De-escalating Antibiotic Use in the Inpatient Setting: Strategies, Controversies, and Challenges

  • J. Daniel Markley
  • Shaina Bernard
  • Gonzalo Bearman
  • Michael P. Stevens
Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Healthcare Associated Infections

Abstract

Purpose of Review

Antibiotic de-escalation (ADE) is widely accepted as an integral strategy to curtail the global antibiotic resistance crisis. However, there is significant uncertainty regarding the ideal ADE strategy and its true impact on antibiotic resistance. Rapid diagnostic testing has the potential to enhance ADE strategies. Herein, we aim to discuss the current strategies, controversies, and challenges of ADE in the inpatient setting.

Recent Findings

A consensus definition of ADE remains elusive at this time. Preliminary studies utilizing rapid diagnostic tests including matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), procalcitonin, and other molecular techniques have demonstrated the potential to support ADE strategies.

Summary

In the absence of evidence-based, highly specific ADE protocols, the likelihood that individual providers will make consistent, often challenging, decisions to de-escalate antibiotic therapy is low. Antimicrobial stewardship programs should support local physicians with ADE and develop innovative ways to integrate ADE into the broader construct of antimicrobial stewardship programs. The evolving field of rapid diagnostics has significant potential to improve ADE strategies, but more research is needed to fully realize this goal.

Keywords

Antibiotic de-escalation Antimicrobial stewardship Resistance 

Notes

Compliance with Ethical Standards

Conflict of Interest

Drs Markley, Bernard, Bearman, Stevens declares no conflict of interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Antibiotic/antimicrobial resistance. centers for disease control and prevention. https://www.cdc.gov/drugresistance/. Accessed 7/19/2016, 2016.
  2. 2.
    McGann P, Snesrud E, Maybank R, et al. Escherichia coli Harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(7):4420–1. doi:10.1128/AAC.01103-16.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Core elements of hospital antibiotic stewardship programs. http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html#_ENREF_2. Updated 2016. Accessed 7/20, 2016.
  4. 4.
    Hecker MT, Aron DC, Patel NP, Lehmann MK, Donskey CJ. Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity. Arch Intern Med. 2003;163(8):972–8. doi:10.1001/archinte.163.8.972.CrossRefPubMedGoogle Scholar
  5. 5.
    Fridkin S, Baggs J, Fagan R, et al. Vital signs: improving antibiotic use among hospitalized patients. Morb Mortal Wkly Rep. 2014;63(9):194–200.Google Scholar
  6. 6.
    Antimicrobial resistance fact sheet. world health organization. http://www.who.int/mediacentre/factsheets/fs194/en/. Accessed 7/19/2016, 2016.
  7. 7.
    National action plan for combating antibiotic-resistant bacteria. https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf. Updated 2015. Accessed 07/22, 2016.
  8. 8.
    Antibiotic resistance solutions initiative. centers for disease control and prevention. https://www.cdc.gov/drugresistance/solutions-initiative/index.html. Updated 2016. Accessed 7/22, 2016.
  9. 9.
    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(10):1197–202. doi:10.1093/cid/ciw217.CrossRefPubMedGoogle Scholar
  10. 10.
    • 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(8):1009–17. doi:10.1093/cid/civ1199. This recent article provides the most up to date review of antimicrobial de-escalation as it pertains to the intensive care unit. The authors address the current evidence base, challenges, and future directions of de-escalation in the ICU. CrossRefPubMedGoogle Scholar
  11. 11.
    • Kollef MH, Micek ST. Editorial commentary: antimicrobial de-escalation: what’s in a name? Clin Infect Dis. 2016;62(8):1018–20. doi:10.1093/cid/civ1201. This editorial provides an expert analysis of the current challenges and future directions of antimicrobial de-escalation. Several key questions are posed that lend valuable insight into the current methodological flaws that are inhibiting the advancement of research in antibiotic de-escalation. CrossRefPubMedGoogle Scholar
  12. 12.
    Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637. doi:10.1097/CCM.0b013e31827e83af.CrossRefPubMedGoogle Scholar
  13. 13.
    Hummel M, Warga C, Hof H, Hehlmann R, Buchheidt D. Diagnostic yield of blood cultures from antibiotic-naïve and antibiotically treated patients with haematological malignancies and high-risk neutropenia. Scand J Infect Dis. 2009;41(9):650–5. doi:10.1080/00365540903062150.CrossRefPubMedGoogle Scholar
  14. 14.
    De Waele JJ, Ravyts M, Depuydt P, Blot SI, Decruyenaere J, Vogelaers D. De-escalation after empirical meropenem treatment in the intensive care unit: fiction or reality? J Crit Care. 2010;25(4):641–6. doi:10.1016/j.jcrc.2009.11.007.CrossRefPubMedGoogle Scholar
  15. 15.
    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(1):41–9. doi:10.1007/s00134-013-3148-9.CrossRefPubMedGoogle Scholar
  16. 16.
    Morel J, Casoetto J, Jospé R, et al. De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit. Crit Care. 2010;14(6):R225. doi:10.1186/cc9373.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    •• Masterton RG. Antibiotic de-escalation. Crit Care Clin. 2011;27(1):149–62. doi:10.1016/j.ccc.2010.09.009. This article provides the most comprehensive review of antimicrobial de-escalation. Anyone interested in developing a basic foundation in de-escalation concepts should read this article. CrossRefPubMedGoogle Scholar
  18. 18.
    Garnacho-Montero J, Escoresca-Ortega A, Fernández-Delgado E. Antibiotic de-escalation in the ICU: how is it best done? Curr Opin Infect Dis. 2015;28(2):193–8. doi:10.1097/QCO.0000000000000141.CrossRefPubMedGoogle Scholar
  19. 19.
    Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;162(2):505–11. doi:10.1164/ajrccm.162.2.9909095.CrossRefPubMedGoogle Scholar
  20. 20.
    Soo Hoo GW, Wen YE, Nguyen TV, Goetz MB. Impact of clinical guidelines in the management of severe hospital-acquired pneumonia. Chest. 2005;128(4):2778–87. doi:10.1378/chest.128.4.2778.CrossRefPubMedGoogle Scholar
  21. 21.
    Rello J, Vidaur L, Sandiumenge A, et al. De-escalation therapy in ventilator-associated pneumonia. Crit Care Med. 2004;32(11):2183–90.CrossRefPubMedGoogle Scholar
  22. 22.
    Brunkhorst FM, Heinz U, Forycki ZF. Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med. 1998;24(8):888–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Maruna P, Frasko R, Gürlich R. Plasma procalcitonin in patients with ileus. Relations to other inflammatory parameters. Physiol Res. 2008;57(3):481–6.PubMedGoogle Scholar
  24. 24.
    Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: what is useful? Crit Care Clin. 2006;22(3):503–19. ix doi:10.1016/j.ccc.2006.03.003.CrossRefPubMedGoogle Scholar
  25. 25.
    Giamarellos-Bourboulis E, Grecka P, Poulakou G, Anargyrou K, Katsilambros N, Giamarellou H. Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis. 2001;32(12):1718–25. doi:10.1086/320744.CrossRefPubMedGoogle Scholar
  26. 26.
    Li H, Luo Y, Blackwell TS, Xie C. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agents Chemother. 2011;55(12):5900–6. doi:10.1128/AAC.00335-11.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–66. doi:10.1001/jama.2009.1297.CrossRefPubMedGoogle Scholar
  28. 28.
    Nobre V, Harbarth S, Graf J, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008;177(5):498–505. doi:10.1164/rccm.200708-1238OC.CrossRefPubMedGoogle Scholar
  29. 29.
    Schroeder S, Hochreiter M, Koehler T, et al. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbeck's Arch Surg. 2009;394(2):221–6. doi:10.1007/s00423-008-0432-1.CrossRefGoogle Scholar
  30. 30.
    Hochreiter M, Köhler T, Schweiger AM, et al. Procalcitonin to guide duration of antibiotic therapy in intensive are patients: A randomized prospective controlled trial. Crit Care. 2009;13(3). doi:10.1186/cc7903.
  31. 31.
    Bouadma L, Luyt C, 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(9713):463–74. doi:10.1016/S0140-6736(09)61879-1.CrossRefPubMedGoogle Scholar
  32. 32.
    Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock–a systematic review and meta-analysis. Crit Care. 2013;17(6). doi:10.1186/cc13157.
  33. 33.
    Jensen JU, Hein L, Lundgren B, et al. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011;39(9):2048–58. doi:10.1097/CCM.0b013e31821e8791.CrossRefPubMedGoogle Scholar
  34. 34.
    Layios N, Lambermont B, Canivet J, et al. Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients. Crit Care Med. 2012;40(8):2304–9. doi:10.1097/CCM.0b013e318251517a.CrossRefPubMedGoogle Scholar
  35. 35.
    Goff DA, Jankowski C, Tenover FC. Using rapid diagnostic tests to optimize antimicrobial selection in antimicrobial stewardship programs. Pharmacotherapy. 2012;32(8):677–87. doi:10.1002/j.1875-9114.2012.01137.x.CrossRefPubMedGoogle Scholar
  36. 36.
    Carver PL, Lin S, DePestel DD, Newton DW. Impact of mecA gene testing and intervention by infectious disease clinical pharmacists on time to optimal antimicrobial therapy for Staphylococcus aureus bacteremia at a university hospital. J Clin Microbiol. 2008;46(7):2381–3. doi:10.1128/JCM.00801-08.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Perez KK, Olsen RJ, Musick WL, et al. Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs. Archives of pathology & laboratory medicine. 2013;137(9):1247–54. doi:10.5858/arpa.2012-0651-OA.CrossRefGoogle Scholar
  38. 38.
    Ly T, Gulia J, Pyrgos V, Waga M, Shoham S. Impact upon clinical outcomes of translation of PNA FISH-generated laboratory data from the clinical microbiology bench to bedside in real time. Ther Clin Risk Manag. 2008;4(3):637–40.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Huang AM, Newton D, Kunapuli A, et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis. 2013;57(9):1237–45. doi:10.1093/cid/cit498.CrossRefPubMedGoogle Scholar
  40. 40.
    Holtzman C, Whitney D, Barlam T, Miller NS. Assessment of impact of peptide nucleic acid fluorescence in situ hybridization for rapid identification of coagulase-negative staphylococci in the absence of antimicrobial stewardship intervention. J Clin Microbiol. 2011;49(4):1581–2. doi:10.1128/JCM.02461-10.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Forrest GN, Mehta S, Weekes E, Lincalis DP, Johnson JK, Venezia RA. Impact of rapid in situ hybridization testing on coagulase-negative staphylococci positive blood cultures. J Antimicrob Chemother. 2006;58(1):154–8. doi:10.1093/jac/dkl146.CrossRefPubMedGoogle Scholar
  42. 42.
    Fleming-Dutra K, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17):1864–73. doi:10.1001/jama.2016.4151.CrossRefPubMedGoogle Scholar
  43. 43.
    Gerber JS, Prasad PA, Fiks AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309(22):2345–52. doi:10.1001/jama.2013.6287.CrossRefPubMedGoogle Scholar
  44. 44.
    Get smart: Know when antibiotics work, centers for disease control and prevention. http://www.cdc.gov/getsmart/community/index.html. Updated 2015. Accessed 4/7, 2016.
  45. 45.
    Donaldson AD, Barkham T. De-escalation for amoxicillin-susceptible Escherichia coli: easier said than done. The journal of hospital infection. 2010;74(3):304–5. doi:10.1016/j.jhin.2009.07.013.CrossRefPubMedGoogle Scholar
  46. 46.
    Niederman MS, Soulountsi V. De-escalation therapy: is it valuable for the management of ventilator-associated pneumonia? Clin Chest Med. 2011;32(3):517–34. doi:10.1016/j.ccm.2011.05.009.CrossRefPubMedGoogle Scholar
  47. 47.
    2014 Physician Specialty Data Book Center for Workforce Studies. Association of American Medical Colleges. Washington, DC: AAMC; 2014; 1–42. Available at: https://members.aamc.org/eweb/upload/Physician%20Specialty%20Databook%202014.pdf. Accessed 9/9, 2016.
  48. 48.
    Chandrasekar PH. Bad news to worse news: 2015 infectious diseases fellowship match results. Clin Infect Dis. 2015;60(9). doi:10.1093/cid/civ037.
  49. 49.
    Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–27. doi:10.1056/NEJMoa1500245.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Khan AR, Khan S, Zimmerman V, Baddour LM, Tleyjeh IM. Quality and strength of evidence of the infectious diseases society of america clinical practice guidelines. Clin Infect Dis. 2010;51(10):1147–56. doi:10.1086/656735.CrossRefPubMedGoogle Scholar
  51. 51.
    Tackling drug-resistant infections globally: Final report and recommendations. http://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf. Updated 2016. Accessed 9/12, 2016.

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • J. Daniel Markley
    • 1
  • Shaina Bernard
    • 2
  • Gonzalo Bearman
    • 1
  • Michael P. Stevens
    • 1
  1. 1.Department of Internal Medicine, Division of Infectious DiseasesVirginia Commonwealth University Medical CenterRichmondUSA
  2. 2.Department of PharmacyVirginia Commonwealth University Medical CenterRichmondUSA

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