{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:11:45Z","timestamp":1788372705084,"version":"build-2803163510"},"reference-count":202,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in developing and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management\u2019s most important yet controversial components and summarize the available evidence from the last two decades.<\/jats:p>","DOI":"10.3390\/microorganisms11092231","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"2231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Management of Sepsis and Septic Shock: What Have We Learned in the Last Two Decades?"],"prefix":"10.3390","volume":"11","author":[{"given":"Shiwani","family":"Kamath","sequence":"first","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, The University of Oklahoma Health Sciences Center, The Oklahoma City VA Health Care System, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1795-7517","authenticated-orcid":false,"given":"Hiba","family":"Hammad Altaq","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, The University of Oklahoma Health Sciences Center, The Oklahoma City VA Health Care System, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-7573","authenticated-orcid":false,"given":"Tony","family":"Abdo","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, The University of Oklahoma Health Sciences Center, The Oklahoma City VA Health Care System, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ccc.2008.12.003","article-title":"Sepsis and Septic Shock: A History","volume":"25","author":"Funk","year":"2009","journal-title":"Crit. Care Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5152\/TJAR.2017.93753","article-title":"Changing Definitions of Sepsis","volume":"45","author":"Gul","year":"2017","journal-title":"Turk. J. Anaesthesiol. Reanim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1097\/01.CCM.0000050454.01978.3B","article-title":"2001 SCCM\/ESICM\/ACCP\/ATS\/SIS International Sepsis Definitions Conference","volume":"31","author":"Levy","year":"2003","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations","volume":"193","author":"Fleischmann","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s13054-022-04176-w","article-title":"Trends in mortality in septic patients according to the different organ failure during 15 years","volume":"26","author":"Vela","year":"2022","journal-title":"Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1186\/s13054-020-02978-4","article-title":"Recommendations for fluid management of adults with sepsis in sub-Saharan Africa: A systematic review of guidelines","volume":"24","author":"Silberberg","year":"2020","journal-title":"Crit. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1001\/jama.2017.10913","article-title":"Effect of an Early Resuscitation Protocol on In-hospital Mortality among Adults with Sepsis and Hypotension: A Randomized Clinical Trial","volume":"318","author":"Andrews","year":"2017","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1378\/chest.112.1.235","article-title":"Sepsis: A New Hypothesis for Pathogenesis of the Disease Process","volume":"112","author":"Bone","year":"1997","journal-title":"Chest"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S1473-3099(07)70265-7","article-title":"Host\u2013pathogen interactions in sepsis","volume":"8","author":"Opal","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"628302","DOI":"10.3389\/fmed.2021.628302","article-title":"Sepsis\u2014Pathophysiology and Therapeutic Concepts","volume":"8","author":"Jarczak","year":"2021","journal-title":"Front. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJM200103083441001","article-title":"Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis","volume":"344","author":"Bernard","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1056\/NEJMoa1202290","article-title":"Drotrecogin Alfa (Activated) in Adults with Septic Shock","volume":"366","author":"Ranieri","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1001\/jama.2016.20328","article-title":"Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality among Adults with Suspected Infection Admitted to the Intensive Care Unit","volume":"317","author":"Raith","year":"2017","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1001\/jama.2016.20329","article-title":"Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality among Patients with Suspected Infection Presenting to the Emergency Department","volume":"317","author":"Freund","year":"2017","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.chest.2017.12.015","article-title":"A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality: A Systematic Review and Meta-Analysis","volume":"153","author":"Serafim","year":"2018","journal-title":"Chest"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13054-018-1952-x","article-title":"Performance of the quick Sequential (sepsis-related) Organ Failure Assessment score as a prognostic tool in infected patients outside the intensive care unit: A systematic review and meta-analysis","volume":"22","author":"Song","year":"2018","journal-title":"Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e205191","DOI":"10.1001\/jamanetworkopen.2020.5191","article-title":"Comparison of Early Warning Scoring Systems for Hospitalized Patients with and Without Infection at Risk for In-Hospital Mortality and Transfer to the Intensive Care Unit","volume":"3","author":"Liu","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1164\/rccm.201604-0854OC","article-title":"Quick Sepsis-related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit","volume":"195","author":"Churpek","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e0043","DOI":"10.1097\/CCE.0000000000000043","article-title":"Accuracy of Quick Sequential Organ Failure Assessment Score to Predict Sepsis Mortality in 121 Studies Including 1,716,017 Individuals: A Systematic Review and Meta-Analysis","volume":"1","author":"Herwanto","year":"2019","journal-title":"Crit. Care Explor."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Damiani, E., Donati, A., Serafini, G., Rinaldi, L., Adrario, E., Pelaia, P., Busani, S., and Girardis, M. (2015). Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125827"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1056\/NEJM199510193331601","article-title":"A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients. SvO2 Collaborative Group","volume":"333","author":"Gattinoni","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1056\/NEJMoa010307","article-title":"Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock","volume":"345","author":"Rivers","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1097\/01.CCM.0000117317.18092.E4","article-title":"Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock","volume":"32","author":"Dellinger","year":"2004","journal-title":"Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1056\/NEJMoa1401602","article-title":"A randomized trial of protocol-based care for early septic shock","volume":"370","author":"Yealy","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1056\/NEJMoa1404380","article-title":"Goal-directed resuscitation for patients with early septic shock","volume":"371","author":"Investigators","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJMoa1500896","article-title":"Trial of Early, Goal-Directed Resuscitation for Septic Shock","volume":"372","author":"Mouncey","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1056\/NEJMoa1701380","article-title":"Early, Goal-Directed Therapy for Septic Shock-A Patient-Level Meta-Analysis","volume":"376","author":"Investigators","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/CCM.0000000000002255","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016","volume":"45","author":"Rhodes","year":"2017","journal-title":"Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/01.CCM.0000298158.12101.41","article-title":"Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008","volume":"36","author":"Dellinger","year":"2008","journal-title":"Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1097\/CCM.0b013e31827e83af","article-title":"Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012","volume":"41","author":"Dellinger","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1097\/CCM.0000000000003892","article-title":"Antibiotic- and Fluid-Focused Bundles Potentially Improve Sepsis Management, but High-Quality Evidence Is Lacking for the Specificity Required in the Centers for Medicare and Medicaid Service\u2019s Sepsis Bundle (SEP-1)*","volume":"47","author":"Pepper","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"558","DOI":"10.7326\/M17-2947","article-title":"Evidence Underpinning the Centers for Medicare & Medicaid Services\u2019 Severe Sepsis and Septic Shock Management Bundle (SEP-1): A Systematic Review","volume":"168","author":"Pepper","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMoa1703058","article-title":"Time to Treatment and Mortality during Mandated Emergency Care for Sepsis","volume":"376","author":"Seymour","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00134-018-5085-0","article-title":"The Surviving Sepsis Campaign Bundle: 2018 update","volume":"44","author":"Levy","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.annemergmed.2018.06.046","article-title":"The 2018 Surviving Sepsis Campaign\u2019s Treatment Bundle: When Guidelines Outpace the Evidence Supporting Their Use","volume":"73","author":"Spiegel","year":"2019","journal-title":"Ann. Emerg. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1001\/jama.2019.9021","article-title":"Association Between State-Mandated Protocolized Sepsis Care and In-hospital Mortality among Adults with Sepsis","volume":"322","author":"Kahn","year":"2019","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2138596","DOI":"10.1001\/jamanetworkopen.2021.38596","article-title":"Association between Implementation of the Severe Sepsis and Septic Shock Early Management Bundle Performance Measure and Outcomes in Patients with Suspected Sepsis in US Hospitals","volume":"4","author":"Rhee","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.chest.2021.07.2167","article-title":"Effects of Compliance with the Early Management Bundle (SEP-1) on Mortality Changes among Medicare Beneficiaries with Sepsis: A Propensity Score Matched Cohort Study","volume":"161","author":"Townsend","year":"2022","journal-title":"Chest"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.kint.2019.05.026","article-title":"Acute kidney injury from sepsis: Current concepts, epidemiology, pathophysiology, prevention and treatment","volume":"96","author":"Peerapornratana","year":"2019","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0140-6736(00)04211-2","article-title":"Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: A multicentre randomised study","volume":"357","author":"Schortgen","year":"2001","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"f839","DOI":"10.1136\/bmj.f839","article-title":"Hydroxyethyl starch 130\/0.38\u20130.45 versus crystalloid or albumin in patients with sepsis: Systematic review with meta-analysis and trial sequential analysis","volume":"346","author":"Haase","year":"2013","journal-title":"BMJ"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1056\/NEJMoa1204242","article-title":"Hydroxyethyl Starch 130\/0.42 versus Ringer\u2019s Acetate in Severe Sepsis","volume":"367","author":"Perner","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1056\/NEJMoa1209759","article-title":"Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care","volume":"367","author":"Myburgh","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"347","DOI":"10.7326\/M14-0178","article-title":"Fluid Resuscitation in Sepsis: A systematic review and network meta-analysis","volume":"161","author":"Rochwerg","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1001\/jama.2013.280502","article-title":"Effects of Fluid Resuscitation with Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting with Hypovolemic Shock: The CRISTAL randomized trial","volume":"310","author":"Annane","year":"2013","journal-title":"JAMA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1056\/NEJMoa040232","article-title":"A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit","volume":"350","author":"Finfer","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1097\/01.CCM.0000239119.57544.0C","article-title":"Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study*","volume":"34","author":"Dubois","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJMoa1305727","article-title":"Albumin Replacement in Patients with Severe Sepsis or Septic Shock","volume":"370","author":"Caironi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1186\/s13063-020-04921-y","article-title":"Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): Protocol for a randomized controlled trial","volume":"21","author":"Sakr","year":"2020","journal-title":"Trials"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1097\/SLA.0b013e31825074f5","article-title":"Major Complications, Mortality, and Resource Utilization After Open Abdominal Surgery","volume":"255","author":"Shaw","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1001\/jama.2012.13356","article-title":"Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults","volume":"308","author":"Yunos","year":"2012","journal-title":"JAMA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJMoa2114464","article-title":"Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults","volume":"386","author":"Finfer","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/00003246-200202000-00006","article-title":"Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: Improved short-term survival and acid-base balance with Hextend compared with saline","volume":"30","author":"Kellum","year":"2002","journal-title":"Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1378\/chest.125.1.243","article-title":"Effects of Hyperchloremic Acidosis on Arterial Pressure and Circulating Inflammatory Molecules in Experimental Sepsis","volume":"125","author":"Kellum","year":"2004","journal-title":"Chest"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/SLA.0b013e318256be72","article-title":"A Randomized, Controlled, Double-Blind Crossover Study on the Effects of 2-L Infusions of 0.9% Saline and Plasma-Lyte\u00ae 148 on Renal Blood Flow Velocity and Renal Cortical Tissue Perfusion in Healthy Volunteers","volume":"256","author":"Chowdhury","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1001\/jama.2015.12334","article-title":"Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial","volume":"314","author":"Young","year":"2015","journal-title":"JAMA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1164\/rccm.201607-1345OC","article-title":"Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial","volume":"195","author":"Semler","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1711586","article-title":"Balanced Crystalloids versus Saline in Noncritically Ill Adults","volume":"378","author":"Self","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1711584","article-title":"Balanced Crystalloids versus Saline in Critically Ill Adults","volume":"378","author":"Semler","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1164\/rccm.201903-0557OC","article-title":"Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial","volume":"200","author":"Brown","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/1060028019866420","article-title":"Balanced Crystalloids versus Saline in Critically Ill Adults: A Systematic Review and Meta-Analysis","volume":"54","author":"Hammond","year":"2020","journal-title":"Ann. Pharmacother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1001\/jama.2021.11684","article-title":"Effect of Intravenous Fluid Treatment with a Balanced Solution vs. 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial","volume":"326","author":"Zampieri","year":"2021","journal-title":"JAMA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"EVIDoa2100010","DOI":"10.1056\/EVIDoa2100010","article-title":"Balanced Crystalloids versus Saline in Critically Ill Adults\u2014A Systematic Review with Meta-Analysis","volume":"1","author":"Hammond","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_69","first-page":"1248","article-title":"Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): A cluster, crossover, randomized, controlled trial","volume":"47","author":"Ramanan","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e0613","DOI":"10.1097\/CCE.0000000000000613","article-title":"Saline Compared to Balanced Crystalloid in Patients with Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"4","author":"Alghamdi","year":"2022","journal-title":"Crit. Care Explor."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1007\/s00134-015-4134-1","article-title":"Passive leg raising for predicting fluid responsiveness: A systematic review and meta-analysis","volume":"42","author":"Monnet","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s00134-015-4168-4","article-title":"Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness","volume":"42","author":"Eskesen","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00134-016-4573-3","article-title":"Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: A systematic review and meta-analysis","volume":"43","author":"Silversides","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1097\/CCM.0000000000000541","article-title":"Simplified Severe Sepsis Protocol: A randomized controlled trial of modified early goal-directed therapy in Zambia","volume":"42","author":"Andrews","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R10","DOI":"10.1186\/cc9410","article-title":"Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: A self-reported, continent-wide survey of anaesthesia providers","volume":"15","author":"Baelani","year":"2011","journal-title":"Crit. Care"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"103255","DOI":"10.1016\/j.iccn.2022.103255","article-title":"Sepsis protocols to reduce mortality in resource-restricted settings: A systematic review","volume":"72","author":"Taj","year":"2022","journal-title":"Intensive Crit. Care Nurs."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.chest.2019.11.050","article-title":"Lower vs Higher Fluid Volumes During Initial Management of Sepsis: A Systematic Review with Meta-Analysis and Trial Sequential Analysis","volume":"157","author":"Meyhoff","year":"2020","journal-title":"Chest"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1056\/NEJMoa2202707","article-title":"Restriction of Intravenous Fluid in ICU Patients with Septic Shock","volume":"386","author":"Meyhoff","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, Shapiro, N.I., Douglas, I.S., Brower, R.G., Brown, S.M., Exline, M.C., Ginde, A.A., Gong, M.N., Grissom, C.K., and Hayden, D. (2023). Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N. Engl. J. Med., 388, 499\u2013510.","DOI":"10.1056\/NEJMoa2212663"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1056\/NEJMoa0907118","article-title":"Comparison of Dopamine and Norepinephrine in the Treatment of Shock","volume":"362","author":"Biston","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Avni, T., Lador, A., Lev, S., Leibovici, L., Paul, M., and Grossman, A. (2015). Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129305"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJMra002709","article-title":"The Pathogenesis of Vasodilatory Shock","volume":"345","author":"Landry","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1007\/s00134-004-2283-8","article-title":"Role of vasopressin in the management of septic shock","volume":"30","author":"Mutlu","year":"2004","journal-title":"Intensive Care Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/00000542-200203000-00011","article-title":"Beneficial Effects of Short-term Vasopressin Infusion during Severe Septic Shock","volume":"96","author":"Patel","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1007\/s001340101014","article-title":"The effects of vasopressin on hemodynamics and renal function in severe septic shock: A case series","volume":"27","author":"Holmes","year":"2001","journal-title":"Intensive Care Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1056\/NEJMoa067373","article-title":"Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock","volume":"358","author":"Russell","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00134-011-2407-x","article-title":"Vasopressin for treatment of vasodilatory shock: An ESICM systematic review and meta-analysis","volume":"38","author":"Polito","year":"2012","journal-title":"Intensive Care Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"R154","DOI":"10.1186\/cc11469","article-title":"Vasopressin and terlipressin in adult vasodilatory shock: A systematic review and meta-analysis of nine randomized controlled trials","volume":"16","author":"Neto","year":"2012","journal-title":"Crit. Care"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Belletti, A., Musu, M., Silvetti, S., Saleh, O., Pasin, L., Monaco, F., Hajjar, L.A., Fominskiy, E., Finco, G., and Zangrillo, A. (2015). Non-Adrenergic Vasopressors in Patients with or at Risk for Vasodilatory Shock. A Systematic Review and Meta-Analysis of Randomized Trials. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142605"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00134-009-1687-x","article-title":"The effects of vasopressin on acute kidney injury in septic shock","volume":"36","author":"Gordon","year":"2010","journal-title":"Intensive Care Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1001\/jama.2016.10485","article-title":"Effect of Early Vasopressin vs. Norepinephrine on Kidney Failure in Patients with Septic Shock: The VANISH Randomized Clinical Trial","volume":"316","author":"Gordon","year":"2016","journal-title":"JAMA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1001\/jama.2018.4528","article-title":"Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone with Atrial Fibrillation in Patients with Distributive Shock: A Systematic Review and Meta-analysis","volume":"319","author":"McIntyre","year":"2018","journal-title":"JAMA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1007\/s00134-019-05620-2","article-title":"Vasopressin in septic shock: An individual patient data meta-analysis of randomised controlled trials","volume":"45","author":"Nagendran","year":"2019","journal-title":"Intensive Care Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13613-022-01021-9","article-title":"Timing of vasoactive agents and corticosteroid initiation in septic shock","volume":"12","author":"Ammar","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13054-022-03911-7","article-title":"Vasopressor Choice and Timing in Vasodilatory Shock","volume":"26","author":"Wieruszewski","year":"2022","journal-title":"Crit. Care"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1007\/s00134-008-1219-0","article-title":"A comparison of epinephrine and norepinephrine in critically ill patients","volume":"34","author":"Myburgh","year":"2008","journal-title":"Intensive Care Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0140-6736(07)61344-0","article-title":"Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial","volume":"370","author":"Annane","year":"2007","journal-title":"Lancet"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1097\/01.CCM.0000063045.77339.B6","article-title":"Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best?*","volume":"31","author":"Creteur","year":"2003","journal-title":"Crit. Care Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1186\/cc7121","article-title":"Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: A randomized, controlled trial","volume":"12","author":"Morelli","year":"2008","journal-title":"Crit. Care"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2017.2841","article-title":"Association Between US Norepinephrine Shortage and Mortality among Patients with Septic Shock","volume":"317","author":"Vail","year":"2017","journal-title":"JAMA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.chest.2022.04.147","article-title":"Comparison of Heart Rate After Phenylephrine vs Norepinephrine Initiation in Patients with Septic Shock and Atrial Fibrillation","volume":"162","author":"Law","year":"2022","journal-title":"Chest"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/s13054-014-0534-9","article-title":"Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): A pilot study","volume":"18","author":"Chawla","year":"2014","journal-title":"Crit. Care"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1056\/NEJMoa1704154","article-title":"Angiotensin II for the Treatment of Vasodilatory Shock","volume":"377","author":"Khanna","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s13054-023-04446-1","article-title":"Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: An exploratory post-hoc analysis of the ATHOS-3 clinical trial","volume":"27","author":"Wieruszewski","year":"2023","journal-title":"Crit. Care"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1097\/CCM.0000000000003092","article-title":"Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II","volume":"46","author":"Tumlin","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/0885066620972943","article-title":"A Multicenter Observational Cohort Study of Angiotensin II in Shock","volume":"37","author":"Smith","year":"2022","journal-title":"J. Intensive Care Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.chest.2020.08.2074","article-title":"Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use","volume":"159","author":"Wieruszewski","year":"2021","journal-title":"Chest"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13054-017-1798-7","article-title":"Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients","volume":"21","author":"Russell","year":"2017","journal-title":"Crit. Care"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1001\/jama.2019.14607","article-title":"Effect of Selepressin vs. Placebo on Ventilator- and Vasopressor-Free Days in Patients with Septic Shock: The SEPSIS-ACT Randomized Clinical Trial","volume":"322","author":"Laterre","year":"2019","journal-title":"JAMA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"653.e9","DOI":"10.1016\/j.jcrc.2015.01.014","article-title":"A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters","volume":"30","author":"Loubani","year":"2015","journal-title":"J. Crit. Care"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/1742-6723.13406","article-title":"Safety of peripheral administration of vasopressor medications: A systematic review","volume":"32","author":"Tian","year":"2020","journal-title":"Emerg. Med. Australas"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/jhm.2394","article-title":"Safety of peripheral intravenous administration of vasoactive medication","volume":"10","author":"Schaub","year":"2015","journal-title":"J. Hosp. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1097\/CCM.0b013e31828a42c5","article-title":"Central or Peripheral Catheters for Initial Venous Access of ICU Patients: A randomized controlled trial","volume":"41","author":"Ricard","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/20477724.2022.2038051","article-title":"Norepinephrine may improve survival of septic shock patients in a low-resource setting: A proof-of-concept study on feasibility and efficacy outside the Intensive Care Unit","volume":"116","author":"Bima","year":"2022","journal-title":"Pathog Glob Health"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S2213-2600(17)30469-1","article-title":"Prehospital antibiotics in the ambulance for sepsis: A multicentre, open label, randomised trial","volume":"6","author":"Alam","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/S1473-3099(12)70151-2","article-title":"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","volume":"12","author":"Hranjec","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1097\/01.CCM.0000217961.75225.E9","article-title":"Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*","volume":"34","author":"Kumar","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1164\/rccm.201609-1848OC","article-title":"The Timing of Early Antibiotics and Hospital Mortality in Sepsis","volume":"196","author":"Liu","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1007\/s00134-016-4415-3","article-title":"Sepsis in resource-limited settings\u2013expert consensus recommendations group of the European Society of Intensive Care Medicine (ESICM); The Mahidol-Oxford Research Unit (MORU) in Bangkok, Thailand Recommendations for infection management in patients with sepsis and septic shock in resource-limited settings","volume":"42","author":"Thwaites","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13054-021-03883-0","article-title":"Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: A prospective nationwide multicenter cohort study","volume":"26","author":"Im","year":"2022","journal-title":"Crit. Care"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.chest.2021.06.029","article-title":"Antibiotic Timing and Progression to Septic Shock among Patients in the ED with Suspected Infection","volume":"161","author":"Bisarya","year":"2022","journal-title":"Chest"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1378\/chest.09-0087","article-title":"Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock","volume":"136","author":"Kumar","year":"2009","journal-title":"Chest"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1093\/jac\/dkq373","article-title":"Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia","volume":"65","author":"Paul","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1086\/375057","article-title":"Outcomes Analysis of Delayed Antibiotic Treatment for Hospital-Acquired Staphylococcus aureus Bacteremia","volume":"36","author":"Lodise","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1900057","DOI":"10.1183\/13993003.00057-2019","article-title":"Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: A cohort study","volume":"54","author":"Webb","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1001\/jamainternmed.2019.7495","article-title":"Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia","volume":"180","author":"Jones","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e02432-16","DOI":"10.1128\/AAC.02432-16","article-title":"Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia","volume":"61","author":"Baby","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.chest.2018.10.014","article-title":"Outcomes Associated with De-escalating Therapy for Methicillin-Resistant Staphylococcus aureus in Culture-Negative Nosocomial Pneumonia","volume":"155","author":"Cowley","year":"2019","journal-title":"Chest"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jinf.2016.11.013","article-title":"Empirical mono-versus combination antibiotic therapy in adult intensive care patients with severe sepsis\u2013A systematic review with meta-analysis and trial sequential analysis","volume":"74","author":"Perner","year":"2017","journal-title":"J. Infect."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/cid\/cis305","article-title":"Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control","volume":"54","author":"Kollef","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/cc7964","article-title":"Determinants of mortality in non-neutropenic ICU patients with Candidaemia","volume":"13","author":"Marriott","year":"2009","journal-title":"Crit. Care"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00134-014-3310-z","article-title":"A multicenter study of septic shock due to candidemia: Outcomes and predictors of mortality","volume":"40","author":"Bassetti","year":"2014","journal-title":"Intensive Care Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1001\/jama.2016.14655","article-title":"Empirical Micafungin Treatment and Survival without Invasive Fungal Infection in Adults with ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial","volume":"316","author":"Timsit","year":"2016","journal-title":"JAMA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1200\/JCO.2017.77.6211","article-title":"Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update","volume":"36","author":"Taplitz","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00134-019-05866-w","article-title":"Antimicrobial de-escalation in critically ill patients: A position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP)","volume":"46","author":"Tabah","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2018.12179","article-title":"Antibiotics for Sepsis\u2014Finding the Equilibrium","volume":"320","author":"Klompas","year":"2018","journal-title":"JAMA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/cid\/ciy1054","article-title":"Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial","volume":"69","author":"Yahav","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1056\/NEJMoa1411162","article-title":"Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection","volume":"372","author":"Sawyer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1001\/jama.290.19.2588","article-title":"Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: A randomized trial","volume":"290","author":"Chastre","year":"2003","journal-title":"JAMA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"ofy026","DOI":"10.1093\/ofid\/ofy026","article-title":"Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality for Multidrug-Resistant Organism Infections","volume":"5","author":"Burnham","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"ofz408","DOI":"10.1093\/ofid\/ofz408","article-title":"Early Infectious Disease Consultation Is Associated with Lower Mortality in Patients with Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle","volume":"6","author":"Madaline","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ccc.2017.08.010","article-title":"Biomarkers in Sepsis","volume":"34","author":"Wiersinga","year":"2018","journal-title":"Crit. Care Clin."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s00134-018-5141-9","article-title":"Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: A randomized multicenter study","volume":"44","author":"Daubin","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the american thoracic society and infectious diseases society of America","volume":"200","author":"Metlay","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2200735","DOI":"10.1183\/13993003.00735-2022","article-title":"ERS\/ESICM\/ESCMID\/ALAT guidelines for the management of severe community-acquired pneumonia","volume":"61","author":"Torres","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1097\/CCM.0b013e31821e8791","article-title":"Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: A randomized trial*","volume":"39","author":"Jensen","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jamainternmed.2016.2514","article-title":"Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients with Severe Sepsis or Septic Shock: A Randomized Clinical Trial","volume":"176","author":"Bloos","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S1473-3099(16)00053-0","article-title":"Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: A randomised, controlled, open-label trial","volume":"16","author":"Beishuizen","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1164\/rccm.200708-1238OC","article-title":"Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients: A randomized trial","volume":"177","author":"Nobre","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"dlad057","DOI":"10.1093\/jacamr\/dlad057","article-title":"C-reactive protein and procalcitonin use in adults in low- and middle-income countries: A narrative review","volume":"5","author":"Lamrous","year":"2023","journal-title":"JAC-Antimicrobial. Resist."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.chest.2022.12.049","article-title":"Monocyte Distribution Width as a Diagnostic Marker for Infection: A Systematic Review and Meta-analysis","volume":"164","author":"Malinovska","year":"2023","journal-title":"Chest"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1097\/CCM.0000000000005820","article-title":"Comparison of the Diagnostic Accuracies of Monocyte Distribution Width, Procalcitonin, and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis","volume":"51","author":"Huang","year":"2023","journal-title":"Crit. Care Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"36","DOI":"10.7326\/0003-4819-81-1-36","article-title":"Clinical Trial Design in Studies of Corticosteroids for Bacterial Infections","volume":"81","author":"Weitzman","year":"1974","journal-title":"Ann. Intern. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1172\/JCI102441","article-title":"Effect of cortisone on acute streptococcal infections and post-streptococcal complications 1","volume":"30","author":"Hahn","year":"1951","journal-title":"J. Clin. Investig."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJM198709103171101","article-title":"A Controlled Clinical Trial of High-Dose Methylprednisolone in the Treatment of Severe Sepsis and Septic Shock","volume":"317","author":"Bone","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"The Veterans Administration Systemic Sepsis Cooperative Study Group (1987). Effect of High-Dose Glucocorticoid Therapy on Mortality in Patients with Clinical Signs of Systemic Sepsis. N. Engl. J. Med., 317, 659\u2013665.","DOI":"10.1056\/NEJM198709103171102"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/infdis\/165.1.1","article-title":"Guidelines for the use of systemic glucocorticosteroids in the management of selected infections. Working Group on Steroid Use, Antimicrobial Agents Committee, Infectious Diseases Society of America","volume":"165","author":"McGowan","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1097\/00003246-199507000-00021","article-title":"Steroid controversy in sepsis and septic shock: A meta-analysis","volume":"23","author":"Lefering","year":"1995","journal-title":"Crit. Care Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1097\/00003246-199508000-00019","article-title":"Corticosteroid treatment for sepsis: A critical appraisal and meta-analysis of the literature","volume":"23","author":"Cronin","year":"1995","journal-title":"Crit. Care Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1001\/jama.283.8.1038","article-title":"A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin","volume":"283","author":"Annane","year":"2000","journal-title":"JAMA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1023\/A:1009870524359","article-title":"An Historical Review of Glucocorticoid Treatment in Sepsis. Disease Pathophysiology and the Design of Treatment Investigation","volume":"3","author":"Meduri","year":"1999","journal-title":"Sepsis"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1097\/00003246-199804000-00010","article-title":"Reversal of late septic shock with supraphysiologic doses of hydrocortisone","volume":"26","author":"Bollaert","year":"1998","journal-title":"Crit. Care Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1001\/jama.288.7.862","article-title":"Effect of Treatment with Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients with Septic Shock","volume":"288","author":"Annane","year":"2002","journal-title":"JAMA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa071366","article-title":"Hydrocortisone Therapy for Patients with Septic Shock","volume":"358","author":"Sprung","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_166","first-page":"CD002243","article-title":"Corticosteroids for treating sepsis","volume":"2015","author":"Annane","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1007\/s00134-015-3899-6","article-title":"Glucocorticosteroids for sepsis: Systematic review with meta-analysis and trial sequential analysis","volume":"41","author":"Volbeda","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1086\/599343","article-title":"Safety and Efficacy of Corticosteroids for the Treatment of Septic Shock: A Systematic Review and Meta-Analysis","volume":"49","author":"Sligl","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1001\/jama.2009.815","article-title":"Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults: A systematic review","volume":"301","author":"Annane","year":"2009","journal-title":"JAMA"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1001\/jama.2016.14799","article-title":"Effect of Hydrocortisone on Development of Shock among Patients with Severe Sepsis: The HYPRESS Randomized Clinical Trial","volume":"316","author":"Keh","year":"2016","journal-title":"JAMA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1705835","article-title":"Adjunctive Glucocorticoid Therapy in Patients with Septic Shock","volume":"378","author":"Venkatesh","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1705716","article-title":"Hydrocortisone plus Fludrocortisone for Adults with Septic Shock","volume":"378","author":"Annane","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1001\/jama.2010.2","article-title":"Corticosteroid treatment and intensive insulin therapy for septic shock in adults: A randomized controlled trial","volume":"303","author":"Investigators","year":"2010","journal-title":"JAMA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1001\/jamainternmed.2018.5849","article-title":"Association of Corticosteroid Treatment with Outcomes in Adult Patients with Sepsis: A Systematic Review and Meta-analysis","volume":"179","author":"Fang","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_175","first-page":"CD002243","article-title":"Corticosteroids for treating sepsis in children and adults","volume":"2019","author":"Annane","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00134-018-5197-6","article-title":"Low-dose corticosteroids for adult patients with septic shock: A systematic review with meta-analysis and trial sequential analysis","volume":"44","author":"Butler","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1001\/jamainternmed.2023.0258","article-title":"Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs. Hydrocortisone Alone among Patients with Septic Shock","volume":"183","author":"Bosch","year":"2023","journal-title":"JAMA Intern. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"EVIDoa2300034","DOI":"10.1056\/EVIDoa2300034","article-title":"Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock","volume":"2","author":"Pirracchio","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1056\/NEJM199902113400601","article-title":"A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group","volume":"340","author":"Hebert","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1056\/NEJMoa1406617","article-title":"Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock","volume":"371","author":"Holst","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1097\/CCM.0000000000002283","article-title":"Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial*","volume":"45","author":"Bergamin","year":"2017","journal-title":"Crit. Care Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s13054-019-2543-1","article-title":"Liberal versus restrictive red blood cell transfusion strategy in sepsis or septic shock: A systematic review and meta-analysis of randomized trials","volume":"23","author":"Hirano","year":"2019","journal-title":"Crit. Care"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1186\/cc3952","article-title":"The Surviving Sepsis Campaign sepsis change bundles and clinical practice","volume":"9","author":"Dellinger","year":"2005","journal-title":"Crit. Care"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1056\/NEJMoa011300","article-title":"Intensive Insulin Therapy in Critically Ill Patients","volume":"345","author":"Wouters","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa052521","article-title":"Intensive Insulin Therapy in the Medical ICU","volume":"354","author":"Wilmer","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"NICE-SUGAR Study Investigators, Finfer, S., Chittock, D.R., Su, S.Y., Blair, D., Foster, D., Dhingra, V., Bellomo, R., Cook, D., and Dodek, P. (2009). Intensive versus Conventional Glucose Control in Critically Ill Patients. N. Engl. J. Med., 360, 1283\u20131297.","DOI":"10.1056\/NEJMoa0810625"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00134-016-4523-0","article-title":"Glycemic control, mortality, and hypoglycemia in critically ill patients: A systematic review and network meta-analysis of randomized controlled trials","volume":"43","author":"Yamada","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2018). Diabetes Care in the Hospital: Standards of Medical Care in Diabetes\u20142018. Diabetes Care, 41, S144\u2013S151.","DOI":"10.2337\/dc18-S014"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.chest.2016.11.036","article-title":"Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study","volume":"151","author":"Marik","year":"2017","journal-title":"Chest"},{"key":"ref_190","first-page":"2","article-title":"Pro and Con: Vitamin C and Sepsis\u2013Con","volume":"29","author":"Ittoop","year":"2018","journal-title":"Soc. Crit. Care Anesthesiol. Newsl."},{"key":"ref_191","unstructured":"Harris, R. (2023, June 15). Doctor Turns Up Possible Treatment for Deadly Sepsis. Available online: https:\/\/www.npr.org\/sections\/health-shots\/2017\/03\/23\/521096488\/doctor-turns-up-possible-treatment-for-deadly-sepsis."},{"key":"ref_192","first-page":"1","article-title":"Pro and Con: Vitamin C and Sepsis\u2013Pro","volume":"29","author":"Zimick","year":"2018","journal-title":"Soc. Crit. Care Anesthesiol. Newsl."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/jama.2019.11825","article-title":"Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial","volume":"322","author":"Fowler","year":"2019","journal-title":"JAMA"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1001\/jama.2019.22176","article-title":"Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support among Patients with Septic Shock: The VITAMINS Randomized Clinical Trial","volume":"323","author":"Fujii","year":"2020","journal-title":"JAMA"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1001\/jama.2020.11946","article-title":"Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial","volume":"324","author":"Moskowitz","year":"2020","journal-title":"JAMA"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa2200644","article-title":"Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit","volume":"386","author":"Lamontagne","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1001\/jama.2020.24505","article-title":"Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients with Sepsis: The VICTAS Randomized Clinical Trial","volume":"325","author":"Sevransky","year":"2021","journal-title":"JAMA"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"107476","DOI":"10.1016\/j.pharmthera.2020.107476","article-title":"Immunotherapy in sepsis-brake or accelerate?","volume":"208","author":"Steinhagen","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1056\/NEJMra1208623","article-title":"Severe Sepsis and Septic Shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1001\/jama.2019.5791","article-title":"Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis","volume":"321","author":"Seymour","year":"2019","journal-title":"JAMA"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41746-022-00650-5","article-title":"Effectiveness of automated alerting system compared to usual care for the management of sepsis","volume":"5","author":"Zhang","year":"2022","journal-title":"NPJ Digit. Med."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/s41591-022-01894-0","article-title":"Prospective, multi-site study of patient outcomes after implementation of the TREWS machine learning-based early warning system for sepsis","volume":"28","author":"Adams","year":"2022","journal-title":"Nat. Med."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/9\/2231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:46:03Z","timestamp":1760129163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/9\/2231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,4]]},"references-count":202,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["microorganisms11092231"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11092231","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,4]]}}}