Antimicrobial Stewardship Approaches in the Intensive Care Unit

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Key points

  • Antibiotic resistance is a major and growing problem, and antimicrobials are a limited resource. Antimicrobial stewardship is an approach to improving and monitoring the use of existing antimicrobials.

  • The intensive care unit (ICU) is a unique and high-stakes setting for antimicrobial use that presents distinct challenges for antimicrobial stewardship programs. This article outlines approaches to antimicrobial stewardship with a focus on the ICU setting.

  • Opportunities for antimicrobial

Case presentations

  • A 75-year-old man who underwent a Whipple procedure for pancreatic cancer 1 month prior with a rocky postoperative course, including respiratory failure, shock, upper gastrointestinal bleed, and surgical site infection, develops a new fever, need for reintubation, and pressor requirement. Blood and urine cultures are negative and chest radiograph demonstrates bilateral infiltrates, stable from prior. How should this patient's antibiotics be managed initially? What tests are useful to help

Background

More than 2 million illnesses and 23,000 deaths occur each year in the United States due to infections caused by antimicrobial-resistant pathogens, a large burden of which occur in the intensive care unit (ICU) setting.1, 2 Since the discovery of penicillin, there has been a clear temporal relationship between the introduction of antibiotics into clinical practice and development of resistance.3 Though the antibiotic pipeline has improved in recent years, new drugs have not kept pace with

General antimicrobial stewardship approaches

Basic elements of antimicrobial stewardship programs (ASPs) include having a dedicated institutional policy, an interdisciplinary team, members (ideally both MD and PharmD degrees) with training in antimicrobial stewardship or ID, and monitoring and reporting of activities (Fig. 1). Core actions of ASPs include7, 8

  • Facility-specific guidelines based on national guidelines, local antibiogram, and formulary availability. These can be for particular syndromes such as pneumonia, individual

Diagnosis

As a corollary to the common use of inappropriate antimicrobial therapy in the ICU setting for noninfectious or nonbacterial syndromes, or treatment of colonization or contamination, more accurate and timely diagnosis of infection should result in improved antimicrobial use.18, 19 Goals of diagnostics for infection include

  • Establishing an infection as the cause of the presenting syndrome; discrimination of bacterial infection from noninfectious syndrome

  • Discrimination of bacterial from

Empirical therapy

While awaiting results of a work-up for a suspected infection, antimicrobial therapy will likely be administered to the ICU patient. Because inadequate empirical antibiotic therapy, or empirical antibiotics that do not cover the ultimate identified pathogen, accounts for an estimated 39% to 51% of excess mortality in ICU patients with various infectious syndromes, initiation of broad empirical therapy in a patient with high suspicion for infection is appropriate.15, 16, 63, 64 However,

Definitive therapy

Once the patient has been stabilized with empirical antimicrobials and diagnostic testing results return, a clinical and/or microbiological diagnosis often, though not always, can be made. At this point, goals of therapy become

  • Choosing the narrowest and most potent agent for identifying the syndrome and microbes and treating for minimal effectiveness

  • Optimizing pharmacodynamics and pharmacokinetics

  • Avoiding adverse consequences of antimicrobial use while ensuring cure of infection.

Demonstrating effectiveness

As with any quality improvement program, ASPs must track outcomes to focus efforts, demonstrate successes, and ensure no unexpected countermeasures. In general, ASPs should monitor both process and outcome measures.7 This includes measures of antimicrobial usage (eg, days of therapy) normalized to census, costs, antibiotic resistance, uptake of recommendations, and clinical outcomes such as adverse events, secondary infections, mortality, and length-of-stay.

Summary

Antimicrobial stewardship in the ICU setting can improve quality of care and decrease antimicrobial resistance without compromising patient outcomes. Though low-level evidence supports individual aspects of stewardship, there is little information about which particular interventions have the most impact.133 Two structured reviews of antimicrobial stewardship in the ICU setting have found modest benefit, though studies tend to be small and uncontrolled, with lack of emphasis on patient-centered

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References (134)

  • E.H. Ibrahim et al.

    The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting

    Chest

    (2000)
  • J.S. Faust et al.

    The past, present, and future of the centers for Medicare and Medicaid services quality measure SEP-1: the early management bundle for severe sepsis/septic shock

    Emerg Med Clin North Am

    (2017)
  • P. Montravers et al.

    Antifungal therapy for patients with proven or suspected candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

    Clin Microbiol Infect

    (2017)
  • L. Leibovici et al.

    The TREAT project: Decision support and prediction using causal probabilistic networks

    Int J Antimicrob Agents

    (2007)
  • J.C. McGregor et al.

    Impact of a computerized clinical decision support system on reducing inappropriate antimicrobial use: a randomized controlled trial

    J Am Med Inform Assoc

    (2006)
  • E. Macy et al.

    Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study

    J Allergy Clin Immunol

    (2014)
  • M.N. Jeffres et al.

    Consequences of avoiding β-lactams in patients with β-lactam allergies

    J Allergy Clin Immunol

    (2016)
  • E. Jerschow et al.

    Fatal anaphylaxis in the united states 1999-2010: temporal patterns and demographic associations

    J Allergy Clin Immunol

    (2014)
  • M.E. Arroliga et al.

    A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU

    Chest

    (2000)
  • Antibiotic/antimicrobial resistance. Available at: https://www.cdc.gov/drugresistance/about.html. Accessed March 14,...
  • J. Carlet et al.

    Epidemiology and control of antibiotic resistance in the intensive care unit

    Curr Opin Infect Dis

    (2004)
  • S.R. Palumbi

    Humans as the world's greatest evolutionary force

    Science

    (2001)
  • The critical need for new antibiotics. Available at:...
  • World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and...
  • Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2013. 2013....
  • T.F. Barlam et al.

    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)
  • Core elements of hospital antibiotic stewardship programs. Available at:...
  • J.E. McGowan et al.

    Effects of monitoring the usage of antibiotics: an interhospital comparison

    South Med J

    (1976)
  • J.E. McGowan et al.

    Usage of antibiotics in a general hospital: Effect of requiring justification

    J Infect Dis

    (1974)
  • California senate bill 1311....
  • Medicare and Medicaid programs; hospital and critical access hospital (CAH) changes to promote innovation, flexibility, and improvement in patient care; proposed rule

    Fed Regist

    (2016)
  • R.R. Roberts et al.

    Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship

    Clin Infect Dis

    (2009)
  • E.P. Hyle et al.

    Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection

    Arch Intern Med

    (2005)
  • M. Leone et al.

    Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome

    Crit Care Med

    (2003)
  • M. Tumbarello et al.

    Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-{beta}-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment

    Antimicrob Agents Chemother

    (2007)
  • A. Cusini et al.

    Different patterns of inappropriate antimicrobial use in surgical and medical units at a tertiary care hospital in Switzerland: a prevalence survey

    PLoS One

    (2010)
  • M.T. Hecker et al.

    Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity

    Arch Intern Med

    (2003)
  • J.P. Metlay et al.

    Antibiotic prescribing decisions of generalists and infectious disease specialists: thresholds for adopting new drug therapies

    Med Decis Making

    (2002)
  • D.N. Gilbert

    Influence of an infectious diseases specialist on ICU multidisciplinary rounds

    Crit Care Res Pract

    (2014)
  • P. Schuetz et al.

    Using procalcitonin-guided algorithms to improve antimicrobial therapy in ICU patients with respiratory infections and sepsis

    Curr Opin Crit Care

    (2013)
  • R.J. Langley et al.

    Integrative “Omic” analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes

    Am J Respir Crit Care Med

    (2014)
  • D.M. Maslove et al.

    Identification of sepsis subtypes in critically ill adults using gene expression profiling

    Crit Care

    (2012)
  • L. McHugh et al.

    A molecular host response assay to discriminate between sepsis and infection-negative systemic inflammation in critically ill patients: discovery and validation in independent cohorts

    PLoS Med

    (2015)
  • A.K. Zaas et al.

    A host-based RT-PCR gene expression signature to identify acute respiratory viral infection

    Sci Transl Med

    (2013)
  • N. Fabregas et al.

    Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies

    Thorax

    (1999)
  • M. Klompas

    Does this patient have ventilator-associated pneumonia?

    JAMA

    (2007)
  • J. Pugin et al.

    Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid

    Am Rev Respir Dis

    (1991)
  • M.D. Zilberberg et al.

    Ventilator-associated pneumonia: the clinical pulmonary infection score as a surrogate for diagnostics and outcome

    Clin Infect Dis

    (2010)
  • M. Fartoukh et al.

    Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited

    Am J Respir Crit Care Med

    (2003)
  • N. Singh et al.

    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)
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    Disclosure Statement: SBD has received research funding from Merck, Genentech, Cerexa, and Cubist Pharmaceuticals and serves as a consultant to Actelion. HFC has received grant support from Allergan and Genentech.

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