Discussion Of Results And Implications For Practice

Given the broad array of targeted behaviors, the variation in interventions (even within categories) and the differences in the clinical settings, it is difficult to generalize the results from these individual studies and arrive at broadly applicable recommendations for improving antibiotic prescribing in any community. However, several general observations may be cautiously made.

The simple, single intervention studies (mailed or published educational materials, audit and feedback) generally resulted in no or little change in prescribing behavior. Previous systematic reviews have concluded that passive methods of physician education such as traditional conferences and lectures as well as publication of guidelines have very limited impact (O'Brein et al., 2003a-d; Oxman et al., 1995). The most plausible explanation for this is that these interventions often fail to address the root causes of inappropriate prescribing. Simply drawing the physician's attention to the behavior (audit and feedback) or recommending an alternate behavior (educational materials) may not provide the physician with the tools to change a behavior that likely is quite ingrained and multifactorial in its origins. It bears mentioning that these low cost interventions may result in cost savings to governments and other insurers even if the results are marginal given the high cost of prescription medications. Small changes in prescribing are unlikely, however, to reduce the incidence of antibiotic resistant bacteria in a community.

The one exception to this lack of effect of simple interventions was the impressive change in macrolide use in Finland following publication of a guideline recommending against the use of this class of antibiotics for Group A streptococcal infection. This result is unexpected given the limited effect of published guidelines on physician behavior. The basis of the recommendation was patient safety as there were concerns regarding treatment failures due to the increasing rate of macrolide resistance. This emphasis on patient safety may account for the impressive impact of the written recommendations compared with other reports of this intervention. However, as time-series analysis demonstrated, the effect of this single intervention (occurring at one point in time, i.e., single publication) appeared to wane somewhat over time as indicated by the positive slope of the post-intervention prescribing rates. Thus, over the long term, the effect of this recommendation may wane as memory of the publication fades.

The more complex the intervention, the more likely it was to produce important changes in antibiotic prescribing behavior. Educational meetings produced modest improvements in prescribing. The study examining patient education materials alone or in combination with another intervention demonstrated the benefit of including patient-based education in the intervention (Mainous et al., 2000). This observation provided the rationale and impetus for the community-based, multifaceted interventions undertaken by the CDC and other groups of researchers. Combinations of interventions in most instances, produced moderately large reductions in antibiotic use which was sustained in those studies with follow-up data, depending on the specific intervention and targeted behavior (Belongia et al., 2001; Finkelstein et al., 2001; Flottorp et al., 2002; Gonzales et al, 1999; Hennessy et al, 2002; Perz et al, 2002; Stewart et al., 2000). One notable exception was the Norwegian study (Flottorp et al., 2002) where researchers designed the intervention to specifically address previously identified barriers to change. There was no change in antibiotic use for sore throat in this study, despite the tailored interventions possibly due to the passive nature of the interventions or an inadequate duration of follow-up. This strengthens the impression that one cannot derive broad-based recommendations from these studies to apply to any clinical situation in any community.

It appears that interventions aimed at increasing the prescribing of certain recommended first-line antibiotics for specific infections are more likely to produce substantial changes in prescribing than those interventions targeting overall inappropriate antibiotic use. As discussed in the introduction, the root causes of antibiotic misuse in the community outpatient setting are manifold and may include physicians' succumbing to pressure from patients, lack of understanding by the physician as to the necessity for antibiotics in certain clinical conditions, diagnostic uncertainty as to the true nature of the patient's illness, and constraints on the physician's time to explain the nature of the illness and the reasons an antibiotic is not indicated. Convincing a physician or patient that a particular antibiotic (usually the most narrow spectrum agent for the condition) should be his or her first choice should be relatively simple as long as appropriate justification for the recommendation is made. It stands to reason, however, that completely eliminating prescribing for a particular indication, such as a viral URI, in a clinical situation in which the physician would usually prescribe an unnecessary antibiotic would be a more difficult behavioral change. While this generally holds true for most of the reviewed studies, promoting the prescribing of firstline agents was not as straightforward a task as might be predicted. One potential explanation for this is that physicians may consider these prescribing recommendations a limitation to their clinical freedom. In addition, physicians want to prescribe what they think are the best medications for the individual patient which often means a broad-spectrum agent to protect against potentially resistant organisms regardless of the ecological consequences.

Several of the trials addressed patient-based outcomes such as changes in antibiotic resistance patterns as a result of altered antibiotic use (Belongia et al., 2001; Hennessy et al., 2002; Perz et al., 2002; Seppala et al., 1997) and illness outcomes following the withholding of antibiotics for certain conditions (Arroll et al., 2002; Little et al., 2001). Over the intervention periods (usually between 1 and 3 years) no substantial or persistent reductions in incidence of isolating resistant bacteria were observed in any of the studies except for the Finnish macrolide study (Seppala et al., 1997), where changes were observed in macrolide resistance rates after approximately 2 years. In contrast, no sustained reduction in penicillin resistance was observed with overall reductions in antibiotic use in several communities (Belongia et al., 2001; Hennessy et al., 2002; Perz et al., 2002). The reason for this has been suggested by a mathematical model of rates of change of antibiotic resistance among bacteria (Stewart et al., 1998). The conclusions from the model suggest that the period time to observe reductions in the incidence of antibiotic-resistant organisms will be longer than the preceding increases. Thus, it may be many years before sustained reductions in antibiotic use produce reductions in penicillin-resistant pneumococci. In addition, larger reductions in antibiotic use may be necessary to produce more rapid changes in resistance patterns. Assessing the full effect of reductions in community-wide antibiotic use may be made complicated by the already observed reductions in invasive pneumo-coccal infections in immunized children and their contacts due to conjugate pneumococcal vaccines.

In the studies of the use of delayed antibiotic prescriptions for URIs and otitis media, significant patient morbidity was not observed (Arroll et al., 2002; Dowell et al., 2001; Little et al., 2001). As the outcome of viral respiratory tract infections is not altered by antibiotics, these are not unexpected results for the studies of URIs. It is important, however, to have data that demonstrates this lack of morbidity for illnesses such as acute bronchitis and purulent rhinitis where the etiologic agent, while usually viral, is often thought to be bacterial by many practitioners. The demonstration that there is no benefit to immediate use of antibiotics may serve to convince many physicians and patients that antibiotics are not needed for these conditions. Delayed prescriptions for acute otitis media in children are frequently used in many European countries but have not gained popularity in North America. This pragmatic study (Little et al., 2001) demonstrates that waiting a few days to use an antibiotic among children diagnosed with otitis media does not increase morbidity from this disease. It has been argued that studies like this do not validly assess the effect of antibiotics on acute otitis media as the diagnostic criteria are not strict enough, leading to the inclusion of many patients who did not truly have bacterial otitis media; however, this argument only serves to strengthen the conclusions from this study that antibiotics are not required for most cases of acute otitis media diagnosed in the primary care setting most likely because this condition is overdiag-nosed. Withholding immediate antibiotic helps to weed out those children with URIs and red tympanic membranes from those with true bacterial middle ear disease, leading to more appropriate antibiotic use.

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