The Effectiveness of Stewardship Strategies

THE EFFECTIVENESS OF STEWARDSHIP STRATEGIES

How effective a particular action is will be determined by the parameter used to measure it. In the case of stewardship programmes almost all of the individual components of the two IDSA/SHEA strategies can be shown to reduce resistance development, adverse effects or costs, but there are few actions that result in favourable changes in all three criteria.

Both of the core strategies of prospective audit and formulary restriction are active measures and, as such, are more effective than passive ones. Prospective audit/ intervention has been shown to reduce inappropriate use of antibiotics, achieve cost savings and, in some cases, restricted the isolation of particular antibiotic-resistant organisms. Formulary restriction/preauthorization has similarly been shown to reduce antibiotic consumption, and this may be immediate and significant, but its long-term impact on restricting resistance development is not proven. Education of patients to dissuade them from pressurizing prescribers for antibiotics particularly for colds and flu or other viral infections is now well established, but education of prescribers (conference presentations, teaching sessions, e-mail alerts and bulletins) is a passive approach which, by itself, has been shown to have only a marginal and short-term impact. Clinical path-ways (also known as critical care pathways or care maps) are intended to reduce the variability both in the quality of care and in-patient outcomes by the adoption of defined, standardized and sequenced procedures for patients with specific conditions in this context, infections. The use of a clinical pathway that includes a specified antibiotic regimen in the treatment of community-acquired pneumonia, for example, has been shown to be capable of reducing the duration of hospital stay and duration of antibiotic therapy, and there is strong evidence that practice guidelines and clinical path-ways incorporating local resistance patterns can generally improve antimicrobial utilization.

Four other elements of the IDSA/SHEA that have been shown to afford clear benefits are the use of antimicrobial order forms, de-escalation of therapy, parenteral to oral conversion and optimized dosing. Order forms are particularly useful when antibiotics are prescribed for prophylactic purposes to reduce the incidence of infection following surgery. In this situation there is a tendency to continue the course of treatment for an unnecessarily long period after the operation, and studies have shown that order forms with a default stop date have diminished drug consumption with no adverse effect. When hospital treatment for an infection begins, it is often the case that the organism responsible has not been identified, so initial treatment is empirical or ‘blind ’ and, in order to maximize the probability of inhibiting the pathogen, it may involve the use of either a broad-spectrum antibiotic, or of two or more different drugs. Once the organism has been identified it is good practice to replace broad-spectrum antibiotics (or redundant components of a combination) with a drug having more specific activity, because the continued unnecessary use of broad-spectrum therapy contributes to selection of resistant pathogens. Converting from intravenous to oral therapy affords a benefit primarily in terms of cost reduction but may also permit earlier removal of intravenous lines which facilitate the establishment of infections by skin pathogens like Staph. epidermidis. Oral antibiotics are usually cheaper than intravenous ones, quite simply because the use of the latter is largely restricted to hospitals anyway, so their manufacturers have to recover the development costs from lower lifetime sales. Optimized dosing is, as the name implies, modifying the antibiotic dose to suit an individual patient’ s circumstances. Factors that may influence the dose, and hence the effectiveness of the therapy, include the patient’s physical characteristics (weight, age, immune status, renal function), the site of infection and the pharmacokinetics of the drug which determine its access to, and concentration at, that infection site.

Two procedures that have been advocated as means of restricting resistance development are cycling of antibiotics and routinely using them in combination, particularly for infections with a long time-course of treatment. However, there is little evidence to support the use of routine cycling —the planned replacement of one specific antibiotic, or category of antibiotics, with another at predetermined intervals—as a means of controlling resistance. True cycling involves the return into use of the original antibiotic after a specified time, and although the first switch may lead to a reduced incidence of resistance to the first drug, some studies have shown that when it is subsequently reintroduced the original resistance level is quickly restored. Using antibiotics in combination as a means of restricting resistance development is well established and of undoubted benefit in the treatment of both tuberculosis, for which the duration of therapy is typically 6 months, and in HIV/AIDS which requires life-long treatment. During such long time periods the number of pathogen replication cycles is so large, and in hese two examples the mutation frequency is so high, that the probability of a resistant mutant arising and being selected as the predominant strain at the site of infection is significant, so using two or more agents with different modes of action is both logical and effective. However, the same logic has been applied to other, relatively short-term, infections without clear evidence of benefit.