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Clinical Management of Endotoxemia: Antibiotics

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Endotoxin Induced-Shock: a Multidisciplinary Approach in Critical Care

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Abstract

Adequate antimicrobial therapy is pivotal in the management of patients with sepsis and is associated with improved clinical outcomes. However, this intervention may be associated with potential harms as well as challenged by concurrent patient and pathogen characteristics that may limit its efficacy. For these reasons, antimicrobic choice should be driven by evidence-based stewardship programs that take into account the severity of organ dysfunction, pharmacokinetic/pharmacodynamic characteristics of the drug, and the emergence of multi-drug resistant pathogens. Furthermore, it requires constant monitoring and careful re-evaluation to attempt de-escalation. Moreover, the emergence of multi-drug resistance pathogens has raised attention towards new molecules with marked antimicrobial properties as well as old drug molecules with narrow therapeutic windows (e.g., polymyxins).

Accordingly, clinicians should be aware of newly developed diagnostic tools and therapeutic drugs that may help maximize the adequacy of antimicrobial prescription and monitoring, in order to best improve the outcomes of patients with sepsis.

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References

  1. Marshall J, Foster D, Vincent J, Cook D, Cohen J, Dellinger R, et al. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis. 2004;190(3):527–34.

    Article  CAS  Google Scholar 

  2. Vincent J, Sakr Y, Singer M, Martin-Loeches I, Machado F, Marshall J, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020;323(15):1478–87.

    Article  Google Scholar 

  3. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith C, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–247.

    Article  Google Scholar 

  4. Ferrer R, Artigas A, Suarez D, Palencia E, Levy M, Arenzana A, et al. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med. 2009;180(9):861–6.

    Article  CAS  Google Scholar 

  5. Kalil A, Johnson D, Lisco S, Sun J. Early goal-directed therapy for sepsis: a novel solution for discordant survival outcomes in clinical trials. Crit Care Med. 2017;45(4):607–14.

    Article  Google Scholar 

  6. Seymour C, Gesten F, Prescott H, Friedrich M, Iwashyna T, Phillips G, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235–44.

    Article  Google Scholar 

  7. Kumar A, Roberts D, Wood K, Light B, Parrillo J, Sharma S, 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(6):1589–96.

    Article  Google Scholar 

  8. Liu V, Fielding-Singh V, Greene J, Baker J, Iwashyna T, Bhattacharya J, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196(7):856–63.

    Article  Google Scholar 

  9. Wunderink R, Srinivasan A, Barie P, Chastre J, Cruz CD, Douglas I, et al. Antibiotic stewardship in the intensive care unit. An Official American Thoracic Society workshop report in collaboration with the AACN, CHEST, CDC, and SCCM. Ann Am Thorac Soc. 2020;17(5):531–40.

    Article  Google Scholar 

  10. Kollef M, Bassetti M, Francois B, Burnham J, Dimopoulos G, Garnacho-Montero J, et al. The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship. Intensive Care Med. 2017;43(9):1187–97.

    Article  Google Scholar 

  11. De Waele J, Schouten J, Beovic B, Tabah A, Leone M. Antimicrobial de-escalation as part of antimicrobial stewardship in intensive care: no simple answers to simple questions-a viewpoint of experts. Intensive Care Med. 2020;46(2):236–44.

    Article  Google Scholar 

  12. Posteraro B, Cortazzo V, Liotti F, Menchinelli G, Ippoliti C, De Angelis G, et al. Diagnosis and treatment of bacterial pneumonia in critically ill patients with COVID-19 using a multiplex PCR assay: a large Italian hospital’s five-month experience. Microbiol Spectr. 2021;9(3):e0069521.

    Article  Google Scholar 

  13. Tängdén T, Martín VR, Felton T, Nielsen E, Marchand S, Brüggemann R, et al. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Med. 2017;43(7):1021–32.

    Article  Google Scholar 

  14. Udy A, Roberts J, Lipman J. Clinical implications of antibiotic pharmacokinetic principles in the critically ill. Intensive Care Med. 2013;39(12):2070–82.

    Article  CAS  Google Scholar 

  15. Roberts J, Abdul-Aziz M, Lipman J, Mouton J, Vinks A, Felton T, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.

    Article  Google Scholar 

  16. Udy A, Roberts J, Boots R, Paterson D, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1–16.

    Article  CAS  Google Scholar 

  17. Jamal J, Economou C, Lipman J, Roberts J. Improving antibiotic dosing in special situations in the ICU: burns, renal replacement therapy and extracorporeal membrane oxygenation. Curr Opin Crit Care. 2012;18(5):460–71.

    Article  Google Scholar 

  18. Roberts J, Taccone F, Lipman J. Understanding PK/PD. Intensive Care Med. 2016;42(11):1797–800.

    Article  Google Scholar 

  19. Abdul-Aziz M, Alffenaar J, Bassetti M, Bracht H, Dimopoulos G, Marriott D, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper. Intensive Care Med. 2020;46(6):1127–53.

    Article  Google Scholar 

  20. Roberts J, Roger C, Waele JD. Personalized antibiotic dosing for the critically ill. Intensive Care Med. 2019;45(5):715–8.

    Article  Google Scholar 

  21. Roberts J, Paul S, Akova M, Bassetti M, Waele JD, Dimopoulos G, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072–83.

    Article  CAS  Google Scholar 

  22. Pea F, Viale P, Cojutti P, Furlanut M. Dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients with severe gram-negative infections: a pharmacokinetics/pharmacodynamics-based approach. Antimicrob Agents Chemother. 2012;56(12):6343–8.

    Article  CAS  Google Scholar 

  23. Adembri C, Cappellini I, Novelli A. The role of PK/PD-based strategies to preserve new molecules against multi-drug resistant gram-negative strains. J Chemother. 2020;32(5):219–25.

    Article  Google Scholar 

  24. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The “old” and the “new” antibiotics for MDR Gram-negative pathogens: for whom, when, and how. Front Public Health. 2019;7:151.

    Article  Google Scholar 

  25. Moyá B, Zamorano L, Juan C, Ge Y, Oliver A. Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010;54(9):3933–7.

    Article  Google Scholar 

  26. Cho J, Fiorenza M, Estrada S. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination. Pharmacotherapy. 2015;35(7):701–15.

    Article  CAS  Google Scholar 

  27. Kollef M, Nováček M, Kivistik Ü, Réa-Neto Á, Shime N, Martin-Loeches I, et al. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019;19(12):1299–311.

    Article  CAS  Google Scholar 

  28. Karaiskos I, Galani I, Souli M, Giamarellou H. Novel β-lactam-β-lactamase inhibitor combinations: expectations for the treatment of carbapenem-resistant Gram-negative pathogens. Expert Opin Drug Metab Toxicol. 2019;15(2):133–49.

    Article  CAS  Google Scholar 

  29. Burgos R, Biagi M, Rodvold K, Danziger L. Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection. Expert Opin Drug Metab Toxicol. 2018;14(10):1007–21.

    Article  CAS  Google Scholar 

  30. Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(9):e00567–17.

    Article  CAS  Google Scholar 

  31. Li H, Estabrook M, Jacoby G, Nichols W, Testa R, Bush K. In vitro susceptibility of characterized β-lactamase-producing strains tested with avibactam combinations. Antimicrob Agents Chemother. 2015;59(3):1789–93.

    Article  CAS  Google Scholar 

  32. Ito A, Kohira N, Bouchillon S, West J, Rittenhouse S, Sader H, et al. In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria. J Antimicrob Chemother. 2016;71(3):670–7.

    Article  CAS  Google Scholar 

  33. Lasko M, Nicolau D. Carbapenem-resistant enterobacterales: considerations for treatment in the era of new antimicrobials and evolving enzymology. Curr Infect Dis Rep. 2020;22(3):6.

    Article  Google Scholar 

  34. Storm D, Rosenthal K, Swanson P. Polymyxin and related peptide antibiotics. Annu Rev Biochem. 1977;46:723–63.

    Article  CAS  Google Scholar 

  35. Evans M, Feola D, Rapp R. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999;33(9):960–7.

    Article  CAS  Google Scholar 

  36. Shoji H, Tani T, Hanasawa K, Kodama M. Extracorporeal endotoxin removal by polymyxin B immobilized fiber cartridge: designing and antiendotoxin efficacy in the clinical application. Ther Apher. 1998;2(1):3–12.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency, Anaesthesiology and Intensive Care, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy

    Salvatore Lucio Cutuli, Veronica Gennenzi, Joel Vargas & Gennaro De Pascale

Authors
  1. Salvatore Lucio Cutuli
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  2. Veronica Gennenzi
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  3. Joel Vargas
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  4. Gennaro De Pascale
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Correspondence to Gennaro De Pascale .

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Editors and Affiliations

  1. Anesthesia and Intensive Care, Santa Chiara Regional Hospital, APSS Trento, Centre for Medical Sciences - CISMed University of Trento, Via S. Maria Maddalena, Trento, Italy

    Silvia De Rosa

  2. Anesthesiology and Intensive Care, Dept. of Health Science, University of Florence, Firenze, Italy

    Gianluca Villa

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Cutuli, S.L., Gennenzi, V., Vargas, J., De Pascale, G. (2023). Clinical Management of Endotoxemia: Antibiotics. In: De Rosa, S., Villa, G. (eds) Endotoxin Induced-Shock: a Multidisciplinary Approach in Critical Care. Springer, Cham. https://doi.org/10.1007/978-3-031-18591-5_6

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  • DOI: https://doi.org/10.1007/978-3-031-18591-5_6

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  • Online ISBN: 978-3-031-18591-5

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