Articles on antibiotic misuse have been popping up all over the place recently. Half of all hospital inpatients receive at least one antibiotic (Magill 2014). Antibiotic misuse, of course, contributes to the development of antibiotic resistance and predisposes to opportunistic infections such as fungal infections and those with C. difficile. In addition, antimicrobials are frequently related to adverse drug events.
Antibiotic stewardship programs have evolved to deal with the problem of increasing antibiotic resistance and have also been shown to reduce C. difficile infections, reduce adverse events related to antibiotics, and achieve considerable cost savings. CDC now recommends that all hospitals have antibiotic stewardship programs and there are also Joint Commission standards dealing with antibiotic stewardship.
Excellent resources on antibiotic stewardship are available for free from The Joint Commission, the CDC, and Johns Hopkins Hospital. The CDC core elements document has a nice checklist for you to see if your organization is meeting the core elements of a good antibiotic stewardship program.
Probably the three most widely used strategies for antibiotic stewardship are prior authorization, antibiotic “timeouts” and audit with feedback. Prior authorization means that the antibiotic must be approved by a designated individual, such as an Infectious Disease consultant, before it will be administered. Years ago many hospitals implemented prior authorization for expensive antibiotics so it was really a cost-saving strategy. Now it has become more important as a strategy to reduce unnecessary use of certain drugs as a quality and patient safety issue. While cost savings may no longer be the primary motivation for such programs it remains important to emphasize to hospital administration that there is a positive ROI (return on investment) for antibiotic stewardship programs that justifies provision of adequate resources for such programs.
Antibiotic “timeouts” are used to force a reassessment of antibiotic treatment. They are usually done 48 hours after the initial prescription of antibiotics, a time at which culture and sensitivities should be available to guide further therapy. Often antibiotics are begun empirically for a suspected bacterial infection so it’s always necessary to ask whether such an infection treatable with antibiotics is confirmed and whether any antibiotic or the specific antibiotic, dose, and route are still appropriate.
While almost all guidelines recommend audit and feedback to ordering physicians, such activities done after the fact don’t have nearly the impact that real time interventions do. Nevertheless, it’s very useful to have such reports available at departmental meetings so that constructive discussion and peer pressure can help change behavior when there are “outlier” antibiotic prescribers. (See also below regarding retrospective audit and feedback in the outpatient setting.) But even prospective audit and feedback may be problematic (Mehta 2014). One hospital had a successful antibiotic stewardship program for several years that was based on prior authorization of several antibiotics by Infectious Disease personnel or clinical pharmacists trained in infectious diseases. In mid-2009 they decided to take several antibiotics off the prior authorization requirement and instead did daily audit and feedback for these. The researchers found that use of the latter antibiotics increased after the change, while use of those that still required prior authorization did not change. Overall use of antibiotics also increased after the change. In addition, total hospital length of stay and length of stay after the first dose of antibiotic both increased after the change was made.
We recommend that a clinical pharmacist round with the multidisciplinary team daily. In preparation for rounds the pharmacist can check to see which patients are receiving antibiotics and check the microbiology reports to see if cultures and sensitivities are done. As each patient is discussed, at least 5 questions should be asked if the patient is on antibiotics:
1) Is there an indication for antibiotics? A continued indication?
2) Is the organism grown in the lab sensitive to the antibiotic(s)?
3) Is the antibiotic dose appropriate? (some may need to be adjusted for patient weight, renal function, drug interactions, etc.)
4) Is the route of administration appropriate? (eg. can the patient now be switched to an antibiotic via the oral rather than parenteral route?)
5) Should the antibiotic be discontinued? (what is the recommended duration of therapy?)
One common error is continuation of antibiotics that were meant for prophylaxis. The quality and pay-for-performance metric that requires cessation of surgical prophylactic antibiotics by 24 hours (for most surgeries) probably has had a beneficial effect on reducing inappropriate antibiotic therapy.
Some useful tools may be protocol-based and either written or computerized. One useful tool is the automatic stop order. These should be part of protocols approved by the medical staff and mandate that the antibiotic be discontinued after a specified time interval. The physician would have to reorder the antibiotic if he/she feels further treatment is indicated. Similarly, your medical staff may approve automatic switch protocols in which a switch from parenteral to oral antibiotics may take place once certain criteria are met. Keep in mind that standardized order sets for various conditions may be very important in ensuring correct use of antibiotics but these must be kept up to date so that you do not inadvertently encourage inappropriate use of antibiotics.
Note that we like computerized physician order entry (CPOE) to require an indication for any antibiotic ordered. This helps clarify whether an antibiotic is for prophylaxis or for treatment of an infection. It is also useful to know which type of infection the antibiotic is for (eg. UTI vs. lower respiratory infection, etc.), especially since a patient may have potentially more than one site of infection.
There should be a physician leader responsible for ensuring desirable outcomes of your antibiotic stewardship programs. The CDC core elements include that one individual be responsible for outcomes of antibiotic stewardship programs and note that those that have been most successful have a physician leader. Hospitals often have their head of Infectious Diseases in this role. However, not all hospitals have an ID physician on staff and sometimes another highly visible physician (eg. a hospitalist) may be more appropriate in this role. It’s important to ensure that this physician leader have adequate time (and remuneration, if necessary) to function in this role. The CDC core elements also recommend someone with drug expertise be a co-leader of the antibiotic stewardship program and recommend that a single pharmacy leader be charged with this responsibility. Note that the CDC recommends that the hospital’s Pharmacy and Therapeutics Committee not be the body responsible for operating the antibiotic stewardship program, though it obviously needs to be kept abreast of its activities.
Many organizations have a nurse leading many of their infection control programs. But we’ve also seen others function very well in this role. For example we have seen a laboratory director, with additional training in infection control, nicely integrate the microbiology and IT aspects of infection control with the pharmacy and clinical aspects. Either person can be very valuable in assembling the reports that are needed for your program and overseeing multiple aspects of the program but you will likely get more medical staff buy-in to the antibiotic stewardship program if there is a physician leader.
Having hospital leadership ensure adequate support for antibiotic stewardship programs is much easier when you can demonstrate that such have a positive ROI (return on investment) both in terms of savings on medications, savings from fewer complications and reduced lengths of stay, meeting pay-for-performance measures, and avoiding penalties for unnecessary readmissions. The Joint Commission antibiotic stewardship toolkit provides guidelines for you to develop the business case for antibiotic stewardship customized for your organization or facility.
Education is a key component of all antibiotic stewardship programs. While most educational efforts are aimed toward the medical staff, it is also important that all nursing and pharmacy staff have a thorough understanding of the needs and principles of antibiotic stewardship programs. Our own interactions with physicians regarding antibiotic use have led us to the conclusion that focusing on cost issues will get you nowhere. Similarly, while physicians understand the problem of antibiotic resistance, most do not think their antibiotic decisions in a single case have any substantial impact on overall resistance issues. Therefore, we recommend you focus more on issues like prevention of C. difficile infections and adverse drug reactions. Again, a recurring theme for us is “stories, not statistics”. You can much more easily get staff buy-in when you tell them real-life stories about individual cases and patients than you can by spewing off a host of statistics.
Other hospital staff also have important roles in promoting antibiotic stewardship. For example, your IT staff can help ensure that clinical decision support be available to those who prescribe antibiotics. This would also include easy access to antibiotic prescribing aids and charts with the most up-to-date microbiology antibiotic sensitivity patterns at the facility. IT staff may also work with clinicians to develop computer-generated alerts that might notify a clinician of a drug interaction or alert the clinician to other conditions. For instance, an order for an anti-diarrheal in a patient on antibiotics could prompt for testing for C. difficile. Clinical decision support tools can also alert to the need for dosage adjustment when, for example, renal function is deteriorating.
Antibiotic stewardship programs should be used in healthcare facilities of all types. The benefit of an antibiotic stewardship program in pediatric patients was recently demonstrated (Newland 2014). Those researchers found that no children whose physicians followed the recommendations of the antibiotic stewardship team were readmitted to the hospital (within 30 days) compared to a 3.5% readmission rate in those for whom the physicians did not follow the team’s recommendations. Moreover, length of stay was not longer in those in whom the recommendations were followed.
Antibiotic misuse, of course, is not just a hospital problem. Antibiotics are also often prescribed during outpatient visits. A recent study from China showed found that antibiotics were included in 52.9% of outpatient visit prescription records and, of these, only 39.4% were prescribed properly (Wang 2014). The numbers in China may be inflated because of a perverse incentive to sell antibiotics to help finance the outpatient sites. But we have little doubt that antibiotics are likely overprescribed in US outpatient settings as well.
An outpatient antibiotic stewardship program in a pediatric network (Gerber 2014), consisting of provider education and audit and feedback, reduced prescribing rates for broad-spectrum antibiotics for acute respiratory infections by about 50%. However, once the audit and feedback component was discontinued, prescription of the broad-spectrum antibiotics returned almost to baseline levels.
One very interesting recent study in the US showed that antibiotic prescriptions are more frequent during later hours of primary care sessions (Linder 2014). The researchers looked at antibiotic prescriptions for acute respiratory infections (ARI’s) in primary care clinics that held 4-hour sessions in either the morning or afternoon. They found that prescriptions for “antibiotics sometimes indicated” and “antibiotics never indicated” ARI’s increased throughout both the morning and afternoon sessions. The odds ratios increased with each hour of clinic (compared to the first hour the odds ratios were 1.01, 1.14, and 1.26 respectively for the second, third and fourth hours of clinic.
We are not surprised by the above results. This sort of “fatigue” that may affect decision making is probably quite common. We’ve previously discussed that colonoscopies done later in a session are less likely to be complete and less likely to discover adenomas (see our May 3, 2011 Patient Safety Tip of the Week “It’s All in the Timing”).
Dr. Michael Bell (Bell 2014), commenting on the Chinese study by Wang et al., also mentioned that easy access to antibiotics, including over-the-counter availability of antibiotics, is a problem in global misuse of drugs. We were surprised to hear that antibiotics were available over-the-counter so we did an internet search and found at least one site (InternetDrugNews.com) that described how antibiotics can be obtained without a prescription. They sent investigators, some undercover, to try to obtain antibiotics without a prescription. It turns out your local pet store(!) probably sells many antibiotics intended for fish and these don’t require a prescription. The article also describes how antibiotics may be obtained on the internet and from various other sources without prescriptions. The article goes on to describe why some people would try to get antibiotics these ways and describes the reasons why such practices may be dangerous.
And, of course, we have the old adage “you can’t improve anything that you can’t measure”. So what metrics should you be following? Obviously you want to monitor total antibiotic prescribing in some fashion (DOT, or days of therapy, is a popular measure) but you also want to track trends in antibiotic resistance, trends in length of stay (LOS), adverse drug reactions related to antibiotics, incidence of C. difficile infections, etc. And your CFO will want to see some measures of cost savings (compare to the business case you made for the antibiotic stewardship program).
Antibiotic stewardship program make a lot of sense from both a patient safety and financial perspective. Is your organization using such programs to their fullest capabilities?
Magill SS, Edwards JR, Beldavs ZG, et al. Prevalence of Antimicrobial Use in US Acute Care Hospitals, May-September 2011. JAMA 2014; 312(14): 1438-1446
The Joint Commission. Antimicrobial Stewardship Toolkit.
CDC. Core Elements of Hospital Antibiotic Stewardship Programs.
Johns Hopkins Medicine. JHH Antibiotic Management Guidelines (updated annually).
Mehta JM, Haynes K, Wileyto EP, et al. Comparison of Prior Authorization and Prospective Audit With Feedback for Antimicrobial Stewardship. Infect Control Hosp Epidemiol 2014; 35(9): 1092-1099
Newland JG, Hersh AL, Gerber FS, et al. "Impact of a pediatric antimicrobial stewardship program on length of stay and readmissions" IDWeek 2014; Abstract 1217 as reported by Susman E. Antibiotics Control Cuts Kids' Hospital Readmission. MedPage Today. Oct 9, 2014 | Updated: Oct 10, 2014
Wang J, Wang P, Wang X, et al. Use and Prescription of Antibiotics in Primary Health Care Settings in China. JAMA Intern Med 2014; online first October 6, 2014
Gerber JS, Prasad PA, Fiks AG, et al. Durability of Benefits of an Outpatient Antimicrobial Stewardship Intervention After Discontinuation of Audit and Feedback. JAMA 2014; Published online October 10, 2014
Linder JA, Doctor JN, Friedberg MW, et al. Time of Day and the Decision to Prescribe Antibiotics. JAMA Intern Med 2014; online first October 6, 2014
Bell M. Antibiotic Misuse. A Global Crisis. JAMA Intern Med 2014; online first October 6, 2014
InternetDrugNews.com. Antibiotics Without A Prescription? InternetDrugNews.com
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