antibiotic resistance; bacteremia; bloodstream infection; hospital-acquired; Anti-Infective Agents; Carbapenems; Anti-Bacterial Agents; Adult; Humans; Cohort Studies; Prospective Studies; Intensive Care Units; Escherichia coli; Hospitals; Carbapenems/therapeutic use; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy; Cross Infection/prevention & control; Anti-Infective Agents/therapeutic use; Cross Infection; Critical Care and Intensive Care Medicine
Abstract :
[en] [en] PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials.
METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021.
RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28.
CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Tabah, Alexis ; Intensive Care Unit, Redcliffe Hospital, Brisbane, Australia. a.tabah@uq.edu.au ; Queensland Critical Care Research Network (QCCRN), Brisbane, QLD, Australia. a.tabah@uq.edu.au ; Queensland University of Technology, Brisbane, QLD, Australia. a.tabah@uq.edu.au ; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. a.tabah@uq.edu.au
Buetti, Niccolò; Infection Control Program and WHO Collaborating Centre on Patient Safety, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland ; Université de Paris, INSERM, IAME UMR 1137, 75018, Paris, France
Staiquly, Quentin; ICUREsearch, Biometry, 38600, Fontaine, France
Ruckly, Stéphane; Université de Paris, INSERM, IAME UMR 1137, 75018, Paris, France ; ICUREsearch, Biometry, 38600, Fontaine, France
Akova, Murat; Department of Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey
Aslan, Abdullah Tarik; Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
Leone, Marc; Department of Anesthesiology and Intensive Care Unit, Hospital Nord, Aix Marseille University, Assistance Publique Hôpitaux Universitaires de Marseille, Marseille, France
Conway Morris, Andrew ; Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK ; Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, Cb2 1QP, UK ; JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, Hills Road, Cambridge, CB2 0QQ, UK
Bassetti, Matteo; Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy
Arvaniti, Kostoula; Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloníki, Greece
Lipman, Jeffrey; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia ; Nimes University Hospital, University of Montpellier, Nimes, France ; Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Herston, Australia
Ferrer, Ricard; Intensive Care Department, SODIR-VHIR Research Group, Vall d'Hebron University Hospital, Barcelona, Spain
Qiu, Haibo; Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing, 210009, China
Paiva, José-Artur; Intensive Care Medicine Department, Centro Hospitalar Universitário Sao Joao, Porto, Portugal ; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal ; Infection and Sepsis ID Group, Porto, Portugal
Povoa, Pedro; NOVA Medical School, New University of Lisbon, Lisbon, Portugal ; Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Odense, Denmark ; Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, CHLO, Lisbon, Portugal
De Bus, Liesbet ; Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium
De Waele, Jan ; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium ; Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
Zand, Farid; Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Gurjar, Mohan ; Department of Critical Care Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India
Alsisi, Adel; ICU Department, Prime Hospital, Dubai, United Arab Emirates ; Critical Care Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Abidi, Khalid; Medical ICU, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
Bracht, Hendrik; Central Interdisciplinary Emergency Medicine, University Hospital Ulm, Ulm, Germany
Hayashi, Yoshiro; Department of Intensive Care Medicine, Kameda General Hospital, Kamogawa, Japan
Jeon, Kyeongman; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Elhadi, Muhammed; Faculty of Medicine, University of Tripoli, Tripoli, Libya
Barbier, François; Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional d'Orléans, 14, avenue de L'Hôpital, 45100, Orléans, France
Timsit, Jean-François; Université Paris-Cité, INSERM, IAME UMR 1137, 75018, Paris, France ; Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard University Hospital, 46 Omdurman maternity hospitalrue Henri Huchard, 75877, Paris Cedex, France
ESICM - European Society of Intensive Care Medicine ESCMID - European Society of Clinical Microbiology and Infectious Diseases Norva Dahlia Intensive Care Research Foundation Redcliffe Hospital
Funding text :
JdW is a senior clinical investigator funded by the Research Foundation Flanders (FWO, Ref. 1881020N). ACM is supported by a Medical Research Council Clinician Scientist Fellowship (MR/ V006118/1). NB received a fellowship grant (Grant number: P4P4PM_194449) from the Swiss National Science Foundation. Research grants were obtained from the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund.The EUROBACT-2 study was endorsed by the European Society of Intensive Care Medicine (ESICM), the infection section of the ESCIM and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), with scientific input of the OUTCOMEREA network. The members of the Eurobact 2 Study Group are: Alexis Tabah, Hamish Pollock, Ben Margetts, Meredith Young, Neeraj Bhadange, Steven Tyler, Anne Ledtischke, Mackenzie Finnis, Anne Ledtischke, Mackenzie Finnis, Jyotsna Dwivedi, Manoj Saxena, Vishwanath Biradar, Natalie Soar, Vineet Sarode, David Brewster, Adrian Regli, Elizabeth Weeda, Samiul Ahmed, Cheryl Fourie, Kevin Laupland, Mahesh Ramanan, James Walsham, Jason Meyer, Edward Litton, Anna Maria Palermo, Timothy Yap, Ege Eroglu, Antony George Attokaran, C'havala Jaramillo, Khalid Mahmood Khan Nafees, Nurhikmahtul Aqilah Haji Abd Rashid, Haji Adi Muhamad Ibnu Walid, Tomas Mon, P. Dhakshina Moorthi, Shah Sudhirchandra, Dhadappa Damodar Sridharan, Qiu Haibo, Xie Jianfeng, Lu Wei-Hua, Wang Zhen, Chuanyun Qian, Jili Luo, Xiaomei Chen, Hao Wang, Peng Zhao, Juan Zhao, Qiu Wusi, Chen Mingmin, Lei Xu, Chengfen Yin, Ruilan Wang, Jinfeng Wang, Yongjie Yin, Min Zhang, Jilu Ye, Chungfang Hu, Suming Zhou, Min Huang, Jing Yan, Yan Wang, Bingyu Qin, Ling Ye, Xie Weifeng, Li Peije, Nan Geng, Yoshiro Hayashi, Toshiyuki Karumai, Masaki Yamasaki, Satoru Hashimoto, Koji Hosokawa, Jun Makino, Takeo Matsuyoshi, Akira Kuriyama, Hidenobu Shigemitsu, Yuka Mishima, Michio Nagashima, Hideki Yoshida, Shigeki Fujitani, Koichiro Omori, Hiroshi Rinka, Hiroki Saito, Kaori Atobe, Hideaki Kato, Shunsuke Takaki, M. Shahnaz Hasan, Muhamad Fadhil Hadi Jamaluddin, Lee See Pheng, Sheshendrasurian Visvalingam, Mun Thing Liew, Siong Ling Danny Wong, Kean Khang Fong, Hamizah Bt Abdul Rahman, Zuraini Md Noor, Lee Kok Tong, Abd. Hamid Azman, Mohd Zulfakar Mazlan, Saedah Ali, Kyeongman Jeon, Sang-Min Lee, Sunghoon Park, Seung Yong Park, Sung Yoon Lim, Qing Yuan Goh, Shin Yi Ng, Sui An Lie, Andrea Lay Hoon Kwa, Ken Junyang Goh, Andrew Yunkai Li, Caroline Yu Ming Ong, Jia Yan Lim, Jessica Lishan Quah, Kangqi Ng, Louis Xiang Long Ng, Yu Chang Yeh, Nai-Kuan Chou, Cong-Tat Cia, Ting-Yu Hu, Li-Kuo Kuo, Shih-Chi Ku, Phunsup Wongsurakiat, Yutthana Apichatbutr, Supattra Chiewroongroj, Rashid Nadeem, Ashraf El Houfi, Adel Alsisi, Amr Elhadidy, Mina Barsoum, Nermin Osman, Tarek Mostafa, Mohamed Elbahnasawy, Ahmed Saber, Amer Aldhalia, Omar Elmandouh, Ahmed Elsayed, Merihan A. Elbadawy, Ahmed K. Awad, Hanan M. Hemead, Farid Zand, Maryam Ouhadian, Seyed Hamid Borsi, Zahra Mehraban, Davood Kashipazha, Fatemeh Ahmadi, Mohsen Savaie, Farhad Soltani, Mahboobeh Rashidi, Reza Baghbanian, Fatemeh Javaherforoosh, Fereshteh Amiri, Arash Kiani, Mohammad Amin Zargar, Ata Mahmoodpoor, Fatemeh Aalinezhad, Gholamreza Dabiri, Golnar Sabetian, Hakimeh Sarshad, Mansoor Masjedi, Ramin Tajvidi, Seyed Mohammad Nasirodin Tabatabaei, Abdullah Khudhur Ahmed, Pierre Singer, Ilya Kagan, Merav Rigler, Daniel Belman, Phillip Levin, Belal Harara, Adei Diab, Fayez Abilama, Rebecca Ibrahim, Aya Fares, Ahmad Buimsaedah, Marwa Gamra, Ahmed Aqeelah, Almajdoub Ali Mohammed Ali, Ahmed Gaber Sadik Homaidan, Bushray Almiqlash, Hala Bilkhayr, Ahmad Bouhuwaish, Ahmed Sa Taher, Eman Abdulwahed, Fathi A
Cassini A, Plachouras D, Eckmanns T, Abu Sin M, Blank H-P, Ducomble T et al (2016) Burden of six healthcare-associated infections on European population health: estimating incidence-based disability-adjusted life years through a population prevalence-based modelling study. PLoS Med 13(10):e1002150 DOI: 10.1371/journal.pmed.1002150
Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F et al (2012) Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 38(12):1930–1945 DOI: 10.1007/s00134-012-2695-9
Vincent JL, Sakr Y, Singer M, Martin-Loeches I, Machado FR, Marshall JC et al (2020) Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 323(15):1478–1487 DOI: 10.1001/jama.2020.2717
Adrie C, Garrouste-Orgeas M, Ibn Essaied W, Schwebel C, Darmon M, Mourvillier B et al (2017) Attributable mortality of ICU-acquired bloodstream infections: impact of the source, causative micro-organism, resistance profile and antimicrobial therapy. J Infect 74(2):131–141 DOI: 10.1016/j.jinf.2016.11.001
Prowle JR, Echeverri JE, Ligabo EV, Sherry N, Taori GC, Crozier TM et al (2011) Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality. Crit Care 15(2):R100 DOI: 10.1186/cc10114
De Waele JJ, Akova M, Antonelli M, Canton R, Carlet J, De Backer D et al (2018) Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multi-drug resistance. Intensive Care Med 44(2):189–196
Bezabih YM, Bezabih A, Dion M, Batard E, Teka S, Obole A et al (2022) Comparison of the global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli between healthcare and community settings: a systematic review and meta-analysis. JAC Antimicrob Resist 76(1):22–29
World Health Organization (2021) Global antimicrobial resistance and use surveillance system (GLASS) report: 2021
Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A et al (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399(10325):629–655 DOI: 10.1016/S0140-6736(21)02724-0
Cosgrove SE (2006) The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 42(Suppl 2):S82-89 DOI: 10.1086/499406
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344–349 DOI: 10.1016/j.jclinepi.2007.11.008
Buetti N, Tabah A, Loiodice A, Ruckly S, Aslan AT, Montrucchio G et al (2022) Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study. Crit Care 26(1):319 DOI: 10.1186/s13054-022-04166-y
UN Statistics Division. Standard country and area codes for statistical use. https://unstats.un.org/unsd/methodology/m49/. Accessed 1 July 2022
Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270(24):2957–2963 DOI: 10.1001/jama.1993.03510240069035
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H et al (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22(7):707–710
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315(8):801–810 DOI: 10.1001/jama.2016.0287
Center for disease control and prevention C (2019) Carbapenem-resistant enterobacterales (CRE): CRE technical information. https://www.cdc.gov/hai/organisms/cre/technical-info.html#Definition. Accessed 1 July 2022
Kadri SS, Adjemian J, Lai YL, Spaulding AB, Ricotta E, Prevots DR et al (2018) Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis 67(12):1803–1814
Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94(446):496–509 DOI: 10.1080/01621459.1999.10474144
European Centre for Disease Prevention and Control (2019) Healthcare-associated infections acquired in intensive care units. In: ECDC. Annual epidemiological report for 2017. https://www.ecdc.europa.eu/en/publications-data/healthcare-associated-infections-intensive-care-units-annual-epidemiological-1. Accessed 1 July 2022
Bonnet V, Dupont H, Glorion S, Aupee M, Kipnis E, Gerard JL et al (2019) Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study). J Hosp Infect 102(3):317–324 DOI: 10.1016/j.jhin.2019.01.011
Huh K, Chung DR, Ha YE, Ko JH, Kim SH, Kim MJ et al (2020) Impact of difficult-to-treat resistance in gram-negative bacteremia on mortality: retrospective analysis of nationwide surveillance data. Clin Infect Dis 71(9):e487–e496
Giacobbe DR, Giani T, Bassetti M, Marchese A, Viscoli C, Rossolini GM (2020) Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications. Clin Microbiol Infect 26(6):713–722 DOI: 10.1016/j.cmi.2019.09.023
Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP et al (2015) Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis 61(7):1071–1080 DOI: 10.1093/cid/civ447
Weinberger J, Rhee C, Klompas M (2020) A critical analysis of the literature on time-to-antibiotics in suspected sepsis. J Infect Dis 222(Suppl 2):S110–S118 DOI: 10.1093/infdis/jiaa146
Hranjec T, Rosenberger LH, Swenson B, Metzger R, Flohr TR, Politano AD et al (2012) Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis 12(10):774–780 DOI: 10.1016/S1473-3099(12)70151-2
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C et al (2021) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 47(11):1181–1247 DOI: 10.1007/s00134-021-06506-y
Curran J, Lo J, Leung V, Brown K, Schwartz KL, Daneman N et al (2022) Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis. Clin Microbiol Infect 28(4):479–490 DOI: 10.1016/j.cmi.2021.10.022
Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH et al (2016) A clinical decision tree to predict whether a bacteremic patient is infected with an extended-spectrum beta-lactamase-producing organism. Clin Infect Dis 63(7):896–903 DOI: 10.1093/cid/ciw425
Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP et al (2007) Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 44(2):159–177 DOI: 10.1086/510393
Heffernan AJ, Mohd Sazlly Lim S, Lipman J, Roberts JA (2021) A personalised approach to antibiotic pharmacokinetics and pharmacodynamics in critically ill patients. Anaesth Crit Care Pain Med 40(6):100970 DOI: 10.1016/j.accpm.2021.100970
Tabah A, Lipman J, Barbier F, Buetti N, Timsit J-F (2022) Use of antimicrobials for bloodstream infections in the intensive care unit, a clinically oriented review. Antibiotics 11(3):362 DOI: 10.3390/antibiotics11030362
Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M et al (2021) Hospital-acquired infections in critically ill patients with COVID-19. Chest 160(2):454–465 DOI: 10.1016/j.chest.2021.04.002
Buetti N, Ruckly S, de Montmollin E, Reignier J, Terzi N, Cohen Y et al (2021) COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network. Intensive Care Med 47(2):180–187 DOI: 10.1007/s00134-021-06346-w