Michael S. Pulia, MD, MSa; Robert Redwood, MD, MPHb; Brian Sharp, MDc
a Emergency Medicine Antimicrobial Stewardship Program, BerbeeWalsh Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, 800 University Bay Drive, Suite 310, Madison, WI 53705, USA
b Antibiotic Stewardship Committee, Divine Savior Healthcare, 2817 New Pinery Road, Portage, WI 53901, USA
c The American Center, BerbeeWalsh Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, 800 University Bay Drive, Suite 310, Madison, WI 53705, USA
Keywords
Antimicrobial stewardship; Antibiotics; Sepsis; Clinical decision support; Biomarkers; Rapid pathogen identification assays; Quality measures; Emergency medicine
Key points
- Antimicrobial stewardship refers to efforts aimed at enhancing judicious prescribing of these unique therapeutic agents in health care settings.
- Inappropriate use of antimicrobials represents a global threat to public health and a direct threat to individual patient safety.
- Sepsis is a life-threatening, complex clinical syndrome without a gold standard diagnostic test and thus represents a unique clinical dilemma with regard to antimicrobial stewardship.
- Recent literature questioning the clinical impact of time to antimicrobials in sepsis before the onset of shock and improving the definition of sepsis may have a positive impact on antimicrobial stewardship.
- Electronic health record clinical decision support, biomarkers, and rapid pathogen identification assays have tremendous potential to enhance antimicrobial stewardship in sepsis care and should be a focus of future research efforts.
Introduction
The term antimicrobial stewardship is often mistakenly considered to only include efforts to reduce or restrict use of these agents. A more comprehensive view includes a focus on the “4 Ds” of optimal antimicrobial therapy coined by Joseph and Rodvold
1 in 2008: drug, dose, de-escalation, and duration. The focus here is on getting the right antimicrobial in the right dose to the right patient for the right amount of time. The opposite of optimal antimicrobial therapy is often referred to as inappropriate or overuse. These terms can refer to a range of practices, such as prescribing when no antimicrobial was indicated, prescribing an overly broad-spectrum agent, or prescribing an excessive length of therapy. In some instances, such as bronchitis, the right antimicrobial is no antimicrobial. In cases of septic shock, the right antimicrobial is broad-spectrum coverage of all likely pathogens. Both of these scenarios represent widely accepted approaches to antimicrobial stewardship. Unfortunately, when it comes to suspected sepsis in the emergency department (ED) setting, the ideal approach to the antimicrobial management is less clear.
The timely administration of antimicrobial agents with activity against the causative pathogen has been a cornerstone of sepsis management long before it was included in the original Surviving Sepsis consensus guidelines.
2 Based on the literature linking time and appropriateness of antimicrobials to mortality in sepsis,
3, 4, 5, 6 and 7 the ED implementation of this concept has been to rapidly cover all potential pathogens with broad-spectrum agents. De-escalation of therapy is left to occur days later after the patient has stabilized or when pathogen information is available.
The problem with this approach stems from a lack of a true gold standard for diagnosing the complex syndrome that is sepsis and the corresponding inaccuracy of widely used diagnostic criteria. The Sepsis 2.0 definition of 2 systemic inflammatory response syndrome (SIRS) criteria plus suspected infection suffers from poor discriminant validity due to a lack of specificity for both infection and the occurrence of adverse outcomes.8, 9 and 10 The combination of flawed diagnostic criteria with incredible time pressure to provide broad-spectrum antimicrobial therapy is troubling from the stewardship perspective, as it is not uncommon for patients with otherwise uncomplicated cases of common infections (eg, influenza, pneumonia, or pyelonephritis) to meet this widely used definition of sepsis.
Emerging literature that questions the optimal timing and clinical impact of antimicrobial agents in sepsis before the onset of shock may relax some of the pressure on emergency providers and allow more judicious and targeted administration in response to clinical judgment and patient trajectory rather than rigid definitions.11, 12, 13 and 14 Also, recently updated definitions of sepsis and septic shock appear to offer an improved ability to identify septic patients at risk for adverse outcomes and thus most likely in need of early broad-spectrum antimicrobials.9 and 15 As these definitions were developed with hospital mortality as the primary outcome variable,15 their value as broad screening tools for sepsis in the ED and impact on antimicrobial stewardship will require further study. Unfortunately, these promising developments for antimicrobial stewardship in sepsis exist in sharp contrast to the recently implemented Centers for Medicare and Medicaid Services (CMS) ED Sepsis Quality Measure, which codifies poor performing and outdated definitions of sepsis and links them to mandated use of a specific list of broad-spectrum agents.
The discussion around more judicious use of antimicrobials in sepsis also must include data that suggest that up to 30% of patients diagnosed with sepsis in US EDs do not receive antibiotics before admission.16 There is clearly much work to be done in both defining what constitutes optimal antimicrobial use in sepsis and the development of implementation strategies that facilitate their appropriate administration. The aim of this article was to provide an overview of antimicrobial resistance, evidence-based antimicrobial stewardship interventions for the ED, and potential future directions with regard to antimicrobial use in sepsis care. Due to a paucity of interventional research aimed at improving antimicrobial use in sepsis, aside from enhancing time to administration, much of this information is gleaned from interventional ED stewardship research involving other types of infection.
Public health implications of antimicrobial overuse
Antimicrobial resistance is a naturally occurring phenomenon in which antimicrobials exert selective pressure on pathogens that, in turn, develop defense mechanisms against that antimicrobial agent’s mode of attack.17 Overuse and misuse of antimicrobials has accelerated this natural process, resulting in multidrug-resistant organisms or “super bugs,” as well as a general trend toward antimicrobial resistance outpacing humankind’s ability to develop novel, effective antimicrobials.18
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