In this work, a CDSS interposed treatment guidelines at the time of electronic order entry for antibiotics frequently used for outpatients with ARI. We report that the indicated use of the two antibiotics targeted by the CDSS, azithromycin and gatifloxacin, remained undiminished, but that their unnecessary use for ARI was curtailed for a 4-year period. This outcome was not observed for antibiotics not subject to the CDSS at the intervention and at the control sites.
The strengths of our study include the long duration of the intervention, the large sample size, and explicit case definitions and treatment criteria. Statistical comparisons could be made not only across the pre vs. post intervention time period, but also between the targeted and non-targeted antibiotics. Because pre- and post-intervention data was available from the intervention and the control site, we could also use a quasi-experimental difference-in differences approach to control for factors other than the CDSS that could be contributing to time-dependent changes in congruence to ARI antibiotics guidelines. In absolute terms, the overall 9.5% post-intervention decline in unwarranted antibiotic use for ARI was consistent with the 9.7% median reduction observed in 30 conventional intervention trials reviewed by Ranji et al. 
. What was exceptional is that we could attribute this decline almost entirely to the only two antibiotics targeted by the CDSS. For these antibiotics, CDSS filtered utilization apparently as intended: azithromycin and gatifloxacin remained the most popular antibiotics when indicated for ARI, but were seldom used when not needed.
From a safety and tolerability standpoint, providers must be allowed to override the recommendations of a CDSS. This design requirement could have allowed providers to bypass the chief aim of the intervention, which was to convince them not to prescribe antibiotics unnecessarily for ARI. In a first scenario, they could have redirected ingrained misutilization to antibiotics not subject to the CDSS. Had this been the only effect of the intervention, we estimate that the proportion of ARI visits where antibiotics were not warranted but where agents other than azithromycin and gatifloxacin were prescribed should have risen above 50% in the post-intervention period. Because this proportion remained unchanged at 30%, our data argue that the CDSS did not merely shunt misutilization toward alternative, unrestricted drugs. In a second scenario, providers could have assigned the diagnosis of “pneumonia” more liberally, thereby seemingly justifying antibiotics that, in fact, were not indicated. Had providers used this tactic to justify all unwarranted prescription of the targeted agents, the proportion of all ARI visits where the targeted antibiotics were prescribed would have remained unchanged. In reality, this proportion decreased from 21.7% at baseline to 11.8% post-intervention. Providing further reassurance that outcomes were not due to systematic “gaming” of the process, subgroup analyses that either excluded patients with a pneumonia diagnosis or that included only patients whose sole diagnosis was acute bronchitis yielded findings comparable to those found in the full cohort. Overall, and even though unintended actions such as those outlined in the above scenarios could have occurred more than occasionally, our data suggest that the main effect of the CDSS was to extinguish unneeded prescriptions of the targeted agents.
Many factors could limit the generalizability of our results. The study did not employ a randomized allocation process, leaving it susceptible to well-described biases 
. The intervention was implemented at only one site, in the favorable context of a comprehensive health care system whose providers were familiar with prescription-based CDSS. As the difference in initial guideline-congruent prescribing between our two study sites illustrates, antibiotic prescribing may vary widely between sites 
. Thus, a process similar to the one described in this study may need adjustments, require significant provider education and yet yield different outcomes when implemented elsewhere. The retrospective data collection meant that symptoms and signs were assumed to be absent if they were not documented in the medical record. Thus, ARI episodes could have been missed or mislabeled, along with the rationale justifying the use of antibiotics. Although prior studies aimed at improving antibiotics utilization have returned similar results in VA and non-VA environments 
, our study population was mostly male and did not include pediatric age groups or patients with COPD. By focusing on initial visits for ARI, the study also did not address ARI patients returning to clinics with unabated or worsening ARI symptoms. Because multiple practitioners, from medical students to attending physicians, were often involved in assessing patients, we could not formally control for potential predictors of prescribing congruence such as individual practitioners’ prior practices, level of experience and exposure to the CDSS. These limitations represent design opportunities for future, hopefully prospective multisite studies aimed at determining how similar interventions based would fare when extended to more antibiotics or to other health care settings.
The rate at which antibiotics are inappropriately used for ARI remains high but has been decreasing for more than a decade 
. This decline, however, exhibits unfavorable features in an aging population: it has been concentrated in the pediatric population and may not be occurring at all in patients 50 years or older 
. The decline has also not affected all antibiotics equally, with ARI-related utilization of azithromycin and fluoroquinolones actually increasing 
. Thus, there is a continued need to develop better methods to improve ARI-related antibiotics use. CDSS have long proven capable to change prescribing practices, with most published applications directed at improving drug dosing 
and safety monitoring 
. CDSS have also shown the potential to improve utilization of antibiotics, particularly in the hospital environment 
. To date, however, examples of demonstrated utility in the outpatient arena remain scarce 
. In the only study that included adults with ARI 
, providers were given the opportunity to consult a stand-alone CDSS in order to receive patient-specific recommendations. Our intervention is distinctive in that our CDSS was neither stand-alone nor optional. Instead, the CDSS was incorporated into a comprehensive EMR and interposed in the normal workflow leading to an e-prescription. The CDSS also did more than issue recommendations: it either did or did not lead to order entry and recorded the prescribing rationale thereby imparting at least the possibility of future accountability to a process that was otherwise operating as an honor system. These features, which had been associated with CDSS effectiveness in other domains 
, were meant for the intervention to be stronger than what had previously been attempted for antibiotics stewardship purposes 
. Yet, the path illustrated here did not include the vigorous traditional approaches associated with larger effect sizes in past trials i.e. one-on-one interactions, concurrent order reviews or practice audits 
. Our results therefore raise the hope that, at least for outpatients with ARI, counteracting antibiotic abuse may not require time-consuming, ultimately unsustainable activities.
From a disease-management standpoint, this CDSS intervention stood at a disadvantage because it targeted only a minority of the agents that could be used to treat ARIs. The system could nevertheless have effected large changes in overall guideline-congruent prescribing for ARI if it had fostered the transmission of information from providers to providers. Two lines of reasoning suggest that extra-CDSS educational transmission was not a major outcome of this intervention: 1) congruence gains were attributable to improved utilization of the CDSS-targeted antibiotics only; and 2) those gains were realized in the first post-intervention year and did not further increase afterwards. Thus, prescribing congruence did not exhibit the gradual expansion that would have been expected from an increasing the proportion of providers familiar with the ARI guidelines. Whether or not these outcomes are particular to a teaching institution with rapid housestaff turnover, they serve as a reminder that much more work will be required before we know how to best design, target and integrate prescription-based interventions to optimize the overall management of ARI.