Practitioner Education and Feedback to Decrease Ciprofloxacin Prescriptions in Patients with Acute Uncomplicated Cystitis


Richard F Guo, MD; Dinh L Nguyen, MD; Steven Park, MD;
Kristen Nguyen, MD; Steven Ko, MD; Vicki Y Chiu, MS;
Jana Dickter, MD; Davida Becker, PhD MS;
Philomena Cho, MD

Perm J 2020;24:18.036 [Full Citation]
E-pub: 12/30/2019


Context: Current guidelines recommend a nonfluoroquinolone agent as first-line treatment of acute uncomplicated cystitis (AUC) because of concerns of antimicrobial resistance and adverse effects.
Objective: To test whether a multifaceted intervention involving education and feedback reduced primary care practitioners’ ciprofloxacin prescriptions for AUC therapy.
Design: Primary care practitioners at 3 medical offices participated: 65 in the intervention group and 51 in the control group. Intervention group participants received an educational lecture and emailed summary of antimicrobial guidelines, their AUC prescriptions were audited, and feedback was provided on inappropriate antibiotic choices. Prescriptions at AUC encounters were tracked during baseline, intervention, and postintervention periods.
Main Outcome Measures: Proportion of AUC encounters at which ciprofloxacin was prescribed vs recommended first-line antibiotics.
Results: Intervention group participants had 5262 eligible AUC encounters, and control group participants had 5473. At baseline, ciprofloxacin was prescribed at 29.7% and 33.7% of eligible AUC encounters in the intervention and control groups, respectively (p = 0.003). After intervention, ciprofloxacin was prescribed at 10.8% of eligible AUC encounters in the intervention group and 34.3% in the control (p < 0.001). Adjusted odds ratios of ciprofloxacin prescription for AUC therapy were significantly lower in the intervention group during postintervention and intervention periods vs baseline (0.29, 95% confidence interval = 0.20-0.44, p < 0.001 and 0.80, 95% confidence interval = 0.66-0.97, p = 0.03). Adjusted odds ratios did not change over time in the controls.
Conclusion: Educating primary care practitioners and conducting audit and feedback reduced their prescriptions of ciprofloxacin for AUC therapy.


Antimicrobial resistance is estimated to contribute $20 billion per year in excess direct health care costs.1 As a result, state and federal agencies in the US have made antimicrobial stewardship programs (ASPs) a priority to address emerging resistance.2 The benefits of antimicrobial stewardship have been well documented and implemented in the inpatient and Emergency Department settings.3-5

At the Kaiser Permanente (KP) Fontana Medical Center in Fontana, CA, and the KP Ontario Medical Center in Ontario, CA, an inpatient ASP led by a dedicated infectious disease pharmacist has been in place for more than a decade. The pharmacist’s role is to review inpatient antibiotic choices and to make adjustments and recommendations, as appropriate, on the basis of national guidelines, local sensitivity data, and patient-specific comorbidities, such as renal failure. The typical changes that are made include converting antibiotic regimens from intravenous to oral, narrowing the spectrum of antibiotics, and limiting the length of therapy as recommended by national guidelines. In particular, the program has chosen to focus on fluoroquinolones such as ciprofloxacin as one of the most commonly misused antibiotic classes in the inpatient setting, with successful reduction in their use. Since the beginning of the ASP, the local overall use of broad-spectrum antibiotics such as antipseudomonal agents has been significantly reduced by 15% to 22% as measured by days of therapy based on internal metrics.

Most antibiotic prescriptions, however, occur in outpatient settings or long-term care facilities, where high prescription volume makes it difficult to implement the same strict monitoring and oversight by the infectious disease pharmacist that happens in the inpatient setting. In the outpatient setting, one of the leading diagnoses for which ciprofloxacin is prescribed is acute uncomplicated cystitis (AUC), also known as uncomplicated urinary tract infection (UTI). The 2010 Infectious Diseases Society of America (IDSA) guidelines define the condition in women as lower urinary tract symptoms in women aged 18 to 65 years, who are not immunosuppressed, are not pregnant, do not have anatomical abnormalities, and are not receiving dialysis.6 Although IDSA guidelines do not specifically address UTI management in patients with diabetes, experts suggest that in patients with well-controlled diabetes without urological sequelae, the same antimicrobial regimens for AUC can be initially tried.

The IDSA guidelines recommend the use of nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin, or pivmecillinam (not available in the US) as first-line therapy for AUC. Fluoroquinolones are efficacious, but they have the potential for substantial collateral damage from antibiotic resistance and secondary infections such as Clostridium difficile, which are more common with fluoroquinolone use compared with other antibiotic classes.6,7 In July 2016 the US Food and Drug Administration advised that serious adverse effects have been associated with fluoroquinolone use and the risks typically outweigh the benefits for patients with uncomplicated UTIs who have alternative treatment options.8

Research nationally indicates that 80% of patient visits for uncomplicated UTIs involve an antibiotic prescription, and the most commonly prescribed antibiotics are fluoroquinolones (49%).9 Although generally effective, ciprofloxacin is not recommended as first-line therapy. According to IDSA guidelines, ciprofloxacin should be reserved for more complicated scenarios than AUC and, when used for AUC, should be considered only as an alternative or as salvage antimicrobial therapy when first-line therapy has failed.

Studies have found that outpatient ASPs that combine education, oversight, and frequent feedback can decrease the prescribing of inappropriate antibiotic therapy.4,5,10 However, most ASP studies have focused on acute respiratory tract infections.5 A handful of studies describe educational programs to decrease primary care physicians’ inappropriate antibiotic prescribing practices for treatment of UTIs, but these studies were conducted decades ago.11-13 A few more recent studies describe ASP programs for UTIs implemented in Emergency Department settings.14,15 Given the limited recent studies on the effectiveness of outpatient ASP programs for AUC, we tested whether a multifaceted educational intervention improved primary care practitioners’ antibiotic prescribing for patients with AUC. We hypothesized that educating clinicians on the IDSA guidelines and conducting audit and feedback of their AUC prescriptions would reduce the proportion prescribing ciprofloxacin for AUC therapy and would result in more appropriate ciprofloxacin use.


The KP Fontana Medical Center is an integrated medical center located in the Inland Empire region of California and is supported by many satellite medical offices. These medical offices are geographically close, draw on a similar patient population, are under the same physician leadership, and are governed by the same workflow protocols. Outpatient encounters in the medical offices and the main medical center are staffed by internal medicine physicians, family medicine physicians, physician assistants, and nurse practitioners who are based solely in that medical office.

The study drew from 3 such medical offices in the regional service area. Participants enrolled included all physicians, nurse practitioners, and physician assistants in the Internal Medicine and Family Medicine departments. Medical residents were excluded because of the low volume of patients seen by each resident. For a similar reason, per diem and temporary staff were excluded. Practitioners from 2 of these medical offices together formed the control arm for the study. Practitioners from the third and largest medical office formed the intervention group. A nonequivalent control group study design was chosen over individually randomizing practitioners to intervention and control groups to minimize the risk of cross-contamination between enrolled practitioners in the same medical office, who often share educational practices and patients. All practitioners initially enrolled in the study were followed-up until study end. New practitioners joining the medical offices after the study’s start date were not enrolled. Internal transfers of practitioners already enrolled were an exception. One clinician who switched between medical office sites in the study was retained in the initial assigned group.

Practitioners in the intervention group were exposed to a multifaceted educational intervention conducted from January 1, 2015, to August 31, 2015. First, they received an hour-long, on-site, in-person educational lecture session by an infectious disease specialist, reviewing the IDSA and regional guidelines for antimicrobial treatment choice for AUC. Two such mandated sessions during the lunch hour were conducted to expose practitioners to this information. Immediately after the presentation, an email with the presentation slides and a summary of antimicrobial choice guidelines was sent to practitioners. For the remainder of the intervention, the AUC prescriptions of practitioners in the intervention group were audited. Practitioners who had any cases of inappropriate ciprofloxacin prescriptions received monthly phone calls summarizing each case and providing recommendations. A script was used to provide standardized information during these calls.

Control group participants were not contacted or provided education, but their ciprofloxacin prescriptions were tracked. Before this study, no formal educational activities had been conducted to educate practitioners and staff on the IDSA guidelines.

All office-based, phone, and urgent care patient encounters of the study participants were evaluated over 3 periods: A baseline period lasting 12 months (January 1, 2014-December 31, 2014), during the 8-month intervention (January 1, 2015-August 31, 2015), and for 7 months after the intervention (September 1, 2015-March 31, 2016). All antibiotics prescribed for AUC treatment were tracked during these periods. Encounters were generated from pharmacy prescription records, which attach an International Classification of Diseases (ICD) diagnosis code to antibiotic prescriptions. We obtained data for all ICD codes of cystitis or UTI. These data were then filtered to limit records reviewed to practitioners enrolled in the study, patient age 18 to 65 years, and female sex. This formed the inclusion dataset. The dataset was further filtered to generate a subset for manual review, selecting for prescriptions for ciprofloxacin. The medical records were manually reviewed for exclusion criteria of complicated UTI: Pregnant at time of medical office visit, end-stage renal disease (defined as glomerular filtration rate < 15 mL/min), history of anatomical abnormalities of the urinary tract, and a clinical diagnosis of pyelonephritis incorrectly coded as AUC. Encounters of AUC for which there was no prescription attached were not studied. Nonciprofloxacin prescriptions for AUC therapy were tracked but not manually reviewed.

Each encounter for which a prescription of ciprofloxacin was attached to a diagnosis code suggesting AUC was reviewed in detail. In addition to screening for exclusion criteria, a determination was made whether the prescription of ciprofloxacin was appropriate or inappropriate using a standardized flowsheet (Figure 1). Ciprofloxacin use was defined as “inappropriate” when the patient had no contraindications (through prior urine culture resistance patterns, medication intolerance, contraindications, or allergies) to any single preferred first-line agent (nitrofurantoin, trimethoprim-sulfamethoxazole, and cephalexin). Cephalexin, although not a first-line choice per the IDSA guidelines, was deemed preferred over ciprofloxacin by the regional Infectious Disease Department, because of local resistance patterns. Although fosfomycin is considered an appropriate first-line agent by the IDSA, it was not available in the local formulary and was available only after infectious disease consultation.

According to IDSA guidelines, a correct dosage of ciprofloxacin for AUC therapy was defined as 250 mg daily. Prescriptions of 500 mg daily or 750 mg daily were considered incorrect dosages. A prescription duration of 3 days or less was considered a correct duration. Prescriptions for duration longer than (but not shorter than) 3 days were considered inappropriate duration. Data were also collected on each clinician’s age, sex, level of training, years in practice, specialty (family medicine vs internal medicine), and profession (physician vs nurse practitioner or physician assistant), as well as the patient’s age. The study protocol was reviewed and approved by the KPSC institutional review board.

The primary outcome was any prescription of ciprofloxacin for AUC treatment, measured at the patient encounter level. Secondary outcomes were the appropriateness of ciprofloxacin when prescribed, including whether it was an appropriate choice and whether the dose and duration of therapy were appropriate.

We used descriptive statistics to summarize baseline characteristics of participants in the intervention and control groups as well as eligible patient encounters. For continuous variables, the mean, standard deviation, median, interquartile range, and minimum, and maximum are provided. For categorical variables, the frequency and percentage are presented. To test for differences in baseline characteristics of intervention and control groups, we performed t-tests and/or Kruskal-Wallis tests for continuous variables and c2 tests for categorical variables.

We then conducted multiple logistic regression analysis with repeated measures on practitioners to account for clustering of patient encounters within practitioners. The model estimated adjusted odds ratios (AORs), 95% confidence intervals (CIs), and p values for ciprofloxacin prescription at AUC encounters. The model controlled for intervention group (intervention vs control), period (baseline, intervention, postintervention), interaction between the intervention group and period, clinician’s age, sex, specialty (family medicine vs internal medicine), professional role (physician vs nurse practitioner or physician assistant), and patient’s age. After fitting the regression model, we conducted hypothesis tests to compare odds ratios across study groups and periods. We conducted c2 tests to test for differences in secondary outcomes at each period.

We estimated the sample size for the study so we could detect a reduction in prescribing of ciprofloxacin from 90% to 60%, with 80% power and a significance level of 5%. We determined we needed at least 32 practitioners in each study arm (nQuery Advisor version 8, Statistical Solutions Ltd, Boston, MA).



A total of 51 practitioners were in the control group, and 65 were in the intervention group. Practitioners in both groups were comparable in terms of age, sex, specialty, and length of employment (Table 1). Compared with the control group, the intervention group included a higher percentage of nurse practitioners and physician assistants (3.9% vs 20.0%, p = 0.01). At baseline, the mean number of AUC prescriptions written was higher among the control group participants compared with the intervention group (45.0 vs 34.9, p = 0.01). Practitioners varied in terms of their baseline rate of prescribing ciprofloxacin for AUC therapy from 0% of encounters to 94%, with a mean ciprofloxacin prescription rate of 31.3% of AUC encounters among intervention group participants and 30.8% among control group participants (p = 0.95).

In the intervention group there were 5262 eligible encounters at which AUC was diagnosed during the study period, and in the control group there were 5473. At baseline, the percentage of AUC encounters at which ciprofloxacin was prescribed was lower in the intervention compared with the control group (29.7% vs 33.7%, p = 0.003; Table 2). After the intervention, the percentage decreased to 10.8% in the intervention group, whereas in the control group it was 34.3% (p < 0.001). The monthly percentages of AUC encounters at which ciprofloxacin was prescribed are displayed in Figure 2 for both study groups.

Results from the repeated-measures multiple logistic regression model indicated that the AORs of ciprofloxacin prescription for AUC therapy were significantly lower in the intervention group during the postintervention and intervention periods compared with baseline (AOR = 0.29, 95% CI = 0.20-0.44, p < 0.001 and AOR = 0.80, 95% CI = 0.66-0.97, p = 0.03, respectively; Table 3). There was no difference in the odds ratios in the control group comparing the baseline period with the intervention or postintervention periods. The AORs of ciprofloxacin prescription for AUC treatment were lower in the postintervention period for the intervention group compared with the control group (AOR = 0.27, 95% CI = 0.15-0.47, p < 0.001). However, there were no differences in AORs between the intervention group and the control group during the intervention period.

For AUC encounters at which ciprofloxacin was prescribed, a detailed medical record review determined that in most cases it was given inappropriately because no contraindications to a first-line choice existed. At baseline, 91.6% and 92.9% of ciprofloxacin prescriptions in the intervention and control groups, respectively, were given inappropriately (p = 0.39; Table 4). The percentage of ciprofloxacin prescriptions that were inappropriate remained high throughout the study (> 80%), and although inappropriate use of ciprofloxacin was lower in the intervention group compared with the control group during the intervention period (90.0% vs 94.7%, p = 0.02), there was no significant difference between the groups after the intervention. Use of inappropriate ciprofloxacin dose and prescription durations (longer than necessary) were at or above 80% for the entire study period, and there were no significant differences between the intervention and control groups over the intervention or postintervention periods.


In this nonequivalent control group study, we found that  professional education combined with intensive prescription monitoring and feedback resulted in a significant reduction in primary care practitioners’ prescriptions of ciprofloxacin for AUC treatment and shifted practitioners toward using IDSA-recommended first-line antibiotics for AUC therapy. This finding is comparable to the results of other ASP studies.11,14-16

We hypothesize that the greatest impact of our education efforts was from making the monthly phone calls to practitioners, because we saw a gradual reduction of ciprofloxacin use during the postintervention period as opposed to the sharp drop that one would expect if all the reduction accrued from the lectures and emails. However, the study was not designed to differentiate between the effectiveness of different methods of intervention. A further study could be done with different groups of health care professionals being subject to different forms of intervention to determine the most effective one.

Similar to prior studies, we discovered a high frequency of inappropriate initial patterns of prescribing behaviors for AUC, underlining the importance of developing practitioner interventions and an outpatient ASP to improve patient care and cost savings. This may reflect ingrained habits and barriers to change in the health care professional community.17,18 During our monthly phone debriefing with practitioners, we found barriers such as outdated knowledge, lack of office visit time to do in-depth medical record review, patient preference for nonrecommended antibiotic therapy, and practicing defensive medicine (practitioner preference to use a stronger antibiotic “just in case”). Some practitioners raised concerns that during a certain encounter there was concern for upper UTI (complicated UTI) necessitating a different antibiotic choice, even though the supporting evidence for such a concern was not documented in the encounter notes.

Although we achieved a statistically significant reduction in the proportion of overall ciprofloxacin use, our secondary endpoints of correct ciprofloxacin use, dose, and duration did not similarly improve. Indeed, the proportion of use labeled as inappropriate remained high during the entire study period for both groups. This result may reflect the fact that some practitioners were not exposed to the educational intervention or were exposed but were reluctant to change their prescribing practices. A previous study of physicians’ attitudes about an intervention to support evidence-based prescribing found that some believed the intervention threatened their perceived need for clinical autonomy, whereas others reported that time pressures and information overload affected their ability to participate in the intervention or adopt the recommended behavior changes.19 It is possible that a different approach is needed to reach and change the behaviors of the practitioners who continued to prescribe ciprofloxacin for AUC treatment.

Our intervention relied on physicians to conduct the audit and feedback. The cost of the intervention might be reduced if staff other than physicians conducted the audit and feedback, for example, clinical pharmacy specialists. Additionally, clinical decision support tools might be a less costly intervention approach,14 because such tools do not require ongoing staffing. Since our study was conducted, a clinical decision tool has been implemented with the aim of improving evidence-based prescribing for treatment of uncomplicated UTIs.

KP is an ideal organization in which to conduct a wide-ranging intervention and study like this. Practitioners are integrated into a large medical group, and there is a centralized mechanism of distributing information about the latest medical advances and changes in guidelines. Because all practitioners in the KPSC Region are required to transmit prescription orders to plan-owned pharmacies through the electronic medical record, a consistent and reliable pool of retrievable prescription data is created. After collecting prescription data on antimicrobial prescription orders during the study period, our study team was easily able to link the orders with the associated office encounter, filter the encounters by ICD codes, and review the clinical decision making for each encounter. However, this may limit the feasibility of widespread adoption of this method in nonmanaged care organizations.

Our study has several limitations. Previous studies on antimicrobial stewardship showed that once the intensive monitoring programs end, the prescribing habits of the primary care practitioners almost always return to the previous baseline.4 Although we tracked participants for 7 months after the intervention, we did not continue tracking beyond this point. It is possible that physicians’ prescribing behaviors reverted to their level at baseline after the postintervention period ended, given the absence of ongoing intensive monitoring and feedback.

Our method for obtaining the aggregate data for prescriptions was to filter the patient encounters by matching ICD codes for AUC with antibiotic prescriptions. As such, it is possible that the improvement captured by the data is the effect of better documentation and proper coding. Practitioners who had previously coded a generic code for UTI to represent both complicated and uncomplicated UTIs may have coded more specifically as uncomplicated cystitis and pyelonephritis. If practitioners who were exposed to the intervention were more likely to improve their coding compared with those in the control group, this would have introduced biases into our results. Because ICD codes for complicated upper UTIs were not included by our filters, we could not measure whether there was a shift in diagnostic coding accounting for the decrease in the ciprofloxacin prescription rate.

In addition, the study used a nonequivalent control group design, not randomization, to assign practitioners to study groups, and the practitioners were not blinded. This design was chosen because of the difficulty of blinding given the need to provide ongoing feedback and the risk of cross-contamination within the medical offices as clinicians interacted with their colleagues at lunch and departmental meetings. Although practitioners are assigned to work at a specific site, there remains a possibility of cross-contamination between practitioners across different sites, because we could not ensure that they did not communicate.


Our study results found that a simple intervention of education, prescription monitoring, and feedback was associated with reduced ciprofloxacin prescriptions for AUC therapy among primary care practitioners, resulting in greater adherence to national and regional treatment guidelines. Our research findings highlight the need for outpatient ASPs and illustrate that they can be successfully implemented. Continued development and evaluation of outpatient ASP programs is critical.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


This study is supported by a grant from the Regional Research Committee of Kaiser Permanente Southern California.

We thank the staff of the Pharmacy Department at Kaiser Permanente Fontana Medical Center for providing the raw prescription data used in this study.

Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

How to Cite this Article

Guo RF, Nguyen DL, Park S, et al. Practitioner education and feedback to decrease ciprofloxacin prescriptions in patients with acute uncomplicated cystitis. Perm J 2020;24:18.036. DOI:

Author Affiliations

1 Department of Hospital Medicine, Kaiser Permanente Northwest, Portland, OR
2 Department of Family Medicine, Kaiser Permanente San Diego Medical Center, CA
3 Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, CA
4 HealthCare Partners, Long Beach, CA
5 University of Arkansas for Medical Sciences, Little Rock
6 Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena
7 Division of Infectious Diseases, City of Hope, Duarte, CA
8 Department of Graduate Medical Education, Kaiser Permanente, Pasadena, CA
9 Department of Internal Medicine, Kaiser Permanente Fontana Medical Center, CA

Corresponding Author

Dinh L Nguyen, MD (

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Keywords: ambulatory care, antibacterial agents, antibiotic stewardship, antimicrobial stewardship, ciprofloxacin, health personnel/education, medical audit, primary health care, professional practice gaps, urinary tract infections


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