Setting
MetroHealth Medical Center is a 650-bed tertiary care hospital in Cleveland, Ohio. The hospital has training programs for residents in internal medicine, family practice, obstetrics and gynecology, and several surgical subspecialties. The fluoroquinolones on formulary are ciprofloxacin and moxifloxacin. Fluoroquinolones are routinely prescribed for prophylaxis prior to invasive urologic procedures, but not for prophylaxis of other procedures or conditions. The hospital does not have a formal antimicrobial stewardship program and there are no restrictions or specific guidelines on fluoroquinolone use. However, pharmacists are assigned to some hospital wards to make antimicrobial recommendations regarding appropriate dosing, potential medication interactions, and potential allergic reactions. Pharmaceutical company representative are allowed to sponsor educational programs for trainees in the hospital and provide promotional materials, but are not allowed to give presentations related to their products. During the year of the study, the percent susceptibilities of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae to ciprofloxacin were 84%, 75%, and 95%, respectively. The percent susceptibility of E. coli to trimethoprim-sulfamethoxazole was 81%.
Study Design
We prospectively examined the necessity of oral and parenteral fluoroquinolones administered to adult inpatients during a 6-week period in May and June 2009. The study design was based on a previous study of unnecessary use of antimicrobials in our facility [11]. Patients receiving new prescriptions for fluoroquinolones were identified through daily review of pharmacy records. If 10 or less patients received new prescriptions for fluoroquinolones on a given day, all patients were enrolled. If more than 10 patients received new prescriptions, 10 patients were randomly selected to be included in the study using a random number generator. Patients were allowed to be enrolled more than once if they received a second fluoroquinolone regimen at least 4 weeks after completion of the initial regimen. The study wards included 6 medical wards, 3 surgical wards, 3 intensive care units, 1 rehabilitation ward, 1 subacute skilled nursing ward, 1 psychiatric ward, 1 obstetric/gynecologic ward, and the emergency department. Information regarding demographics, admitting service and ward, indication for antimicrobial therapy (prophylaxis versus treatment), concurrent antimicrobials, clinical syndrome being treated, laboratory data, vital signs, radiological tests, and complications of therapy was obtained through medical record review and recorded on a standardized data collection form. Patients were followed through their entire hospital course, including transfers between hospital units.
Patients' medical records were reviewed at least once during the course of antimicrobial therapy and again six weeks after completion of therapy to assess whether possible complications or adverse effects of unnecessary therapy occurred. The frequency of adverse effects was calculated for all unnecessary fluoroquinolone regimens and for those unnecessary regimens in which fluoroquinolones were administered as monotherapy. Colonization or infection with a resistant pathogen (i.e., fluoroquinolone-resistant gram-negative bacillus, vancomycin-resistant enterococci [VRE], or methicillin-resistant Staphylococcus aureus [MRSA]) was considered a possible complication of therapy only if the patient did not have a history of colonization or infection with these organisms prior to the start of fluoroquinolone therapy; no routine surveillance for VRE or MRSA was conducted during the study period.
Infectious diseases specialists (M.T.H. and C.J.D.) determined whether the fluoroquinolone regimens were necessary or unnecessary. A fluoroquinolone regimen was defined as unnecessary if no antimicrobial therapy was indicated for the condition being treated or if the fluoroquinolone component of a regimen was not indicated. If the fluoroquinolone was determined to be necessary, additional assessments were made regarding whether part of the fluoroquinolone regimen was unnecessary. Part of the fluoroquinolone regimen was considered unnecessary if the duration of therapy was longer than recommended, the fluoroquinolone provided redundant antimicrobial coverage in the absence of an indication for combination therapy, the fluoroquinolone provided inadequate coverage of expected or documented pathogens, and if the fluoroquinolone was continued despite negative evaluation for infectious syndromes and/or a noninfectious condition was demonstrated to be responsible for the clinical syndrome.
The determination of the necessity of the prescribed fluoroquinolones was based on standard practice guidelines for management of infectious diseases developed and/or endorsed by the Infectious Diseases Society of America [13]. For example, current guidelines for asymptomatic bacteriuria recommend treatment only for pregnant women or individuals undergoing invasive urologic procedures [14]; to diagnose asymptomatic bacteriuria we required documentation that urinary symptoms were not present. If standard practice guidelines were not available, diagnostic and treatment recommendations from a current textbook of infectious diseases were used [14]. Hospital-acquired infections were defined by Centers for Disease Control and Prevention criteria [15]. If fluoroquinolones were considered necessary, we determined if there was an equally effective alternative agent that could have been prescribed. The rationale was to provide an estimate of how much fluoroquinolone use could be safely reduced if a hospital chose to implement a program of complete restriction of fluoroquinolones in an effort to control C. difficile or resistant gram-negative bacilli.
To determine the contribution of fluoroquinolones to total antibiotic use in the hospital, we examined pharmacy records for all antibiotics prescribed during the study period. The proportion of total antibiotic use (days of therapy) that was made up of fluoroquinolone use was calculated. In addition, for the year of the study, we estimated the costs of all fluoroquinolone therapy and of the unnecessary fluoroquinolone therapy based on average wholesale prices and on acquisition costs for the hospital.
Statistical analysis
Data were analyzed with the use of SPSS statistical software version 10.0 (SPSS Inc., Chicago, IL) and STATA 9.1 (StataCorp, College Station, TX). Bivariate analyses were performed to compare necessary and unnecessary treatment regimens. Continuous data were analyzed using student's unpaired t-tests. Categorical data were assessed using Pearson Chi-square test or Fisher's exact test. The hospital's institutional review board approved the study protocol and waived the requirement for informed consent due to the observational nature of the study.