{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:24:35Z","timestamp":1774063475974,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Carbapenem-resistant <jats:italic>Enterobacterales<\/jats:italic> (CRE) are resistant to several other classes of antimicrobials, reducing treatment options and increasing mortality. We studied the clinical characteristics and burden of hospitalized adult patients with CRE infections in a setting where treatment options are limited.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A retrospective cohort study included adult inpatients between January 2015\u2013December 2019 at Siriraj Hospital in Bangkok, Thailand. Clinical and microbiological data were reviewed.<\/jats:p><jats:p>R<jats:bold>esults<\/jats:bold>: Of 420 patients with CRE infections, the mean age was 65.00 \u00b1 18.89\u00a0years, 192 (45.72%) were male, and 112 (26.90%) were critically ill. Three hundred and eighty (90.48%) had <jats:italic>Klebsiella pneumoniae<\/jats:italic>, and 40 (9.52%) had <jats:italic>Escherichia coli<\/jats:italic> infections. The mean APACHE II score was 14.27 \u00b1 6.36. Nearly half had previous hospitalizations (48.81%), 41.2% received antimicrobials, and 88.1% had undergone medical procedures before the onset of infection. The median time of onset of CRE infection was 16\u00a0days after admission. Common sites of infection were bacteremia (53.90%) and pneumonia (45.47%). Most CRE-infected patients had septic shock (63.10%) and Gram-negative co-infections (62.85%). Colistin (29.95%) and non-colistin (12.91%) monotherapies, and colistin-based (44.78%) and non-colistin-based (12.36%) combination therapies were the best available antimicrobial therapies (BAAT). The median length of hospitalization was 31\u00a0days, and the median hospitalization cost was US$10,435. The in-hospital mortality rate was 68.33%. Septic shock [adjusted odds ratio (aOR) 10.73, 5.65\u201320.42, <jats:italic>p<\/jats:italic> &amp;lt;0 .001], coinfection (aOR 2.43, 1.32\u20134.47, <jats:italic>p<\/jats:italic> = 0.004), mechanical ventilation (aOR 2.33, 1.24\u20134.36, <jats:italic>p<\/jats:italic> = 0.009), and a high SOFA score at onset (aOR 1.18, 1.07\u20131.30, <jats:italic>p<\/jats:italic> &amp;lt;0 .001) were associated with mortality.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> CRE infection increases mortality, hospital stays, and healthcare costs. A colistin-based regimen was the BAAT in this study. Therefore, newer antimicrobial agents are urgently needed.<\/jats:p>","DOI":"10.3389\/fphar.2022.972900","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T09:37:54Z","timestamp":1662111474000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The burden of carbapenem-resistant Enterobacterales infection in a large Thai tertiary care hospital"],"prefix":"10.3389","volume":"13","author":[{"given":"Watcharaphon","family":"Tangsawad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chayanis","family":"Kositamongkol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piriyaporn","family":"Chongtrakool","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pochamana","family":"Phisalprapa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anupop","family":"Jitmuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.4103\/ijmr.IJMR_2086_17","article-title":"Susceptibility profile, resistance mechanisms & efficacy ratios of fosfomycin, nitrofurantoin & colistin for carbapenem-resistant Enterobacteriaceae causing urinary tract infections","volume":"149","author":"Amladi","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"48.e9","DOI":"10.1016\/j.cmi.2016.09.003","article-title":"Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States","volume":"23","author":"Bartsch","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"B3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1086\/649020","article-title":"Attributable costs of enterococcal bloodstream infections in a nonsurgical hospital cohort","volume":"31","author":"Butler","year":"2010","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"B4","first-page":"S35","article-title":"Epidemiology of infections caused by multidrug-resistant gram-negative bacteria in adult hospitalized patients at Siriraj Hospital","volume":"97","author":"Chaisathaphol","year":"2014","journal-title":"J. Med. Assoc. Thai"},{"key":"B5","doi-asserted-by":"publisher","first-page":"461","DOI":"10.2147\/IDR.S192540","article-title":"Epidemiology of carbapenem-resistant enterobacteriaceae: A 5-year experience at a tertiary care hospital","volume":"12","author":"Chotiprasitsakul","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"B6","volume-title":"Performance Standards for antimicrobial susceptibility testing","year":"2017"},{"key":"B7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1186\/s12879-016-1979-z","article-title":"A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome","volume":"16","author":"de Maio Carrilho","year":"2016","journal-title":"BMC Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/j.cmi.2019.04.013","article-title":"Management of carbapenem-resistant Enterobacteriaceae infections","volume":"25","author":"Durante-Mangoni","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"B9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13054-020-2742-9","article-title":"Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae","volume":"24","author":"Falcone","year":"2020","journal-title":"Crit. Care"},{"key":"B10","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","article-title":"CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting","volume":"36","author":"Horan","year":"2008","journal-title":"Am. J. Infect. Control"},{"key":"B11","first-page":"198","article-title":"Implementation of the world health organization\u2019s global antimicrobial resistance surveillance system (GLASS) for the surveillance of sputum specimens collected from patients at Siriraj hospital","volume":"103","author":"Jitmuang","year":"2020","journal-title":"J. Med. Assoc. Thai"},{"key":"B12","doi-asserted-by":"publisher","first-page":"516","DOI":"10.3947\/ic.2020.52.4.516","article-title":"Fosfomycin dosing regimens based on Monte Carlo simulation for treated carbapenem-resistant enterobacteriaceae infection","volume":"52","author":"Kanchanasurakit","year":"2020","journal-title":"Infect. Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e140","DOI":"10.3346\/jkms.2019.34.e140","article-title":"Prevalence and risk factors of carbapenem-resistant enterobacteriaceae acquisition in an emergency intensive care unit in a tertiary hospital in korea: A case-control study","volume":"34","author":"Kang","year":"2019","journal-title":"J. Korean Med. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/ice.2021.446","article-title":"Clinical and economic outcomes attributable to carbapenem-resistant Enterobacterales and delayed appropriate antibiotic therapy in hospitalized patients","author":"Kengkla","year":"2021","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2935","DOI":"10.1590\/1518-8345.1751.2935","article-title":"Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae","volume":"25","author":"Lavagnoli","year":"2017","journal-title":"Rev. Lat. Am. Enferm."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1086\/656378","article-title":"Economic impact of Acinetobacter baumannii infection in the intensive care unit","volume":"31","author":"Lee","year":"2010","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"E615","DOI":"10.3390\/antibiotics9090615","article-title":"Evaluation of intravenous fosfomycin disodium dosing regimens in critically ill patients for treatment of carbapenem-resistant Enterobacterales infections using Monte Carlo simulation","volume":"9","author":"Leelawattanachai","year":"2020","journal-title":"Antibiot. (Basel)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S156","DOI":"10.1093\/infdis\/jiz574","article-title":"Risk factors and molecular epidemiology of complicated intra-abdominal infections with carbapenem-resistant enterobacteriaceae: A multicenter study in China","volume":"221","author":"Liu","year":"2020","journal-title":"J. Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13756-018-0346-9","article-title":"A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States","volume":"7","author":"Livorsi","year":"2018","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"B20","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.diagmicrobio.2005.02.007","article-title":"Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia","volume":"52","author":"Lodise","year":"2005","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0186195","DOI":"10.1371\/journal.pone.0186195","article-title":"Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study","volume":"12","author":"McConville","year":"2017","journal-title":"PLoS One"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/cid\/ciz530","article-title":"RESTORE-IMI 1: A multicenter, randomized, double-blind trial comparing efficacy and safety of imipenem\/relebactam vs colistin plus imipenem in patients with imipenem-nonsusceptible bacterial infections","volume":"70","author":"Motsch","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1017\/ice.2016.145","article-title":"Costs and mortality associated with multidrug-resistant healthcare-associated acinetobacter infections","volume":"37","author":"Nelson","year":"2016","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e3126","DOI":"10.1097\/MD.0000000000003126","article-title":"Tigecycline treatment for carbapenem-resistant enterobacteriaceae infections: A systematic review and meta-analysis","volume":"95","author":"Ni","year":"2016","journal-title":"Med. Baltim."},{"key":"B25","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s10096-018-3438-9","article-title":"Risk factors for carbapenem-resistant enterobacteriaceae infections: A French case-control-control study","volume":"38","author":"Nicolas-Chanoine","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3390\/antibiotics11030355","article-title":"Antimicrobial activity profiles and potential antimicrobial regimens against carbapenem-resistant Enterobacterales isolated from multi-centers in western Thailand","volume":"11","author":"Nulsopapon","year":"2022","journal-title":"Antibiot. (Basel)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.cmi.2020.03.035","article-title":"Colistin plus meropenem for carbapenem-resistant gram-negative infections: In vitro synergism is not associated with better clinical outcomes","volume":"26","author":"Nutman","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"B28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13756-021-00950-7","article-title":"Molecular epidemiology of carbapenem-resistant Enterobacterales in Thailand, 2016-2018","volume":"10","author":"Paveenkittiporn","year":"2021","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1080\/13696998.2020.1803889","article-title":"Cost-effectiveness and budget impact analysis of infliximab and its biosimilar in patients with refractory moderate-to-severe Crohn's disease using real world evidence in Thailand","volume":"23","author":"Phisalprapa","year":"2020","journal-title":"J. Med. Econ."},{"key":"B30","first-page":"1666","article-title":"Comparative colistin susceptibility testing methods for Escherichia coli and Klebsiella pneumoniae","volume":"101","author":"Ruangkriengsin","year":"2018","journal-title":"J. Med. Assoc. Thai"},{"key":"B31","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jgar.2019.11.009","article-title":"Implementation of global antimicrobial resistance surveillance system (GLASS) in patients with bacteriuria","volume":"20","author":"Sirijatuphat","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0190132","DOI":"10.1371\/journal.pone.0190132","article-title":"Implementation of global antimicrobial resistance surveillance system (GLASS) in patients with bacteremia","volume":"13","author":"Sirijatuphat","year":"2018","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1094","DOI":"10.1097\/ipc.0000000000001094","article-title":"Factors affecting clinical outcomes of carbapenem-resistant Enterobacteriaceae and carbapenem-susceptible Enterobacteriaceae infections","volume":"30","author":"Soontaros","year":"2022","journal-title":"Infect. Dis. Clin. Pract. Balt. Md."},{"key":"B34","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jgar.2021.05.006","article-title":"Antibiotic susceptibility profiles and prevalence of co-colistin and carbapenem-resistant Enterobacteriaceae isolated from patients in a university hospital in Southern Thailand","volume":"26","author":"Szekely","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B35","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/cid\/cix783","article-title":"Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant enterobacteriaceae","volume":"66","author":"van Duin","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1007\/s10096-016-2710-0","article-title":"Risk factors and clinical outcomes for carbapenem-resistant Enterobacteriaceae nosocomial infections","volume":"35","author":"Wang","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e01864-19","DOI":"10.1128\/JCM.01864-19","article-title":"The clinical and laboratory Standards institute subcommittee on antimicrobial susceptibility testing: Background, organization, functions, and processes","volume":"58","author":"Weinstein","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s40121-018-0214-1","article-title":"Effect and safety of meropenem-vaborbactam versus best-available therapy in patients with carbapenem-resistant enterobacteriaceae infections: The TANGO II randomized clinical trial","volume":"7","author":"Wunderink","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.ijantimicag.2017.03.011","article-title":"In vitro antibacterial activity of fosfomycin combined with other antimicrobials against KPC-producing Klebsiella pneumoniae","volume":"50","author":"Yu","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0067521","DOI":"10.1128\/AAC.00675-21","article-title":"Nationwide surveillance and molecular characterization of critically drug-resistant gram-negative bacteria: Results of the research university network Thailand study","volume":"65","author":"Yungyuen","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.2147\/IDR.S298530","article-title":"Risk factors for and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae nosocomial infections: A retrospective study in a tertiary hospital in beijing, China","volume":"14","author":"Zhang","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01882-17","article-title":"Epidemiology of carbapenem-resistant enterobacteriaceae infections: Report from the China CRE network","volume":"62","author":"Zhang","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.3389\/fmicb.2019.02957","article-title":"Colistin combined with tigecycline: A promising alternative strategy to combat Escherichia coli harboring bla (ndm-) (5) and mcr-1","volume":"10","author":"Zhou","year":"2019","journal-title":"Front. Microbiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.972900\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T09:38:04Z","timestamp":1662111484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.972900\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":43,"alternative-id":["10.3389\/fphar.2022.972900"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.972900","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"article-number":"972900"}}