The goals of formal antimicrobial stewardship programs are to achieve optimal clinical outcomes related to antimicrobial use, minimize toxicities and other adverse events, reduce the cost of health care for infections, and limit the selection of antimicrobial resistance. The CDC has provided guidance regarding the essential components of a stewardship program. Each program should have a physician leader, preferably with training in infectious diseases and specifically antimicrobial stewardship, who is responsible for program outcomes. Each program must also identify a pharmacist leader, who is responsible for working to improve antimicrobial use. To be effective, programs must have support within administration and should work closely with hospital programs with clear overlapping goals such as the infection control program, whose goals include reduction of C. difficile infections. Other key stakeholders include the Microbiology Laboratory, the Quality Improvement Department and other front-line clinicians. ASP interventions are designed to measure and optimize antimicrobial use and minimize adverse events and resistance. The best strategies for the prevention and containment of antibiotic resistance is not definitively established due to a lack of clinical evidence. Most stewardship programs use multiple interventions simultaneously and are often in collaboration with key stakeholders such as infection control programs to minimize the spread of resistance. Programs should select interventions based on local antibiotic utilization patterns, available resources, and expertise. Effective ASP programs can be financially self-supporting and improve patient care. In the literature, these programs have shown decreased antibiotic use by up to 36 percent and annual savings up to $900,000. The emphasis of this module, again, will be on ASP interventions in the inpatient setting. Antibiotic oversight is the foundation of any stewardship program, and should include one or both of the following strategies, preauthorization or prospective audit and feedback. Preauthorization requires clinician to obtain approval for select antimicrobials before they are prescribed. Prospective audit and feedback involves trained staff, usually ID pharmacists and/or physicians who review antimicrobial orders after they are placed and provide verbal or written recommendations to the primary team. Both methods have shown decreased antibiotic use and reduced antibiotic resistance without negatively impacting patient care. First, looking at the advantages, preauthorization reduces initiation of unnecessary and inappropriate antimicrobials. It optimizes empiric choices and influences downstream use. It decreases antibiotic cost and can focus on those that are extremely high costs in certain institutions. Prospective audit and feedback on the other hand, provides educational benefit to clinicians, does not interfere or delay first doses of antibiotics, allows for provider autonomy and empiric choices, and allows ASP members to address de-escalation and duration of therapy once there is more clinical data available. Logistically for ASP programs, it also allows flexibility and timing and frequency of recommendations. Now, let's compare the disadvantages between these strategies. Preauthorization occurs in real time and is resource intensive, often requiring extensive coverage through an approval pager. It focuses on empiric use rather than downstream use. Because first doses are not generally released without approval, there may be a perceived loss of prescriber autonomy and this may inadvertently delay first doses. Prospective audit and feedback is typically labor-intensive due to more intense case reviews once more data is available. Often, identifying appropriate patients for intervention may itself require tailored computerized system builds which are also time-intensive to build and validate. Other supplemental strategies include development of facility-specific clinical protocols, point of care interventions such as automatic IV to PO conversions, dose optimization, and therapeutic drug monitoring. Prescriber lead review of antimicrobials such as the antimicrobial timeout. Antimicrobial allergy assessment for example, delabeling of penicillin allergies. Education of clinicians and patients and other interventions that contribute to the reduction of C. difficile infections. Implementation of facility-specific clinical practice guidelines can lead to substantial changes in antibiotic use for infections commonly treated in hospitals. Most published studies of clinical practice guidelines have involves pneumonia, including community-acquired pneumonia, CAP and hospital-acquired pneumonia in adults. Specific improvements in antibiotic use associated with implementation of facility-specific guidelines have included statistically significant increases in likelihood of adequate initial therapy, use of narrower spectrum antibiotic regimens, earlier switched from IV to PO therapy, and shorter duration of treatment. For those studies powered to detect differences in clinical outcomes, reductions in mortality, length of stay, adverse events, recurrence or readmission, and treatment costs have been demonstrated. Hospitalized patients receiving antimicrobial therapy are generally started on intravenous antibiotics. There are some antibiotics that have an extremely high bioavailability and can be converted to oral therapy once the patient meets certain criteria. Antibiotics with high bioavailability include fluoroquinolones, linezolid, metronidazole, clindamycin, and trimethoprim-sulfamethoxazole. Antifungals with high bioavailability include fluconazole and voriconazole. Studies have shown that early conversions from IV to PO antibiotics can result in reduced length of hospital stay, reduced health care costs, reduced infections and reduced morbidity. Programs can assist in creating guidelines and protocols for renal dosing, dialysis dosing, alternative dosing strategies of beta-lactams, and therapeutic drug monitoring. Example programs include vancomycin and aminoglycosides per pharmacy, which have been shown to reduce nephrotoxicity, improved time to therapeutic levels, and in some studies, improve clinical outcomes. Strategies to decentralize routine antibiotic review include self-stewardship, antibiotic timeouts with or without automatic stop orders and prompting on checklists. Successful programs appear to require a methodology that includes persuasive or enforced prompting. Antibiotics stop orders for example, have been best studied with vancomycin. One study reporting significantly decreased continuation 11 percent versus 25 percent before and after implementation of a three-day vancomycin stop order in situations without documented gram-positive infections. Strategies include educational meetings with didactic lectures and distribution of educational pamphlets and materials. Educational outreach should be done regularly to both refresh and update the learners regarding principles of antibiotic use and to reach new prescribers. Training programs should integrate antimicrobial stewardship program education in their core curriculum. Education alone however, is a week intervention and is best used in conjunction with other ASP interventions for sustained effects. Institutions may also target high risk patients with invasive fungal infections. In designing interventions, programs should consider local, fungal epidemiology and antifungal resistance rates. Some potential targets for programs include de-escalation of empiric anti-candidal coverage to fluconazole as was discussed in the Candidemia module. Programs can also assist in the optimization of antifungal dosing by therapeutic drug monitoring or TDM. Serum drug monitoring may be considered to monitor for efficacy and/or toxicity. But it should be noted that recommendations are often based on limited data of associations between blood levels and response or toxicity, not prospectively controlled trials. TDM may be helpful in patients failing therapy, treatment of uncommon or in vitro less susceptible organisms, extensive or deep-seated disseminated disease, patients with questionable absorption or drug interactions and can be used to monitor for adherence.
