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Review

Pharmacological management of sepsis in adults with a focus on the current gold standard treatments and promising adjunctive strategies: evidence from the last five years

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Pages 991-1007 | Received 31 May 2018, Accepted 27 Feb 2019, Published online: 17 Mar 2019

References

  • Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–810.
  • Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–1596.
  • Rhodes A, Evans L, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–377.
  • Raith EP, Udy AA, Bailey M, et al. 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. JAMA. 2017;317:290–300.
  • Donnelly JP, Safford MM, Shapiro NI, et al. Application of the third international consensus definitions for sepsis (Sepsis-3) classification: a retrospective population-based cohort study. Lancet Infect Dis. 2017;17:661–670.
  • Park HK, Kim WY, Kim MC, et al. Quick sequential organ failure assessment compared to systemic inflammatory response syndrome for predicting sepsis in emergency department. J Crit Care. 2017;42:12–17.
  • Askim A, Moser F, Gustad LT, et al. Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality – a prospective study of patients admitted with infection to the emergency department. Scand J Trauma Resusc Emerg Med. 2017;25:56.
  • Tusgul S, Carron PN, Yersin B, et al. Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of complication in the prehospital setting and at the emergency department triage. Scand J Trauma Resusc Emerg Med. 2017;25:108.
  • Haydar S, Spanier M, Weems P, et al. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis. Am J Emerg Med. 2017;35:1730–1733.
  • Finkelsztein EJ, Jones DS, Ma KC, et al. Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit. Crit Care. 2017;21:73.
  • April MD, Aguirre J, Tannenbaum LI, et al. Sepsis clinical criteria in emergency department patients admitted to an intensive care unit: an external validation study of quick sequential organ failure assessment. J Emerg Med. 2017;52:622–631.
  • Churpek MM, Snyder A, Han X, et al. 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. Am J Respir Crit Care Med. 2017;195:906–911.
  • Boulos D, Shehabi Y, Moghaddas JA, et al. Predictive value of quick sepsis-related organ failure scores following sepsis-related medical emergency team calls: a retrospective cohort study. Anaesth Intensive Care. 2017;45:688–694.
  • Rudd KE, Seymour CW, Aluisio AR, et al. Association of the quick sequential (sepsis-related) organ failure assessment (qSOFA) score with excess hospital mortality in adults with suspected infection in low- and middle-income countries. JAMA. 2018;319:2202–2211.
  • Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:762–774.
  • Williams JM, Greenslade JH, McKenzie JV, et al. Systemic inflammatory response syndrome, quick sequential organ function assessment, and organ dysfunction: insights from a prospective database of ED patients with infection. Chest. 2017;151:586–596.
  • Solligård E, Damås JK. SOFA criteria predict infection-related in-hospital mortality in ICU patients better than SIRS criteria and the qSOFA score. Evid Based Med. 2017;22:211.
  • Giamarellos-Bourboulis EJ, Tsaganos T, Tsangaris I, et al. Validation of the new sepsis-3 definitions: proposal for improvement in early risk identification. Clin Microbiol Infect. 2017;23:104–109.
  • Freund Y, Lemachatti N, Krastinova E, et al. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA. 2017;317:301–308.
  • González Del Castillo J, Julian-Jiménez A, González-Martínez F, et al. Prognostic accuracy of SIRS criteria, qSOFA score and GYM score for 30-day-mortality in older non-severely dependent infected patients attended in the emergency department. Eur J Clin Microbiol Infect Dis. 2017;36:2361–2369.
  • Maitra S, Som A, Bhattacharjee S. Accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies. Clin Microbiol Infect. 2018. DOI:10.1016/j.cmi.2018.03.032.
  • Serafim R, Gomes JA, Salluh J, et al. A comparison of the quick-SOFA and systemic inflammatory response syndrome criteria for the diagnosis of sepsis and prediction of mortality. Chest. 2018;153:646–655.
  • Murri R, Taccari F, Palazzolo C, et al. IDSA did not endorse the surviving sepsis campaign guidelines. Clin Infect Dis. 2018;66:1815–1816.
  • The PRISM Investigators. Early, goal-directed therapy for septic shock - a patient-level meta-analysis. N Engl J Med. 2017;376:2223–2234.
  • Pruinelli L, Westra BL, Yadav P, et al. Delay within the 3-hour surviving sepsis campaign guideline on mortality for patients with severe sepsis and septic shock. Crit Care Med. 2018;46:500–505.
  • Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235–2244.
  • Bednarczyk JM, Fridfinnson JA, Kumar A, et al. Incorporating dynamic assessment of fluid responsiveness into goal-directed therapy: a systematic review and meta-analysis. Crit Care Med. 2017;45:1538–1545.
  • Peker N, Couto N, Sinha B, et al. Diagnosis of bloodstream infections from positive blood cultures and directly from blood samples: recent developments in molecular approaches. Clin Microbiol Infect. 2018;24:944–955.
  • Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42:1749–1755.
  • Koupetori M, Retsas T, Antonakos N, et al. Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome. BMC Infect Dis. 2014;14:272.
  • Palacios-Baena ZR, Gutiérrez-Gutiérrez B, Calbo E, et al. Empiric therapy with carbapenem-sparing regimens for bloodstream infections due to extended-spectrum β-lactamase-producing enterobacteriaceae: results from the INCREMENT cohort. Clin Infect Dis. 2017;65:1615–1623.
  • Justo JA, Bookstaver PB, Kohn J, et al. Combination therapy vs monotherapy for Gram-negative bloodstream infection: matching by predicted prognosis. Int J Antimicrob Agents. 2018;51:488–492.
  • Dulhunty JM, Roberts JA, Davis JS, et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis. 2013;56:236–244.
  • Carrié C, Petit L, d’Houdain N, et al. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study. Int J Antimicrob Agents. 2018;51:443–449.
  • Borsuk-de-Moor A, Rypulak E, Potrḙć B, et al. Population pharmacokinetics of high-dose tigecycline in patients with sepsis or septic shock. Antimicrob Agents Chemother. 2018;62:e02273–17.
  • Mohamed AF, Karaiskos I, Plachouras D, et al. Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill. Antimicrob Agents Chemother. 2012;56:4241–4249.
  • Kontopidou F, Giamarellou H, Katerelos P, et al. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care units in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014;20:O117–23.
  • Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018;18:391–400.
  • Nation RL, Garonzik SM, Thamlikitkul V, et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017;64:565–571.
  • Shields RK, Nguyen MH, Chen L, et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother. 2017;61:e00883–17.
  • Torres A, Zhong N, Pachl J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–295.
  • Kaye KS, Bhowmick T, Metallidis S, et al. Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA. 2018;319:788–799.
  • Boucher HW, Wilcox M, Talbot GH, et al. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370:2169–2179.
  • Wirz Y, Meier MA, Bouadma L, et al. Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials. Crit Care. 2018;22:191.
  • Gordon AC, Mason AJ, Perkins GD, et al. The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial. Crit Care Med. 2014;42:1325–1333.
  • Gordon AC, Perkins GD, Singer M, et al. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375:1638–1648.
  • Meng JB, Hu MH, Lai ZZ, et al. Levosimendan versus dobutamine in myocardial injury patients with septic shock: a randomized controlled trial. Med Sci Monit. 2016;22:148696.
  • Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419–430.
  • Avni T, Lador A, Lev S, et al. Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One. 2015;10:e0129305.
  • Annane D, Pastores SM, Rochweg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part I): society of critical care medicine (SCCM) and European society of intensive care medicine (ESICM). Crit Care Med. 2017;45:2078–2088.
  • Póvoa P, Salluh JI, Martinez ML, et al. Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial. Crit Care. 2015;19:193.
  • Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797–808.
  • Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378:809–818.
  • Tongyoo S, Permpikul C, Mongkolpun W, et al. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Crit Care. 2016;20:329.
  • Katsenos CS, Antonopoulou AN, Apostolidou EN, et al. Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response. Crit Care Med. 2014;42:1651–1657.
  • Giamarellos-Bourboulis EJ, Apostolidou E, Lada M, et al. Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome. Crit Care. 2013;17:R247.
  • Cavazzuti I, Serafini G, Busani S, et al. Early therapy with Igm-enriched polyclonal immunoglobulin in patients with septic shock. Intensive Care Med. 2014;40:1888–1896.
  • Giamarellos-Bourboulis EJ, Tziolos N, Routsi C, et al. Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins. Clin Microbiol Infect. 2016;22:499–506.
  • Tagami T, Matsui H, Fushimi K, et al. Intravenous immunoglobulin and mortality in pneumonia patients with septic shock: an observational nationwide stydy. Clin Infect Dis. 2015;61:385–392.
  • Tagami T, Matsui H, Fushimi K, et al. Intravenous immunoglobulin use in septic shock patients after emergency laparotomy. J Infect. 2015;71:158–166.
  • Ishikura H, Nakamura Y, Kawano Y, et al. Intravenous immunoglobulin improves sepsis-induced coagulopathy: A retrospective, single-center observational study. J Crit Care. 2015;30:579–583.
  • Toth I, Mikor A, Leiner T, et al. Effects of IgM-enriched immunoglobulin therapy in septic-shock-induced multiple organ failure: pilot study. J Anesth. 2013;27:618–622.
  • Welte T, Dellinger RP, Ebelt H, et al. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018;44:438–448.
  • Vincent JL, Marshall JC, Dellinger RP, et al. Talactoferrin in severe sepsis results from the phase II/III oral talactoferrin in severe sepsis trial. Crit Care Med. 2015;43:1832–1838.
  • Bernard GR, François B, Mira JP, et al. Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor necrosis factor-α fragment antibody AZD9773 in adult patients with severe sepsis and/or septic shock: randomized, double-blind, placebo-controlled phase IIb study. Crit Care Med. 2014;42:504–511.
  • Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of the macrophage activation syndrome: re-analysis of a prior phase III trial. Crit Care Med. 2016;44:275–281.
  • Uchida M, Abe T, Ono K, et al. Ulinastatin did not reduce mortality in elderly multiple organ failure patients: a retrospective observational study in a single center ICU. Acute Med Surg. 2017;5:90–97.
  • Karnad DR, Bhadade R, Verma PK, et al. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis a multicenter randomized controlled study. Intensive Care Med. 2014;40:830–838.
  • Sehgal IS, Agarwal R, Aggarwal AN, et al. A randomized trial of mycobacterium w in severe sepsis. J Crit Care. 2015;30:85–89.
  • Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock. a retrospective before-after study. Chest. 2017;151:1229–1238.
  • Woth G, Nagy B, Merei A, et al. The effect of Na-selenite treatment on the oxidative stress-antioxidants balance of multiple organ failure. J Crit Care. 2014;29:883.e7-11.
  • Donnino MW, Mortensen SJ, Andersen LW, et al. Ubiquinol (reduced coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial. Crit Care. 2015;19:275.
  • Janz DR, Bastarache JA, Rice TW, et al. randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the ACROSS trial. Crit Care Med. 2015;43:534–541.
  • Pickkers P, Mehta RL, Murray PT, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. JAMA. 2018;320:1998–2009
  • Beed M, Brindley PG, Mahajan R, et al. The association between prior statin use and long-term outcomes after critical care admission. J Crit Care. 2016;35:63–68.
  • Lee CC, Lee MG, Hsu TC, et al. A population-based cohort study on the drug-specific effect of statins on sepsis outcome. Chest. 2018;153:805–815.
  • Tagami T, Matsui H, Horiguchi H, et al. Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost. 2014;12:1470–1479.
  • Yasuda N, Goto K, Ohchi Y, et al. The efficacy and safety of antithrombin and recombinant human thrombomodulin combination therapy in patients with severe sepsis and disseminated intravascular coagulation. J Crit Care. 2016;36:29–34.
  • Preliminary results of overseas phase III clinical study for ART-123. [cited 2019 Feb 4]. Available at: https://www.asahi-kasei.co.jp/asahi/en/news/2018/e180802.html
  • Wu Q, Ren J, Wu X, et al. Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: a prospective study. J Crit Care. 2014;29:362–366.
  • Al Harbi SA, Tamim HM, Al-Dorzi HM, et al. Association between aspirin therapy and the outcome in critically ill patients: a nested cohort study. BMC Pharmacol Toxicol. 2016;17:5.
  • Wiewel MA, de Stoppelaar SF, van Vught LA, et al. Chronic antiplatelet therapy is not associated with alterations in the presentation, outcome, or host response biomarkers during sepsis: a propensity-matched analysis. Intensive Care Med. 2016;42:352–360.
  • Tsaganos T, Raftogiannis M, Pratikaki M, et al. Clarithromycin leads to long-term survival and cost benefit in ventilator-associated pneumonia and sepsis. Antimicrob Agents Chemother. 2016;60:3640–3646.
  • Giamarellos-Bourboulis EJ, Mylona V, Antonopoulou A, et al. Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial. J Antimicrob Chemother. 2014;69:1111–1118.
  • Kyriazopoulou K, Leventogiannis K, Norrby-Teglund A, et al. Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis. BMC Med. 2017;15:172.
  • Meyer NJ, Reilly JP, Anderson BJ, et al. Mortality benefit of recombinant human interleukin-1 receptor antagonist for sepsis varies by initial interleukin-1 receptor antagonist plasma concentration. Crit Care Med. 2018;46:21–28.
  • Kumar S, Gupta E, Kaushik S, et al. Evaluation of oxidative stress and antioxidant status: correlation with the severity of sepsis. Scand J Immunol. 2018;87:e12653.
  • Fowler AA, Syed AA, Knowlson S, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32.
  • Christodoulou S, Kyriazopoulou K, Chrysanthakopoulou M, et al. Lipid peroxidation in Gram-negative bacteremia modulates the risk for septic shock and infections by resistant Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis. 2017;36:2171–2177.
  • Choudhury S, Kannan K, Addison MP, et al. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis. Vascul Pharmacol. 2015;71:139–150.
  • Wiewel MA, Scicluna BP, van Vught LA, et al. The host response in critically ill sepsis patients on statin therapy: a prospective observational study. Ann Intensive Care. 2018;8:9.
  • Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–874.
  • Leentjens J, Kox M, Koch RM, et al. Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study. Am J Respir Crit Care Med. 2012;186:838–845.
  • Venet B, Demart J, Blaise BJ, et al. IL-7 restores T lymphocyte immunometabolic failure in septic shock patients through mTOR activation. J Immunol. 2017;199:1606–1615.
  • Francois B, Jeannet R, Daix T, et al. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018;3:e98960.
  • Nie W, Li B, Xiu Q. β-lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis. J Antimicrob Chemother. 2014;69:1441–1446.
  • Horita N, Otsuka T, Haranaga S, et al. Beta-lactam plus macrolides or beta-lactam alone for community-acquired pneumonia: A systematic review and meta-analysis. Respirology. 2016;21:1193–1200.
  • Garin N, Genné D, Carballo S, et al. β-lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. JAMA Intern Med. 2014;174:1894–1901.
  • McIntyre LA, Stewart DJ, Mei SHJ, et al. Cellular immunotherapy for septic shock. a phase I clinical trial. Am J Respir Crit Care Med. 2018;197:337–347.
  • He X, Ai S, Guo W, et al. Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: a phase 1 clinical trial. Transl Res. 2018;199:52–61.

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