By Kelly M. Pyrek
It has been more than a decade since several medical societies outlined recommendations to optimize the use of antimicrobials through antibiotic/antimicrobial stewardship programs (ASPs) in acute-care institutions. As Dodds, et al. (2017) explain, "Antimicrobial stewardship refers to programs and interventions designed to improve antimicrobial prescribing—the right drug, dose, duration, and route of administration—to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use such as toxicity, selection of pathogenic organisms, and emergence of resistance."
In 2007, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) provided guidance to promote the judicious use of antimicrobials and preserve their usefulness in the setting of growing resistance, and in 2014, the Centers for Disease Control and Prevention (CDC) issued its Core Elements of Hospital Antibiotic Stewardship Programs, in which provisions for leadership commitment, accountability, drug expertise, action steps, tracking/monitoring antibiotic prescribing and resistance patterns, reporting and educating clinicians about resistance and optimal prescribing, were explored. But the ASP implementation and management of the ASP process has not been without its challenges. As Dodds, et al. (2017) observe, "In 2011, the IDSA Emerging Infections Network surveyed its membership to determine characteristics of ASPs and reported that clinicians and administrators differ in their assessments of outcomes of importance needed to support these programs. An overwhelming majority (83 percent) of administrators underscored the importance of evidence of cost savings, whereas 63 percent to 72 percent of physicians were more focused on patient outcomes, citing reductions in Clostridium difficile infection (CDI), adverse events, and resistance rates as the most important indicators to justify an ASP. In another survey, infectious disease physicians and pharmacists ranked appropriateness of antimicrobial use, infection-related mortality, and antimicrobial-associated length of stay (LOS) as the metrics of highest importance to demonstrate the impact of an ASP."
As hospitals work through the barriers and seize the opportunities related to ASPs, the role of the pharmacist has become a significant component of preserving the power of these therapies, including agents of last-resort to fight multidrug-resistant organisms in the acute-care setting. Championing the importance of clinical medicine and pharmacy in hospital stewardship efforts is Elizabeth S. Dodds Ashley, PharmD, MHS, BCPS, associate professor of medicine at Duke University School of Medicine, who says that, "Clinical pharmacy is very integrated and medical centers today value the role of pharmacists to guide antibiotic treatment as appropriately as possible."
Dodds Ashley explains that in addition to the traditional pharmacy role, hospital-based pharmacists possess an evolving array of skills that can directly impact and improve patient outcomes. "The expertise of the clinical pharmacist is rooted in helping to guide appropriate antimicrobial therapy, including the obvious tasks such as ensuring that the dose is correct, making sure there are no potential adverse drug interactions, but the role has also expanded to become more aggressive," she says. "So, instead of just accepting allergies for what they are, many clinical pharmacy practices now screen patients with a list of penicillin allergies to try to de-label them from penicillin allergy if appropriate, based on either clinical signs and symptoms from a reaction the patient had, or in some places where pharmacists have collaborative practice acts, they can actually perform penicillin skin testing under protocol supervised by physicians."
Dodds Ashley continues, "Pharmacists sit at a unique vantage point in the hospital and because of that, they are able to see the entire medications picture in the institution, as well as the individual scenarios at the patient level, or at the unit level. Because of the numerous hand-offs in patient care, clinicians don't see the big picture, but the pharmacists do, and that helps with stewardship efforts. Pharmacists notice the trends, whether a facility is using more of a certain drug, or whether there has been an increase in cases requiring more carbapenems in the ICU, for example, and they can say, 'Let's investigate this.' With their drug expertise and that unique vantage point in the facility, pharmacists are perfectly situated to see the global antibiotic use in the institution as well as guide specific medication regimens to ensure that they are optimal."
According to the CDC, pharmacy-driven interventions within ASPs include the following:
- Automatic changes from intravenous to oral antibiotic therapy in appropriate situations and for antibiotics with good absorption (e.g., fluoroquinolones, trimethoprim-sulfamethoxazole, linezolid, etc., which improves patient safety by reducing the need for intravenous access)
- Dose adjustments in cases of organ dysfunction (e.g. renal adjustment)
- Dose optimization including dose adjustments based on therapeutic drug monitoring, optimizing therapy for highly drug-resistant bacteria, achieving central nervous system penetration, extended-infusion administration of beta-lactams, etc.
- Automatic alerts in situations where therapy might be unnecessarily duplicative including simultaneous use of multiple agents with overlapping spectra e.g. anaerobic activity, atypical activity, Gram-negative activity and resistant Gram-positive activity
- Time-sensitive automatic stop orders for specified antibiotic prescriptions, especially antibiotics administered for surgical prophylaxis.
- Detection and prevention of antibiotic-related drug-drug interactions (e.g., interactions between some orally administered fluoroquinolones and certain vitamins)
The CDC's Core Elements document makes it clear that in addition to the physician who will be responsible for outcomes within the institution's ASP, facilities must identify a single pharmacy leader who will co-lead the program. "I think the CDC has done a nice job of elevating the role of the pharmacist by singling them out as necessary co-leaders of antimicrobial stewardship programs," says Dodds Ashley. "The Core Elements guidance clearly gives us a seat at the table and I think it's tremendous that it is well recognized that pharmacy is a key element to ASPs."
Another critical stakeholder at that table is the infection preventionist. As the CDC's Core Elements note, " Infection preventionists and hospital epidemiologists coordinate facility-wide monitoring and prevention of healthcare-associated infections and can readily bring their skills to auditing, analyzing and reporting data. They can also assist with monitoring and reporting of resistance and CDI trends, educating staff on the importance of appropriate antibiotic use, and implementing strategies to optimize the use of antibiotics."
"There are so many opportunities for IPs, healthcare epidemiologists and pharmacists to collaborate," says Dodds Ashley. "There are also many ways that IPs can get assistance from the pharmacy and the ASP team, especially when there is a constant need for data. For example, in outbreak investigations, IPs are looking for past antibiotic exposures on a unit in which there has been an outbreak. The stewardship team has probably already worked out a way to track antibiotic use and so for the IP, this is a great resource. Beyond that, we are much more powerful in our interventions when we work in a united fashion. Recently in one of the hospitals in which I work, there was an SSI outbreak and during the investigation, the facility's stewardship team and the pharmacy were brought in and so all their knowledge and resources were applied. For example, there can be quick changes to guidelines and order sets that are often driven more to the stewardship team to get patients on more appropriate surgical prophylaxis that covers more pathogens. At the same time, some power was applied to some infection prevention recommendations relating to how pharmacy products should be prepared. The stewardship team brought the pharmacy resources to bear and was able to change the way products were prepared at the facility. Pharmacy and the ASP team can be a tremendous resource and I think we constantly need to look for ways that we can team together. Sometimes pharmacy, from the stewardship perspective, reviews C. diff cases to see if antibiotics are still necessary, which is clearly within their expertise. What we have realized is that instead of sending an IP to see if isolation signs are up, the pharmacist can just add that to their checklist and save the IP some work. There are numerous opportunities for shared work that expands a facility's resources without spending a dime and increases productivity. There are also plenty of opportunities for collaboration, whether it is sharing data or brainstorming about best practices. Sometimes there may be an intervention that doesn't seem possible either from the IP or the stewardship side, but together, you can creatively figure out the resources to get it done."
Collaboration is essential in smaller community hospitals, where budgets may be tight and resourcing is limited. "I work for Duke's Antimicrobial Stewardship Outreach Network and we are contracted by community hospitals to help with their stewardship efforts. So, I am in small community hospitals every day and a collaborative approach is critical in this kind of setting. There are many institutions that have found extremely creative ways to get antimicrobial stewardship work done in a very resource-limited setting. I have seen many hospitals band together and formally or informally pool resources, which is the really smart way to get this done."
It is also critical that hospital leadership support ASPs. As the CDC's Core Elements note, " Leadership support is critical to the success of antibiotic stewardship programs." This support can include:
- Formal statements that the facility supports efforts to improve and monitor antibiotic use.
- Including stewardship-related duties in job descriptions and annual performance reviews,
- Ensuring staff from relevant departments are given sufficient time to contribute to stewardship activities
- Supporting training and education
- Ensuring participation from the many groups that can support stewardship activities.
- Financial support greatly augments the capacity and impact of a stewardship program and stewardship programs will often pay for themselves, both through savings in both antibiotic expenditures and indirect costs.
"With so many mandates and priorities for frontline providers, it's important to drive awareness to the C-suite of the criticality of ASPs," says Dodds Ashley. " We have made great strides lately but it still needs to become an important issue to patients and families as well. This needs to be something that everyone is working toward."
In terms of the challenges ahead, Dodds Ashley identifies access to quality data as one of the key barriers to ASP success. "There have been great strides made in the basics of antibiotic use data, but requires work that doesn't always get prioritized in hospitals but is essential to success. So, having a mechanism to get that higher on the list of institutional priorities -- and it's getting there -- would help tremendously. Another barrier is the multi-tasking that is often required of the pharmacy leader. "When I go to community hospitals I meet the people who have been delegated as the stewardship pharmacist and frequently it's the same person who is the AS pharmacist and the cardiology pharmacist and the oncology pharmacist, and so getting people with truly dedicated time to focus on good data is a real challenge."
Despite these barriers, Dodds Ashley says she remains hopeful about the future of ASPs. At every scientific congress these days there are more people presenting new and novel metrics relating to ASPs. Have we found THE one yet? We haven't. Are we working hard on it? We are, and there are grants to fund research like never before. There are many smart scientists working on this problem right now. It's an exciting time but the work isn't finished yet, there is still a lot to do."
Dodds Ashley points to the ongoing emerging and present pathogenic threats which make stewardship an imperative: "Stewardship is critical to addressing resistance issues. Despite efforts to greatly expand the pipeline of therapeutic agents, we still are left with suboptimal treatments that don't meet the needs of all our patients. The reality is that this is a unique class of medications and it is one of the only medication classes that you can give to one patient and affect subsequent patients with that decision to administer. If I give you a beta blocker for your blood pressure, for example, that beta blocker won't influence whether it will work for your grandchildren. But antibiotics do. We do not have a limitless pipeline of anti-infective agents and there's a whole host of reasons behind that, but we must preserve what we have still available for use."
By now it is a well-known fact among clinicians that approximately half of patients admitted to hospitals will receive antibiotics. According to a report from the Pew Charitable Trusts, "National antibiotic use patterns illustrate the potential for individual hospitals to curb prescribing of these drugs, an essential step in slowing the spread of resistance and avoiding adverse events. An analysis from the CDC has uncovered worrisome trends in hospital prescribing; stewardship efforts should focus on reversing these trends." A CDC analysis of inpatient antibiotic prescribing data from the Truven Health Analytics’ MarketScan Hospital Drug Database concluded that between 2006 and 2012, overall antibiotic use remained static; however, the prescribing of certain classes of antibiotics changed as follows:
- Use of broad-spectrum antibiotics increased significantly. Broad-spectrum antibiotics are agents that target a wide array of bacterial pathogens. They include glycopeptides, beta-lactams and beta-lactamase inhibitor combinations, carbapenems, macrolides, and third- and fourth-generation cephalosporins.
- Use of narrow-spectrum antibiotics decreased. Narrow-spectrum antibiotics are medications effective in treating a limited and targeted group of pathogens. They include penicillins, aminoglycosides, and first- and second-generation cephalosporins.
As the Pew Charitable Trusts report says, "Although these estimates measure only the volume, and not the appropriateness, of prescribing, the trend toward using broad-spectrum agents is cause for concern, because these types of antibiotics have been shown to significantly increase the risk of drug-resistant infections. Another worrisome trend is that fluoroquinolones were the most commonly prescribed class of antibiotics in hospitals, accounting for more than 16 percent of all antibiotic use. These broad-spectrum antibiotics have significant toxicities that have been associated with serious and sometimes permanent side effects affecting tendons, muscles, joints, nerves, and the central nervous system. Because of these toxicities, the Food and Drug Administration recently issued an advisory recommending that fluoroquinolone use be avoided for patients with uncomplicated bacterial infections, such as urinary tract infections and sinusitis, and that these patients be given alternative treatment options. Reducing unnecessary or inappropriate use of fluoroquinolones will help minimize the risks associated with them." The report adds, "New information on prescribing patterns can support hospital antibiotic stewardship programs, which are designed to optimize antibiotic use, by identifying areas to target stewardship interventions to reduce any inappropriate use. Further research is necessary to evaluate the appropriateness of how these drugs are used in U.S. hospitals, but the high volume of fluoroquinolone use and the increasing use of other broad-spectrum antibiotics present potential targets for antibiotic stewardship efforts."
Centers for Disease Control and Prevention (CDC). Core Elements of Hospital Antibiotic Stewardship Programs. Accessible at: https://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html
Dodds-Ashley ES, Kaye KS, DePestel DD and Hermsen ED. Antimicrobial Stewardship: Philosophy Versus Practice. Clinical Infectious Diseases. Vol. 59, No. 3. Pages S112-S121. October 2014.
The Pew Charitable Trusts. Research & Analysis: Antibiotic Prescribing Trends in U.S. Hospitals Raise Flags. Feb. 24, 2017. Accessible at: http://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2017/02/antibiotic-prescribing-trends-in-us-hospitals-raise-flags
The Pew Charitable Trusts. Trends in U.S. 2017. Antibiotic Use. Accessible at: http://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2017/03/trends-in-us-antibiotic-use
The Pew Charitable Trusts. Antibiotic Stewardship Programs Vary in U.S. Hospitals. 2016. Accessible at: http://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2016/10/antibiotic-stewardship-programs-vary-in-us-hospitals