reducing bacterial load, irrespective of type of bacteria or contamination fluid concentration. This provides further support for a shorter, 15-seconds, hand-hygiene action., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Surveillance of surgical site infections (SSIs) is a core component of effective infection control practices, though its impact has not been quantified on a large scale., Aim: To determine the time-trend of SSI rates in surveillance networks., Methods: SSI surveillance networks provided procedure-specific data on numbers of SSIs and operations, stratified by hospitals' year of participation in the surveillance, to capture length of participation as an exposure. Pooled and procedure-specific random-effects Poisson regression was performed to obtain yearly rate ratios (RRs) with 95% confidence intervals (CIs), and including surveillance network as random intercept., Findings: Of 36 invited networks, 17 networks from 15 high-income countries across Asia, Australia and Europe participated in the study. Aggregated data on 17 surgical procedures (cardiovascular, digestive, gynaecological-obstetrical, neurosurgical, and orthopaedic) were collected, resulting in data concerning 5,831,737 operations and 113,166 SSIs. There was a significant decrease in overall SSI rates over surveillance time, resulting in a 35% reduction at the ninth (final) included year of surveillance (RR: 0.65; 95% CI: 0.63-0.67). There were large variations across procedure-specific trends, but strong consistent decreases were observed for colorectal surgery, herniorrhaphy, caesarean section, hip prosthesis, and knee prosthesis., Conclusion: In this large, international cohort study, pooled SSI rates were associated with a stable and sustainable decrease after joining an SSI surveillance network; a causal relationship is possible, although unproven. There was heterogeneity in procedure-specific trends. These findings support the pivotal role of surveillance in reducing infection rates and call for widespread implementation of hospital-based SSI surveillance in high-income countries., (Copyright © 2018 The Healthcare Infection Society. All rights reserved.)

Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical trials, which has resulted in 8 recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic modeling, emphasizing the pertinence of population-based pharmacokinetic models, regulatory procedures for the reassessment of old antibiotics, and rigorous quality improvement. Recommendations 4 and 5 address the need for more sensitive primary end points through the use of rank-based or time-dependent composite end points. Recommendation 6 relates to the applicability of hierarchical nested-trial designs, and the last 2 recommendations propose the incorporation of historical or concomitant trial data through Bayesian methods and/or platform trials. Although not all of these recommendations are directly applicable, they provide a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge.

We evaluated whether hand wiping is noninferior to hand rubbing in reducing the bacterial concentration on hands. In 20 healthy volunteers, hand wiping with or without an alcohol-based solution was inferior to hand rubbing with an alcohol-based solution. This finding warrants a note of caution for the application of wipes in health care. Infect Control Hosp Epidemiol 2018;39:332-335.

Aims: In this narrative review, we provide a framework for assessing the quality of evidence provided by studies investigating antimicrobial stewardship (AMS) interventions, and inform the design and planning stage for future AMS evaluation studies to determine the best strategies to keep antimicrobial resistance at bay., Sources: Cochrane/Pubmed., Content: As AMS is mostly applied in a complex, real-world setting, bias and random time effects can jeopardize the validity of causal inference. The most important risks include simultaneously implemented infection prevention strategies and regression to the mean. Inclusion of homogeneous intervention and control arms, through randomization of the intervention, can limit these risks. However, contamination can play an important role for AMS; therefore, randomization at cluster-level, instead of randomization at individual-level, is recommended. It can be challenging to identify enough representative clusters, and implementation of a cluster-RCT (cRCT) can be costly. Controlled interrupted time series (ITS) design has a high validity as well, and is relatively straightforward to implement, although time-varying confounding should be considered. Independent of the study design, it is crucial to include multiple process, clinical outcome, microbiological and financial measures, to be able to detect possible, unintended consequences., Implications: Future studies assessing the impact of new AMS strategies should produce compelling evidence by opting for cRCTs, or ITS including a control arm. Furthermore, a holistic view of intended and unintended consequences should be reported, and a detailed process evaluation should be provided to adequately inform implementation of successful AMS strategies to battle the rising burden of AMR., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: In this era of rising antimicrobial resistance, slowly refilling antibiotic development pipelines, and an aging population, we need to ensure that randomized clinical trials (RCTs) determine the added benefit of new antibiotic agents effectively and in a valid way, especially for severely ill patients. Unfortunately, universally accepted endpoints for the evaluation of new drugs in severe infections are lacking., Methods: We review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches., Results: Usual endpoints actually recommended for drug development suffer from important flaws. Mortality requires large sample size and only partly related to the infectious process. Clinical cure rate is highly subjective in critically ill patients where symptoms may be related to other intercurrent events. Currently, composite endpoints, hierarchical nested designs, and competing risks analysis seem to be the most promising new tools for designing and analyzing clinical trials in this area, although they require further validation., Conclusion: Regulatory authorities, pharmaceutical companies, and clinicians need to agree on the most appropriate clinical endpoints for severe infections to ensure efficient approval of new, effective antibiotic agents.