ICUs are arguably the most important yet most challenging hospital environments for antimicrobial stewardship. The stakes are high with critically ill patients, where the burden of resistant Gram-negative pathogens is greater and associated with poor clinical outcomes (1). It is estimated that 70% of patients receive antibiotics during an ICU stay; however, half of these antibiotics are continued for over 72 hours in the absence of a diagnosis of an infection and 30–50% of these antibiotics are considered inappropriate based on a lack of infection, excessively broad spectrum of activity, or prolonged duration of use (2–4). This is not surprising, since there is significant overlap between the presentation of noninfectious and infectious clinical syndromes. Additionally, it is challenging to fight clinical inertia and stop antibiotics in the absence of an infectious diagnosis or determine duration of therapy when an infectious diagnosis remains unclear especially in the face of clinical improvement.
The goal of antimicrobial stewardship in ICUs should be to get the right drug, dose, route, and frequency at the right time, while limiting the negative consequences of antibiotic overuse and misuse, such as Clostridioides difficile, multidrug-resistant organisms, and antibiotic-associated toxicity. For the critically ill patient, this creates two sides of the coin for antimicrobial stewardship activity: 1) ensuring timely, effective antibiotic prescription and 2) limiting unnecessary antibiotic prescription. Ensuring effective antibiotic prescription includes prompt administration of broad-spectrum antibiotics for patients with septic shock, escalation of empiric antibiotic therapy in patients at high-risk of multidrug-resistant organisms, and implementing effective dosing strategies (e.g., extended infusions for beta-lactams). Limiting unnecessary antibiotic prescription includes deescalating therapy based on available culture data or clinical context and limiting use to the shortest duration possible, while minimizing unnecessary exposure among patients who do not need antibiotics altogether.
The prospective audit and feedback mechanism is an effective strategy used by antimicrobial stewardship teams in the hospital (5). Antimicrobial prescriptions are reviewed by the antimicrobial stewardship team, typically 48–72 hours after antimicrobial initiation, with recommendations given directly to the patient care team. Many quasi-experimental studies evaluating the effect of audit and feedback on antimicrobial use in ICUs have identified positive outcomes including decreased antibiotic utilization, decreased antibiotic resistance rates, and decreased rates of C. difficile infection (6–8). Additionally, a systematic review of 11 studies did not identify a change in mortality associated with antimicrobial stewardship using audit and feedback in ICUs indicating that stewardship interventions that decrease antimicrobial use can be safely implemented in these challenging environments (9).
Data regarding the impact of stewardship interventions are commonly generated from quasi-experimental studies, often with relatively short follow-up periods. Long-term impact of stewardship interventions, particularly in the ICU settings, is not well described. A recent multicenter cohort across four ICUs in Toronto, Canada, evaluated the 3-year impact of audit and feedback and found sustained improvements in antimicrobial consumption and cost (10). In this issue of Critical Care Medicine, Sehgal et al (11) present a nearly 10-year follow-up on the long-term uptake of their antimicrobial stewardship audit-and-feedback program across ICUs at an urban academic medical center. Over the study period, the stewardship team made recommendations to alter antibiotic therapy in over 2800 cases with a sustained and stable moderate acceptance rate of 67%. The volume of antimicrobial reviews increased over time, as did the size of the stewardship team. Importantly, the study team evaluated predictors of antimicrobial stewardship intervention and also acceptance of stewardship intervention. The majority of interventions were focused on limiting unnecessary antibiotic use with recommendations to “discontinue” or “narrow” comprising 76% of the interventions, which is consistent with other reports (4). This is likely where stewardship has the greatest impact on antibiotic utilization, frequency of C. difficile and multidrug-resistant organisms, and antibiotic-associated toxicities. Although only a small proportion of the interventions were to “broaden coverage,” the potential to improve patient-level outcomes (e.g., mortality and length of stay) by ensuring adequate antimicrobial coverage could be clinically significant, though difficult to capture and to attribute to the role of stewardship. In this study, only the frequency of total intervention was quantified over time with predictors of intervention and intervention acceptance evaluated. It would be interesting to see the trend in the type of intervention over this long study period; as resistance rates and available antibiotics have changed over time, one would expect interventions to “broaden coverage” to increase.
Based on limitations of data available in their Stewardship Program Integrating Resource Information Technology (SPIRIT) stewardship database, there was a lack of adjustment for the presence of infectious diseases consults (IDCs) in the ICU. The stewardship team only intervened on patients not being followed by IDC. IDCs serve as an important extension of stewardship, particularly in ICU settings where the consult team has the bedside correlation to the patient’s case that may be lacking from a stewardship review, which is typically done from chart review (8,12). Stewardship teams and IDCs should work in conjunction with complex cases and ICU patients where intervention acceptance rates are lower. The data generated from their internal database could be used to advocate for practice changes such as recommending IDCs in burn-unit patients where infection management is often complex and their rates of intervention acceptance were low.
Effective antimicrobial stewardship is a long-term investment and programs must keep their foot on the gas. At our institution, a formal antimicrobial stewardship program had been established for nearly 7 years before being temporarily halted. During the period without stewardship, antimicrobial utilization and antimicrobial expenditures increased significantly (13). Since that time, our stewardship program has been reintroduced and completed over 20,000 antimicrobial reviews. Routine evaluation of this data has allowed us to identify areas of increased need for stewardship efforts and to adjust our strategies over time. Ongoing programmatic quality improvement to determine stewardship activities that have the most impact is essential. The data generated by the stewardship program’s SPIRIT database should be driving programmatic change and constant quality improvement for their stewardship program and can serve as a blueprint for other programs on the ways to evaluate their own stewardship programs. Identifying areas of highest stewardship impact and barriers to acceptance of stewardship interventions, and improving efficiency in stewardship reviews can provide opportunity to incorporate new stewardship targets or activities over time.
Personnel in stewardship face a unique cultural challenge related to their efforts to change prescribing behavior of peer clinicians. Resistance to stewardship interventions, particularly in ICUs where tensions can be particularly high, is significant emotional labor for stewardship teams. The audit and feedback strategy used by the stewardship program in this study is labor-intensive and requires consistent time and effort by stewardship personnel with infectious diseases knowledge and expertise. Additionally, this strategy can be seen as a “big brother” approach that does not necessarily equip frontline clinicians with the tools to optimize their own antibiotic decision-making (14). A culture change in stewardship is desperately needed where the term “antibiotic police” is forever abolished, and stewardship teams serve as an extension of the primary team working jointly to optimize patient care. A recent workshop report by the American Thoracic Society urges stewardship to be a core competency of critical care practitioners, thereby integrating stewardship into the ICU culture (15). There has been increased interest in the role of behavioral theory in stewardship practice and working to understand the drivers of unnecessary antimicrobial use in the ICU setting. Hardwiring long-term practice changes requires an understanding of the sociobehavioral and cultural factors, driving antimicrobial prescribing habits in the ICU. Without urgent improvements in the relationship between the stewardship teams and ICU teams, long-term successes in stewardship such as the ones seen by Sehgal et al (11) are likely to be the rarity and not the norm.
Widespread antimicrobial use and increasing antimicrobial resistance in ICUs illuminate the urgent need to improve ICU-based antimicrobial stewardship. The work of Sehgal et al (11) demonstrates that a sustained, positive impact on antimicrobial use in ICUs can be attained when stewardship programs are appropriately staffed and promoted. Expanding such programs should be a shared priority for infectious diseases and critical care clinicians alike.
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