Case-based audit and feedback around a decision aid improved antibiotic choice and duration for uncomplicated cystitis in primary care clinics

Introduction

Antimicrobial resistance is a well-recognised threat to global health, with the USA alone accounting for 2.8 million antibiotic-resistant infections and 35 000 deaths each year.1 Increasing realisation of the need to minimise this public health threat can be seen in the efforts of regulatory bodies such as the Joint Commission, which recently established requirements for antimicrobial stewardship for ambulatory healthcare organisations, effective at the beginning of 2020.2 The new requirements mandate that such organisations provide resources to practitioners to promote appropriate antibiotic prescribing practices.2

Although most studies of outpatients have focused on implementing antibiotic stewardship for upper respiratory infections,3 4 there is also a high prevalence of inappropriate antibiotic prescribing for urinary tract infections (UTIs) in primary care, including overuse of fluoroquinolones and longer duration of treatment than recommended by guidelines.5–10 A study in France found that only 20% of outpatient UTIs were treated with the guidelines-recommended drug, dose and duration.11 An Irish study found that only 55% of the antibiotic prescriptions for UTI in general practice were appropriate.12 Of 7738 outpatient encounters for UTI in Israel, 91% were treated with a longer duration of antibiotics than recommended by guidelines.13 A recent US study revealed that fluoroquinolones were the most commonly prescribed antibiotics for uncomplicated UTI, comprising up to 49% of prescriptions.6 Inappropriate use of fluoroquinolones is especially concerning because it promotes the emergence and spread of multidrug-resistant Escherichia coli strain sequence type 131.14 In addition, continued overprescribing of fluoroquinolones for uncomplicated cystitis in patients with other treatment options is occurring in the USA5 15 despite two black-box warnings from the US Food and Drug Administration (FDA) for fluoroquinolones due to an association between their use and serious side effects.16–18 In addition, fluoroquinolones were associated with more central nervous system-related and gastrointestinal-related adverse events compared with other types of antimicrobials in a recent meta-analysis.19 Excessive treatment duration for uncomplicated cystitis is another common problem documented internationally.9 13 Current Infectious Diseases Society of America (IDSA) guidelines20 recommend nitrofurantoin for 5 days, trimethoprim–sulfamethoxazole for 3 days and a single dose of fosfomycin as the first-line regimens for uncomplicated cystitis. In our previous study in the same setting, most prescriptions for trimethoprim–sulfamethoxazole, nitrofurantoin and fluoroquinolones had a treatment duration longer than recommended.9

Unlike upper respiratory infections, which typically involve viral infections for which antibiotics are not indicated, a symptomatic UTI merits treatment with antibiotics, as recommended by the IDSA guidelines.20 Thus, the focus in implementing antibiotic stewardship for UTI needs to be optimisation of antibiotic choice and duration, which may present a different cognitive challenge for practitioners than deciding whether a patient needs antibiotics or not. One evidence-based strategy shown to be effective in implementing an antimicrobial stewardship for UTI in acute and long-term care settings is audit and feedback.21–23 Multiple strategies have been employed for implementing stewardship such as feedback to prescribers on antimicrobial consumption and antimicrobial stewardship committee.24 Based on our prior successful experience with audit and feedback in acute and long-term care,21 we implemented a multifaceted antimicrobial stewardship intervention using audit and feedback to improve compliance with acute cystitis guidelines in a family medicine setting (general practice). The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care. We hypothesised that our intervention would increase guideline adherence in terms of antibiotic choice and duration of treatment.

Methods

Study population

The study population included all patients with acute uncomplicated cystitis at the intervention and control sites. Inclusion criteria for uncomplicated cystitis required that participants be women ≥18 years who had International Classification of Diseases, Tenth Revision (ICD-10) codes (N30.0, acute cystitis; N30.9, cystitis unspecified; and N39.0 UTI site not specified) for UTI listed as a diagnosis in the EMR system (Epic Clarity database). In addition to a UTI-related diagnosis, patients must have also been prescribed a UTI-relevant antibiotic during the same visit. UTI-relevant antibiotics included fluoroquinolones, nitrofurantoin, fosfomycin, trimethoprim alone or in combination with sulfamethoxazole, beta-lactams and aminoglycosides. The electronic algorithm, using ICD-10 UTI diagnosis codes paired with medication data to identify patients with UTI, was validated in the same setting.26 Visits that met criteria for complicated UTI or had recorded signs or symptoms of pyelonephritis were excluded (eg, an additional code for genitourinary abnormalities or recorded fever, defined as ≥100.4°F or 38°C). We also excluded five patients who had allergies to both nitrofurantoin and sulfa-containing antibiotics and those prescribed long-term antibiotics indicating prophylaxis for recurrent UTI (figure 1).

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Figure 1

Selection process used to determine uncomplicated cystitis visits in the study period*. The study period was from July 2016 to February 2019. *Visits may have had more than one exclusion criteria. UTI, urinary tract infection; ICD, International Classification of Diseases.

For each eligible visit, we extracted the following variables: patient age, race, comorbidities (Charlson Comorbidity Score), antibiotic allergies, type of antibiotic prescribed and duration of treatment. If a patient returned to the clinic within 7 days of initial treatment due to UTI, the case was considered as a failure of previous treatment. In these cases, only the original visits were included in the study. We included women with diabetes because recent evidence suggests that diabetic women presenting with acute cystitis in primary care should be managed similarly to women without diabetes.27 We also included women aged ≥65 years, as treatment recommendations for otherwise healthy older women are similar to those for younger women.20 Each record was manually reviewed by a team member (GG or MG) to rule out the possibility of contraindication to all first-line antibiotics. All cases of acute uncomplicated cystitis during the study period were included in the analysis.

Outcome measure

The outcome of this study was in adherence to the IDSA guidelines for managing uncomplicated cystitis, both to medication choice and duration of therapy (figure 2). For example, prescribing a guideline-adherent antibiotic (nitrofurantoin) for excessive duration (7 days) would be counted as non-adherent. Likewise, prescribing ciprofloxacin (a non-first-line antibiotic choice) for the correct duration (3 days) would be counted as non-adherent. Prescribing a first-line agent (trimethoprim–sulfamethoxazole) for the correct duration (3 days) would be counted as compliant. Likewise, prescribing nitrofurantoin for 5 days or a single dose of fosfomycin would be counted as compliant.20

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Figure 2

Pocket card on choosing empirical antibiotic treatment for acute cystitis based on Infectious Diseases Society of America guidelines. bid, two times per day.

Results

Figure 1 is a flow chart showing the study selection process to identify eligible visits with acute uncomplicated cystitis in the study period. After applying our prespecified exclusion criteria, our final sample included 932 visits representing 812 unique patients. Of these 932 visits, 546 were made at the intervention clinic and 386 at the control clinic. Table 3 presents the characteristics of patients at intervention and control clinics. Patients with uncomplicated cystitis visiting the control clinic were slightly younger than those in the intervention clinic (46.8 years versus 49 years). In both clinics, most patients were Caucasian (62.5% and 54.9%, respectively), followed by black, Asian and Hispanic patients. No significant differences were observed for race/ethnicity or Charlson Comorbidity Index.

Discussion

In this difference-in-differences study, we implemented a multifaceted stewardship intervention that targeted inappropriate antibiotic choice and duration of treatment. An increased proportion of guideline-adherent prescriptions was observed in the intervention period of both intervention and control sites. However, in the difference-in-differences analysis, the intervention site had a significantly larger increase in adherence than the control site.

The audit and feedback stewardship intervention was successful for UTI treatment in emergency departments22 33 and acute21 23 and long-term care.21 In this study, we applied the audit and feedback intervention to primary care settings, where antibiotic stewardship is urgently needed.2 34 Our intervention was based on a treatment algorithm derived from the IDSA guidelines and AAFP recommendations on management of uncomplicated UTI.20 25 Our qualitative study showed that differentiating uncomplicated cystitis from other UTI syndromes is a challenge for providers28; therefore, providing a set of diagnostic criteria for uncomplicated cystitis was important. This treatment algorithm describes steps that providers should take when encountered with a patient with UTI-relevant symptoms. We used this algorithm as a starting point to provide personalised, interactive, one-on-one feedback with providers to improve their capacity to distinguish between uncomplicated and complicated UTI and treat UTI appropriately. The content was individualised for each recipient, and specific information about the correct solution was included to maximise feedback effectiveness.30 Besides improvements in the clinical outcomes, we also observed that the intervention was received positively by feedback recipients.

Positive impacts of antibiotic stewardship interventions in the inpatient setting and emergency department have been well described.21–23 33 In contrast, fewer studies describe successful implementation of UTI antibiotic stewardship strategies in the US outpatient setting, where an estimated 80% of antibiotic use occurs.35 A previous study in a family medicine setting used a decision support tool embedded in the EMR to improve guideline adherence for uncomplicated UTI.36 However, the utilisation of the tool clinic-wide was only 29%. Our study, one of the first to use audit and feedback in family medicine, suggests that audit and feedback is an effective approach to antibiotic stewardship in outpatient primary care clinics, although it is labour intensive.

Our study has some limitations. First, we observed improved outcomes not only in the intervention site but also in control site, which may be due to spillover effect from the providers in the intervention site to their colleagues at the control site. The clinics are in the same geographical area, and the providers from both clinics have regularly scheduled faculty meetings. Another reason for improved outcomes at the intervention and control site may be the release of FDA warnings against fluoroquinolones in the intervention period, which may have contributed to avoidance of fluoroquinolones and increased adherence to the guidelines. However, in our previous interrupted time series analysis in the same setting, the 2016 FDA boxed warning against fluoroquinolone use for simple infections was not associated with a significant reduction in the rate of fluoroquinolone prescriptions for UTI.5 Second, we assessed the choice of antibiotics and duration of therapy as these aspects of the regimen had low concordance in our previous database study in the same clinics.9 We did not assess dose or frequency of antibiotics. Third, our study was conducted only at two clinics within the same healthcare system, and certain modifications might be needed for other healthcare systems such as public healthcare system. The proportion of guideline-adherent prescriptions at baseline was higher in the intervention site. This may be explained by a lower number of visits with uncomplicated cystitis in the baseline period in the control site, so the baseline difference between the clinics may be an artefact of small sample size. Local prescribing culture and social norms may have also contributed to the baseline differences in the outcome between the clinics; culture has been previously shown to lead to differences in antibiotic prescribing in other studies.37 38 However, different levels of outcome at baseline are acceptable for difference-in-differences analysis.39 There is no requirement that guideline-concordant prescriptions should be similar at baseline,39 and our data meet the parallel trend requirement for difference-in-differences analysis. Fourth, we did not perform a formal evaluation of implementation fidelity. Fifth, our quasi-experimental study was not randomised, and we did not evaluate sustainability of the intervention. Perhaps most importantly, we noted that providing individualised audit and feedback is time-consuming and presents sustainability challenges.

Conclusion

In this difference-in-differences study, we demonstrated that our multifaceted stewardship intervention can improve the proportion of primary care clinic visits for UTI in which women receive the right drug with the right duration, a fundamental aspect of antibiotic stewardship. Future dissemination of this intervention to additional primary care clinics may incorporate a component of computerised decision support built around our UTI treatment algorithm, in addition to case-based audit and feedback, to facilitate scale-up and sustainability.