An approach to antibiotic treatment in patients with sepsis

María Luisa Martínez, Erika P Plata-Menchaca, Juan Carlos Ruiz-Rodríguez, Ricard Ferrer, María Luisa Martínez, Erika P Plata-Menchaca, Juan Carlos Ruiz-Rodríguez, Ricard Ferrer

Abstract

Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, which is time-dependent and associated with unacceptably high mortality. Thus, when treating suspicious or confirmed cases of sepsis, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Optimizing antibiotic use is essential to ensure successful outcomes and to reduce adverse antibiotic effects, as well as preventing drug resistance. All likely pathogens involved should be considered to provide an appropriate antibiotic coverage. Clinicians must investigate on the previous risk of multidrug-resistant (MDR) pathogens, and the principle of individualized dosing should replace the principle of standard dosing. The loading dose is an initial higher dose of an antibiotic for all patients, yet an individualized treatment approach for further doses should be implemented according to pharmacokinetics (PK)/pharmacodynamics (PD) and the presence of renal/liver dysfunction. Extended or continuous infusion of beta-lactams and therapeutic drug monitoring (TDM) can help to achieve therapeutic levels of antimicrobials. Reevaluation of duration and appropriateness of treatment at regular intervals are also necessary. De-escalation and shortened courses of antimicrobials must be considered for most patients, except in some justified circumstances. Leadership, teamwork, antimicrobial stewardship (AS) frameworks, guideline's recommendations on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help us to improve patients' quality of care.

Keywords: Sepsis; antimicrobial stewardship (AS); antimicrobial therapy; de-escalation; early antibiotics; early antimicrobial therapy in sepsis; sepsis treatment; septic shock; timing.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

2020 Journal of Thoracic Disease. All rights reserved.

Figures

Figure 1
Figure 1
Practice peals for antibiotic treatment in sepsis. MICs, minimum inhibitory concentrations. PD, pharmacodynamics; PK, pharmacokinetics.

References

    1. Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA 2018;319:62-75. 10.1001/jama.2017.17687
    1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:801-10. 10.1001/jama.2016.0287
    1. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 2016;193:259-72. 10.1164/rccm.201504-0781OC
    1. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111-24. 10.1056/NEJMoa071366
    1. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012;366:2055-64. 10.1056/NEJMoa1202290
    1. Plata-Menchaca EP, Ferrer R. Life-support tools for improving performance of the Surviving Sepsis Campaign Hour-1 bundle. Med Intensiva 2018;42:547-50. 10.1016/j.medin.2018.07.008
    1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304-77. 10.1007/s00134-017-4683-6
    1. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med 2018;44:925-8. 10.1007/s00134-018-5085-0
    1. 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;42:1749-55. 10.1097/CCM.0000000000000330
    1. Liu VX, Fielding-Singh V, Greene JD, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017;196:856-63. 10.1164/rccm.201609-1848OC
    1. 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;34:1589-96. 10.1097/01.CCM.0000217961.75225.E9
    1. Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;136:1237-48. 10.1378/chest.09-0087
    1. Singer M. Antibiotics for sepsis: does each hour really count, or is it incestuous amplification? Am J Respir Crit Care Med 2017;196:800-2. 10.1164/rccm.201703-0621ED
    1. Bernhard M, Lichtenstern C, Eckmann C, et al. The early antibiotic therapy in septic patients--milestone or sticking point? Crit Care 2014;18:671. 10.1186/s13054-014-0671-1
    1. Mi MY, Klompas M, Evans L. Early administration of antibiotics for suspected sepsis. N Engl J Med 2019;380:593-6. 10.1056/NEJMclde1809210
    1. Beumier M, Casu GS, Hites M, et al. Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients. Minerva Anestesiol 2015;81:497-506.
    1. O’Neill J. Antimicrobial Resistance: tackling a Crisis for the Health and Wealth of Nations. 2014. Available online:
    1. Ulldemolins M, Nuvials X, Palomar M, et al. Appropriateness is critical. Crit Care Clin 2011;27:35-51. 10.1016/j.ccc.2010.09.007
    1. Gerding DN. The search for good antimicrobial stewardship. Jt Comm J Qual Improv 2001;27:403-4. 10.1016/S1070-3241(01)27034-5
    1. Joseph J, Rodvold KA. The role of carbapenems in the treatment of severe nosocomial respiratory tract infections. Expert Opin Pharmacother 2008;9:561-75. 10.1517/14656566.9.4.561
    1. Barochia AV, Cui X, Vitberg D, et al. Bundled care for septic shock: an analysis of clinical trials. Crit Care Med 2010;38:668-78. 10.1097/CCM.0b013e3181cb0ddf
    1. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med 2015;43:3-12. 10.1097/CCM.0000000000000723
    1. Coz Yataco A, Jaehne AK, Rivers EP. Protocolized early sepsis care is not only helpful for patients: it prevents medical errors. Crit Care Med 2017;45:464-72. 10.1097/CCM.0000000000002237
    1. Centers for Medicare & Medicaid Services. Fact sheet: CMS to improve quality of care during hospital inpatient stays. 2014. Available online:
    1. Dwyer J. One Boy’s Death moves state to action to prevent others. The New York Times Company. 2012. Available online:
    1. Buchman TG, Azoulay E. Practice guidelines as implementation science: the journal editors' perspective. Intensive Care Med 2017;43:378-9. 10.1007/s00134-017-4680-9
    1. Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 2006;43:25-31. 10.1086/504810
    1. Bodey GP, Jadeja L, Elting L. Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med 1985;145:1621-9. 10.1001/archinte.1985.00360090089015
    1. Garnacho-Montero J, Garcia-Cabrera E, Diaz-Martin A, et al. Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment. Scand J Infect Dis 2010;42:185-92. 10.3109/00365540903418522
    1. Gacouin A, Le Tulzo Y, Lavoue S, et al. Severe pneumonia due to Legionella pneumophila: prognostic factors, impact of delayed appropriate antimicrobial therapy. Intensive Care Med 2002;28:686-91. 10.1007/s00134-002-1304-8
    1. Hamandi B, Holbrook AM, Humar A, et al. Delay of adequate empiric antibiotic therapy is associated with increased mortality among solid-organ transplant patients. Am J Transplant 2009;9:1657-65. 10.1111/j.1600-6143.2009.02664.x
    1. Harmankaya M, Oreskov JO, Burcharth J, et al. The impact of timing of antibiotics on in-hospital outcomes after major emergency abdominal surgery. Eur J Trauma Emerg Surg 2020;46:221-7. 10.1007/s00068-018-1026-4
    1. Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med 2010;38:1045-53. 10.1097/CCM.0b013e3181cc4824
    1. Puskarich MA, Trzeciak S, Shapiro NI, et al. Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med 2011;39:2066-71. 10.1097/CCM.0b013e31821e87ab
    1. Sherwin R, Winters ME, Vilke GM, et al. Does Early and Appropriate Antibiotic Administration Improve Mortality in Emergency Department Patients with Severe Sepsis or Septic Shock? J Emerg Med 2017;53:588-95. 10.1016/j.jemermed.2016.12.009
    1. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376:2235-44. 10.1056/NEJMoa1703058
    1. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014;42:2409-17. 10.1097/CCM.0000000000000509
    1. Whiles BB, Deis AS, Simpson SQ. Increased Time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med 2017;45:623-9. 10.1097/CCM.0000000000002262
    1. Kim RY, Ng AM, Persaud AK, et al. Antibiotic timing and outcomes in sepsis. Am J Med Sci 2018;355:524-9. 10.1016/j.amjms.2018.02.007
    1. Peltan ID, Brown SM, Bledsoe JR, et al. ED door-to-antibiotic time and long-term mortality in sepsis. Chest 2019;155:938-46. 10.1016/j.chest.2019.02.008
    1. Bloos F, Ruddel H, Thomas-Ruddel D, et al. Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial. Intensive Care Med 2017;43:1602-12. 10.1007/s00134-017-4782-4
    1. Zhang D, Micek ST, Kollef MH. Time to appropriate antibiotic therapy is an independent determinant of postinfection ICU and hospital lengths of stay in patients with sepsis. Crit Care Med 2015;43:2133-40. 10.1097/CCM.0000000000001140
    1. Iscimen R, Cartin-Ceba R, Yilmaz M, et al. Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med 2008;36:1518-22. 10.1097/CCM.0b013e31816fc2c0
    1. Bagshaw SM, Lapinsky S, Dial S, et al. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 2009;35:871-81. 10.1007/s00134-008-1367-2
    1. Garnacho-Montero J, Aldabo-Pallas T, Garnacho-Montero C, et al. Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis. Crit Care 2006;10:R111. 10.1186/cc4995
    1. Hwang SY, Shin J, Jo IJ, et al. Delayed antibiotic therapy and organ dysfunction in critically ill septic patients in the emergency department. J Clin Med 2019. doi: .10.3390/jcm8020222
    1. Labelle A, Juang P, Reichley R, et al. The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment*. Crit Care Med 2012;40:2016-21. 10.1097/CCM.0b013e318250aa72
    1. de Groot B, Ansems A, Gerling DH, et al. The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study. Crit Care 2015;19:194. 10.1186/s13054-015-0936-3
    1. van Paridon BM, Sheppard C, G GG, et al. Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care. Crit Care 2015;19:293. 10.1186/s13054-015-1010-x
    1. Creedon JK, Vargas S, Asaro LA, et al. Timing of antibiotic administration in pediatric sepsis. Pediatr Emerg Care 2018. [Epub ahead of print]. 10.1097/PEC.0000000000001663
    1. Alam N, Oskam E, Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med 2018;6:40-50. 10.1016/S2213-2600(17)30469-1
    1. Sterling SA, Miller WR, Pryor J, et al. The Impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med 2015;43:1907-15. 10.1097/CCM.0000000000001142
    1. Johnston ANB, Park J, Doi SA, et al. Effect of immediate administration of antibiotics in patients with sepsis in tertiary care: a systematic review and meta-analysis. Clin Ther 2017;39:190-202.e6. 10.1016/j.clinthera.2016.12.003
    1. Laupland KB, Ferrer R. Is it time to implement door-to-needle time for "infection attacks"? Intensive Care Med 2017;43:1712-3. 10.1007/s00134-017-4797-x
    1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61-111. 10.1093/cid/ciw353
    1. IDSA Sepsis Task Force. Infectious Diseases Society of America (IDSA) position statement: why IDSA did not endorse the Surviving Sepsis Campaign Guidelines. Clin Infect Dis 2018;66:1631-5. 10.1093/cid/cix997
    1. Klompas M, Calandra T, Singer M. Antibiotics for sepsis-finding the equilibrium. JAMA 2018;320:1433-4. 10.1001/jama.2018.12179
    1. Marik PE, Farkas JD. The changing paradigm of sepsis: early diagnosis, early antibiotics, early pressors, and early adjuvant treatment. Crit Care Med 2018;46:1690-2. 10.1097/CCM.0000000000003310
    1. 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;315:762-74. 10.1001/jama.2016.0288
    1. Filbin MR, Thorsen JE, Zachary TM, et al. Antibiotic delays and feasibility of a 1-hour-from-triage antibiotic requirement: analysis of an emergency department sepsis quality improvement database. Ann Emerg Med 2020;75:93-9. 10.1016/j.annemergmed.2019.07.017
    1. Amaral AC, Fowler RA, Pinto R, et al. Patient and organizational factors associated with delays in antimicrobial therapy for septic shock. Crit Care Med 2016;44:2145-53. 10.1097/CCM.0000000000001868
    1. Peltan ID, Mitchell KH, Rudd KE, et al. Prehospital care and emergency department door-to-antibiotic time in sepsis. Ann Am Thorac Soc 2018;15:1443-50. 10.1513/AnnalsATS.201803-199OC
    1. Vattanavanit V, Buppodom T, Khwannimit B. Timing of antibiotic administration and lactate measurement in septic shock patients: a comparison between hospital wards and the emergency department. Infect Drug Resist 2018;11:125-32. 10.2147/IDR.S155099
    1. Petit J, Passerieux J, Maître O, et al. Impact of a qSOFA-based triage procedure on antibiotic timing in ED patients with sepsis: a prospective interventional study. Am J Emerg Med 2019. [Epub ahead of print]. 10.1016/j.ajem.2019.05.022
    1. Ferrer R, Martinez ML, Goma G, et al. Improved empirical antibiotic treatment of sepsis after an educational intervention: the ABISS-Edusepsis study. Crit Care 2018;22:167. 10.1186/s13054-018-2091-0
    1. Kim M, Song KH, Kim CJ, et al. Electronic alerts with automated consultations promote appropriate antimicrobial prescriptions. PLoS One 2016;11:e0160551. 10.1371/journal.pone.0160551
    1. Micek ST, Heard KM, Gowan M, et al. Identifying critically ill patients at risk for inappropriate antibiotic therapy: a pilot study of a point-of-care decision support alert. Crit Care Med 2014;42:1832-8. 10.1097/CCM.0000000000000337
    1. Barlam TF, Cosgrove SE, Abbo LM, et al. Executive summary: implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:1197-202. 10.1093/cid/ciw217
    1. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality. Crit Care 2015;19:302. 10.1186/s13054-015-1000-z
    1. Walsh D, Gekle R, Bramante R, et al. Emergency department sepsis huddles: Achieving excellence for sepsis benchmarks in New York State. Am J Emerg Med 2019. [Epub ahead of print]. 10.1016/j.ajem.2019.02.007
    1. Hitti EA, Lewin JJ, 3rd, Lopez J, et al. Improving door-to-antibiotic time in severely septic emergency department patients. J Emerg Med 2012;42:462-9. 10.1016/j.jemermed.2011.05.015
    1. Kufel WD, Seabury RW, Meola GM, et al. Impact of premix antimicrobial preparation and time to administration in septic patients. CJEM 2018;20:565-71. 10.1017/cem.2017.33
    1. Vallés J, Rello J, Ochagavía A, et al. Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival. Chest 2003;123:1615-24. 10.1378/chest.123.5.1615
    1. Suberviola Cañas B, Jáuregui R, Ballesteros MÁ, et al. Effects of antibiotic administration delay and inadequacy upon the survival of septic shock patients. Med Intensiva 2015;39:459-66.
    1. Zilberberg MD, Shorr AF, Micek ST, et al. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 2014;18:596. 10.1186/s13054-014-0596-8
    1. Vazquez-Guillamet C, Scolari M, Zilberberg MD, et al. Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock. Crit Care Med 2014;42:2342-9. 10.1097/CCM.0000000000000516
    1. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, et al. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 2003;31:2742-51. 10.1097/01.CCM.0000098031.24329.10
    1. Battleman DS, Callahan M, Thaler HT. Rapid antibiotic delivery and appropriate antibiotic selection reduce length of hospital stay of patients with community-acquired pneumonia: link between quality of care and resource utilization. Arch Intern Med 2002;162:682-8. 10.1001/archinte.162.6.682
    1. Green RS, Gorman SK. Emergency department antimicrobial considerations in severe sepsis. Emerg Med Clin North Am 2014;32:835-49. 10.1016/j.emc.2014.07.014
    1. Pogue JM, Mynatt RP, Marchaim D, et al. Automated alerts coupled with antimicrobial stewardship intervention lead to decreases in length of stay in patients with gram-negative bacteremia. Infect Control Hosp Epidemiol 2014;35:132-8. 10.1086/674849
    1. Vincent JL, Bassetti M, Francois B, et al. Advances in antibiotic therapy in the critically ill. Crit Care 2016;20:133. 10.1186/s13054-016-1285-6
    1. Coopersmith CM, De Backer D, Deutschman CS, et al. Surviving Sepsis Campaign: research priorities for sepsis and septic shock. Crit Care Med 2018;46:1334-56. 10.1097/CCM.0000000000003225
    1. Díaz-Martín A, Martínez-González ML, Ferrer R, et al. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality. Crit Care 2012;16:R223. 10.1186/cc11869
    1. Martin-Loeches I, Lisboa T, Rodriguez A, et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med 2010;36:612-20. 10.1007/s00134-009-1730-y
    1. Al-Hasan MN, Wilson JW, Lahr BD, et al. Beta-lactam and fluoroquinolone combination antibiotic therapy for bacteremia caused by gram-negative bacilli. Antimicrob Agents Chemother 2009;53:1386-94. 10.1128/AAC.01231-08
    1. Delannoy PY, Boussekey N, Devos P, et al. Impact of combination therapy with aminoglycosides on the outcome of ICU-acquired bacteraemias. Eur J Clin Microbiol Infect Dis 2012;31:2293-9. 10.1007/s10096-012-1568-z
    1. Micek ST, Welch EC, Khan J, et al. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob Agents Chemother 2010;54:1742-8. 10.1128/AAC.01365-09
    1. Kumar A, Safdar N, Kethireddy S, et al. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med 2010;38:1651-64. 10.1097/CCM.0b013e3181e96b91
    1. Kumar A, Zarychanski R, Light B, et al. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 2010;38:1773-85. 10.1097/CCM.0b013e3181eb3ccd
    1. Brunkhorst FM, Oppert M, Marx G, et al. Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA 2012;307:2390-9. 10.1001/jama.2012.5833
    1. Paul M, Lador A, Grozinsky-Glasberg S, et al. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014;(1):CD003344.
    1. Ong DSY, Frencken JF, Klein Klouwenberg PMC, et al. Short-course adjunctive gentamicin as empirical therapy in patients with severe sepsis and septic shock: a prospective observational cohort study. Clin Infect Dis 2017;64:1731-6. 10.1093/cid/cix186
    1. Septimus EJ, Coopersmith CM, Whittle J, et al. Sepsis national hospital inpatient quality measure (SEP-1): multistakeholder work group recommendations for appropriate antibiotics for the treatment of sepsis. Clin Infect Dis 2017;65:1565-9. 10.1093/cid/cix603
    1. Klompas M. Monotherapy is adequate for septic shock due to gram-negative organisms. Crit Care Med 2017;45:1930-2. 10.1097/CCM.0000000000002678
    1. Turza KC, Politano AD, Rosenberger LH, et al. De-escalation of antibiotics does not increase mortality in critically ill surgical patients. Surg Infect (Larchmt) 2016;17:48-52. 10.1089/sur.2014.202
    1. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 2014;40:32-40. 10.1007/s00134-013-3077-7
    1. Tabah A, Cotta MO, Garnacho-Montero J, et al. A Systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clin Infect Dis 2016;62:1009-17. 10.1093/cid/civ1199
    1. Gutiérrez-Pizarraya A, Leone M, Garnacho-Montero J, et al. Collaborative approach of individual participant data of prospective studies of de-escalation in non-immunosuppressed critically ill patients with sepsis. Expert Rev Clin Pharmacol 2017;10:457-65. 10.1080/17512433.2017.1293520
    1. Mokart D, Slehofer G, Lambert J, et al. De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 2014;40:41-9. 10.1007/s00134-013-3148-9
    1. Leone M, Bechis C, Baumstarck K, et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 2014;40:1399-408. 10.1007/s00134-014-3411-8
    1. van den Bosch CM, Hulscher ME, Natsch S, et al. Development of quality indicators for antimicrobial treatment in adults with sepsis. BMC Infect Dis 2014;14:345. 10.1186/1471-2334-14-345
    1. Hayashi Y, Paterson DL. Strategies for reduction in duration of antibiotic use in hospitalized patients. Clin Infect Dis 2011;52:1232-40. 10.1093/cid/cir063
    1. Niederman MS, Soulountsi V. De-escalation therapy: is it valuable for the management of ventilator-associated pneumonia? Clin Chest Med 2011;32:517-34. 10.1016/j.ccm.2011.05.009
    1. Esteban E, Belda S, Garcia-Soler P, et al. A multifaceted educational intervention shortened time to antibiotic administration in children with severe sepsis and septic shock: ABISS Edusepsis pediatric study. Intensive Care Med 2017;43:1916-8. 10.1007/s00134-017-4721-4
    1. Cheng MP, Stenstrom R, Paquette K, et al. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis: a diagnostic study. Ann Intern Med 2019. [Epub ahead of print]. 10.7326/M19-1696
    1. Richter DC, Heininger A, Brenner T, et al. Bacterial sepsis: diagnostics and calculated antibiotic therapy. Anaesthesist 2019;68:40-62. 10.1007/s00101-017-0396-z
    1. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003;290:2588-98. 10.1001/jama.290.19.2588
    1. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med 2015;372:1996-2005. 10.1056/NEJMoa1411162
    1. Hepburn MJ, Dooley DP, Skidmore PJ, et al. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med 2004;164:1669-74. 10.1001/archinte.164.15.1669
    1. el Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ 2006;332:1355. 10.1136/bmj.332.7554.1355
    1. Zilahi G, McMahon MA, Povoa P, et al. Duration of antibiotic therapy in the intensive care unit. J Thorac Dis 2016;8:3774-80. 10.21037/jtd.2016.12.89
    1. Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev 2015;(8):CD007577.
    1. Chotiprasitsakul D, Han JH, Cosgrove SE, et al. Comparing the outcomes of adults with Enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score-matched cohort. Clin Infect Dis 2018;66:172-7. 10.1093/cid/cix767
    1. Cabellos C, Pelegrin I, Benavent E, et al. Invasive meningococcal disease: impact of short course therapy. A DOOR/RADAR study. J Infect 2017;75:420-5. 10.1016/j.jinf.2017.08.009
    1. Martínez ML, Ferrer R, Torrents E, et al. Impact of source control in patients with severe sepsis and septic shock. Crit Care Med 2017;45:11-9. 10.1097/CCM.0000000000002011
    1. Saeed K, Gonzalez Del Castillo J, Backous C, et al. Hot topics on procalcitonin use in clinical practice, can it help antibiotic stewardship? Int J Antimicrob Agents 2019;54:686-96. 10.1016/j.ijantimicag.2019.07.016
    1. de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16:819-27. 10.1016/S1473-3099(16)00053-0
    1. Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med 2018;379:236-49. 10.1056/NEJMoa1802670
    1. Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010;375:463-74. 10.1016/S0140-6736(09)61879-1
    1. Sager R, Kutz A, Mueller B, et al. Procalcitonin-guided diagnosis and antibiotic stewardship revisited. BMC Med 2017;15:15. 10.1186/s12916-017-0795-7
    1. Jung B, Molinari N, Nasri M, et al. Procalcitonin biomarker kinetics fails to predict treatment response in perioperative abdominal infection with septic shock. Crit Care 2013;17:R255. 10.1186/cc13082
    1. Garcia IJ, Gargallo MB, Torne EE, et al. Procalcitonin: a useful biomarker to discriminate infection after cardiopulmonary bypass in children. Pediatr Crit Care Med 2012;13:441-5. 10.1097/PCC.0b013e31823890de
    1. Oliveira CF, Botoni FA, Oliveira CR, et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med 2013;41:2336-43. 10.1097/CCM.0b013e31828e969f
    1. Iankova I, Thompson-Leduc P, Kirson NY, et al. Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis: a systematic review and meta-analysis. Crit Care Med 2018;46:691-8. 10.1097/CCM.0000000000002928
    1. Roberts JA, Roger C, De Waele JJ. Personalized antibiotic dosing for the critically ill. Intensive Care Med 2019;45:715-8. 10.1007/s00134-019-05522-3
    1. Ulldemolins M, Roberts JA, Lipman J, et al. Antibiotic dosing in multiple organ dysfunction syndrome. Chest 2011;139:1210-20. 10.1378/chest.10-2371
    1. Veiga RP, Paiva JA. Pharmacokinetics-pharmacodynamics issues relevant for the clinical use of beta-lactam antibiotics in critically ill patients. Crit Care 2018;22:233. 10.1186/s13054-018-2155-1
    1. Roberts JA, Taccone FS, Lipman J. Understanding PK/PD. Intensive Care Med 2016;42:1797-800. 10.1007/s00134-015-4032-6
    1. Roberts JA, Lipman J. Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet 2006;45:755-73. 10.2165/00003088-200645080-00001
    1. Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care 2015;19:28. 10.1186/s13054-015-0750-y
    1. Huttner A, Von Dach E, Renzoni A, et al. Augmented renal clearance, low beta-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents 2015;45:385-92. 10.1016/j.ijantimicag.2014.12.017
    1. Carlier M, Carrette S, Roberts JA, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit Care 2013;17:R84. 10.1186/cc12705
    1. Roberts JA, Ulldemolins M, Roberts MS, et al. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents 2010;36:332-9. 10.1016/j.ijantimicag.2010.06.008
    1. Taccone FS, Laterre PF, Dugernier T, et al. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 2010;14:R126. 10.1186/cc9091
    1. De Backer D, Cecconi M, Lipman J, et al. Challenges in the management of septic shock: a narrative review. Intensive Care Med 2019;45:420-33. 10.1007/s00134-019-05544-x
    1. Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 2014;58:1072-83. 10.1093/cid/ciu027
    1. Abdul-Aziz MH, Lipman J, Akova M, et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the defining antibiotic levels in intensive care unit patients (DALI) cohort. J Antimicrob Chemother 2016;71:196-207. 10.1093/jac/dkv288
    1. Falagas ME, Tansarli GS, Ikawa K, et al. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis 2013;56:272-82. 10.1093/cid/cis857
    1. Roberts JA, Abdul-Aziz MH, Davis JS, et al. Continuous versus intermittent beta-lactam infusion in severe sepsis. A meta-analysis of individual patient data from randomized trials. Am J Respir Crit Care Med 2016;194:681-91. 10.1164/rccm.201601-0024OC
    1. Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal beta-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis 2018;18:108-20. 10.1016/S1473-3099(17)30615-1
    1. Hanrahan T, Whitehouse T, Lipman J, et al. Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion. Int J Antimicrob Agents 2015;46:249-53. 10.1016/j.ijantimicag.2015.04.013
    1. Taubert M, Zander J, Frechen S, et al. Optimization of linezolid therapy in the critically ill: the effect of adjusted infusion regimens. J Antimicrob Chemother 2017;72:2304-10. 10.1093/jac/dkx149
    1. Dulhunty JM, Roberts JA, Davis JS, et al. A multicenter randomized trial of continuous versus intermittent beta-lactam infusion in severe sepsis. Am J Respir Crit Care Med 2015;192:1298-305. 10.1164/rccm.201505-0857OC

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren