{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T07:22:42Z","timestamp":1794208962037,"version":"4.8.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p\u2009=\u20090.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35\u20130.84], p\u2009=\u20090.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15\u20131.17], p\u2009=\u20090.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86\u20131.02], p\u2009=\u20090.047).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-023-08329-2","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T05:03:02Z","timestamp":1684818182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study"],"prefix":"10.1186","volume":"23","author":[{"given":"Shanshan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"8329_CR1","doi-asserted-by":"publisher","first-page":"e0166527","DOI":"10.1371\/journal.pone.0166527","volume":"11","author":"M Holmbom","year":"2016","unstructured":"Holmbom M, Giske CG, Fredrikson M, et al. 14-Year survey in a swedish county reveals a pronounced increase in bloodstream infections (BSI). Comorbidity - an independent risk factor for both BSI and mortality. PLoS ONE. 2016;11:e0166527.","journal-title":"PLoS ONE"},{"key":"8329_CR2","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3201\/eid2710.204826","volume":"27","author":"KSK Kontula","year":"2021","unstructured":"Kontula KSK, Skogberg K, Ollgren J, et al. Population-based study of bloodstream infection incidence and mortality rates, Finland, 2004\u20132018. Emerg Infect Dis. 2021;27:256\u20139.","journal-title":"Emerg Infect Dis"},{"key":"8329_CR3","doi-asserted-by":"publisher","first-page":"e0242921","DOI":"10.1128\/jcm.02429-21","volume":"60","author":"M Verway","year":"2022","unstructured":"Verway M, Brown KA, Marchand-Austin A, et al. Prevalence and Mortality Associated with Bloodstream Organisms: a Population-Wide retrospective cohort study. J Clin Microbiol. 2022;60:e0242921.","journal-title":"J Clin Microbiol"},{"key":"8329_CR4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13054-015-0795-y","volume":"19","author":"K Marquet","year":"2015","unstructured":"Marquet K, Liesenborgs A, Bergs J, et al. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Crit Care. 2015;19:63.","journal-title":"Crit Care"},{"key":"8329_CR5","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1056\/NEJMoa1703058","volume":"376","author":"CW Seymour","year":"2017","unstructured":"Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235\u201344.","journal-title":"N Engl J Med"},{"key":"8329_CR6","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/CCM.0000000000002235","volume":"45","author":"AC Kalil","year":"2017","unstructured":"Kalil AC, Johnson DW, Lisco SJ, et al. Early goal-directed therapy for sepsis: a novel solution for discordant survival outcomes in clinical trials. Crit Care Med. 2017;45:607\u201314.","journal-title":"Crit Care Med"},{"key":"8329_CR7","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","volume":"47","author":"L Evans","year":"2021","unstructured":"Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181\u2013247.","journal-title":"Intensive Care Med"},{"key":"8329_CR8","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/jac\/dkt477","volume":"69","author":"C Slimings","year":"2014","unstructured":"Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother. 2014;69:881\u201391.","journal-title":"J Antimicrob Chemother"},{"key":"8329_CR9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2334-14-13","volume":"14","author":"BG Bell","year":"2014","unstructured":"Bell BG, Schellevis F, Stobberingh E, et al. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014;14:13.","journal-title":"BMC Infect Dis"},{"key":"8329_CR10","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/j.ajic.2017.04.005","volume":"45","author":"R Hiensch","year":"2017","unstructured":"Hiensch R, Poeran J, Saunders-Hao P, et al. Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates. Am J Infect Control. 2017;45:1091\u2013100.","journal-title":"Am J Infect Control"},{"key":"8329_CR11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1513\/AnnalsATS.201806-419OC","volume":"16","author":"R Cangemi","year":"2019","unstructured":"Cangemi R, Falcone M, Taliani G, et al. Corticosteroid use and incident myocardial infarction in adults hospitalized for community-acquired pneumonia. Ann Am Thorac Soc. 2019;16:91\u20138.","journal-title":"Ann Am Thorac Soc"},{"key":"8329_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13054-020-2742-9","volume":"24","author":"M Falcone","year":"2020","unstructured":"Falcone M, Bassetti M, Tiseo G, et al. Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae. Crit Care (London Engl). 2020;24:29.","journal-title":"Crit Care (London Engl)"},{"key":"8329_CR13","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1093\/cid\/ciw110","volume":"62","author":"EJ Zasowski","year":"2016","unstructured":"Zasowski EJ, Claeys KC, Lagnf AM, et al. Time is of the essence: the impact of delayed antibiotic therapy on patient outcomes in hospital-onset Enterococcal bloodstream infections. Clin Infect Dis. 2016;62:1242\u201350.","journal-title":"Clin Infect Dis"},{"key":"8329_CR14","doi-asserted-by":"publisher","first-page":"3510","DOI":"10.1128\/AAC.00338-07","volume":"51","author":"TP Lodise Jr","year":"2007","unstructured":"Lodise TP Jr, Patel N, Kwa A, et al. Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother. 2007;51:3510\u20135.","journal-title":"Antimicrob Agents Chemother"},{"key":"8329_CR15","doi-asserted-by":"publisher","first-page":"dlac121","DOI":"10.1093\/jacamr\/dlac121","volume":"4","author":"A Oliva","year":"2022","unstructured":"Oliva A, Volpicelli L, Di Bari S, et al. Effect of ceftazidime\/avibactam plus fosfomycin combination on 30-day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study. JAC Antimicrob Resist. 2022;4:dlac121.","journal-title":"JAC Antimicrob Resist"},{"key":"8329_CR16","doi-asserted-by":"publisher","first-page":"791","DOI":"10.7326\/0003-4819-137-10-200211190-00007","volume":"137","author":"ND Friedman","year":"2002","unstructured":"Friedman ND, Kaye KS, Stout JE, et al. Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med. 2002;137:791\u20137.","journal-title":"Ann Intern Med"},{"key":"8329_CR17","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for Sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801\u201310.","journal-title":"JAMA"},{"key":"8329_CR18","unstructured":"CDC\/NHSN Surveillance Definitions for Specific Types of Infections. https:\/\/www.cdc.gov\/nhsn\/PDFs\/pscManual\/17pscNosInfDef_current.pdf."},{"key":"8329_CR19","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"AP Magiorakos","year":"2012","unstructured":"Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268\u201381.","journal-title":"Clin Microbiol Infect"},{"key":"8329_CR20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1473-3099(20)30477-1","volume":"21","author":"SS Kadri","year":"2021","unstructured":"Kadri SS, Lai YL, Warner S, et al; forming the National Insititutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI), et al. Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals. Lancet Infect Dis. 2021;21:241\u201351.","journal-title":"Lancet Infect Dis"},{"key":"8329_CR21","doi-asserted-by":"publisher","first-page":"e2249353","DOI":"10.1001\/jamanetworkopen.2022.49353","volume":"6","author":"T Ohnuma","year":"2023","unstructured":"Ohnuma T, Chihara S, Costin B, et al. Association of appropriate empirical antimicrobial therapy with In-Hospital mortality in patients with bloodstream infections in the US. JAMA Netw Open. 2023;6:e2249353.","journal-title":"JAMA Netw Open"},{"key":"8329_CR22","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1093\/cid\/cis588","volume":"55","author":"M Tumbarello","year":"2012","unstructured":"Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by KPC-producing Klebsiella pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943\u201350.","journal-title":"Clin Infect Dis"},{"key":"8329_CR23","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1128\/AAC.06268-11","volume":"56","author":"ZA Qureshi","year":"2012","unstructured":"Qureshi ZA, Paterson DL, Potoski BA, et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56:2108\u201313.","journal-title":"Antimicrob Agents Chemother"},{"key":"8329_CR24","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.1128\/AAC.02166-13","volume":"58","author":"GL Daikos","year":"2014","unstructured":"Daikos GL, Tsaousi S, Tzouvelekis LS, et al. Carbapenemaseproducing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58:2322\u201328.","journal-title":"Antimicrob Agents Chemother"},{"key":"8329_CR25","doi-asserted-by":"crossref","unstructured":"Falcone M, Russo A, Iacovelli A et al. Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Microbiol Infect 2016.","DOI":"10.1016\/j.cmi.2016.01.016"},{"key":"8329_CR26","unstructured":": 444\u201350."},{"key":"8329_CR27","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.ijantimicag.2013.09.002","volume":"42","author":"Y Hu","year":"2013","unstructured":"Hu Y, Li L, Li W, et al. Combination antibiotic therapy versus monotherapy for Pseudomonas aeruginosa bacteraemia: a meta-analysis of retrospective and prospective studies. Int J Antimicrob Agents. 2013;42:492\u20136.","journal-title":"Int J Antimicrob Agents"},{"key":"8329_CR28","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1128\/AAC.03007-15","volume":"60","author":"A Gomez-Simmonds","year":"2016","unstructured":"Gomez-Simmonds A, Nelson B, Eiras DP, et al. Combination regimens for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother. 2016;60:3601\u201307.","journal-title":"Antimicrob Agents Chemother"},{"key":"8329_CR29","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1136\/bmj.38028.520995.63","volume":"328","author":"M Paul","year":"2004","unstructured":"Paul M, Benuri-Silbiger I, Soares-Weiser K, et al. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and metaanalysis of randomised trials. BMJ. 2004;328:668.","journal-title":"BMJ"},{"key":"8329_CR30","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1473-3099(04)01108-9","volume":"4","author":"N Safdar","year":"2004","unstructured":"Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A metaanalysis. Lancet Infect Dis. 2004;4:519\u201327.","journal-title":"Lancet Infect Dis"},{"key":"8329_CR31","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1097\/CCM.0b013e3181e96b91","volume":"38","author":"A Kumar","year":"2010","unstructured":"Kumar A, Safdar N, Kethireddy S, et al. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic\/meta-regression study. Crit Care Med. 2010;38:1651\u201364.","journal-title":"Crit Care Med"},{"key":"8329_CR32","unstructured":"Guti\u00e9rrez-Guti\u00e9rrez B, Salamanca E, de Cueto M et al. For the REIPI\/ESGBIS\/INCREMENT investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis 2017; published online April 22."},{"key":"8329_CR33","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1097\/CCM.0000000000002255","volume":"45","author":"A Rhodes","year":"2017","unstructured":"Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45:486\u2013552.","journal-title":"Crit Care Med"},{"key":"8329_CR34","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1128\/AAC.00627-10","volume":"54","author":"M Paul","year":"2010","unstructured":"Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54:4851\u201363.","journal-title":"Antimicrob Agents Chemother"},{"key":"8329_CR35","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.cmi.2018.07.026","volume":"25","author":"P Puerta-Alcalde","year":"2018","unstructured":"Puerta-Alcalde P, Cardozo C, Su\u00e1rez-Lled\u00f3 M, et al. Current time-to-positivity of blood cultures in the febrile neutropenia: a tool to be used in stewardship de-escalation strategies. Clin Microbiol Infect. 2018;25:447\u201353.","journal-title":"Clin Microbiol Infect"},{"key":"8329_CR36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jbiotec.2016.12.022","volume":"243","author":"RH Deurenberg","year":"2017","unstructured":"Deurenberg RH, Bathoorn E, Chlebowicz MA, et al. Application of next generation sequencing in clinical microbiology and infection prevention. J Biotechnol. 2017;243:16\u201324.","journal-title":"J Biotechnol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-023-08329-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-023-08329-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-023-08329-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T05:03:06Z","timestamp":1684818186000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-023-08329-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["8329"],"URL":"https:\/\/doi.org\/10.1186\/s12879-023-08329-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2800701\/v1","asserted-by":"object"}]},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]},"assertion":[{"value":"11 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The protocols used in this retrospective study were reviewed and approved by the institutional ethics board of Beijing Tongren Hospital. The requirement for individual informed consent was waived by the institutional ethics board of Beijing Tongren Hospital because this study used currently existing medical records collected during the course of routine medical care and did not pose any additional risks to the patients. All patient data were anonymized prior to the analysis. All methods and experimental protocols in this study were conducted in accordance with the approved protocols and Ethics Committee\u2019s existing guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"344"}}