In this multi-centered study involving six Japanese medical institutes, we examined the antimicrobial prescriptions for patients diagnosed with uncomplicated cystitis. In comparison with the administrative claims database that reported that more than 90% of the antimicrobials prescribed for uncomplicated cystitis were either fluoroquinolones or third-generation cephalosporins , the proportion of broad-spectrum antimicrobials in our cohort was lower at approximately two-thirds of the eligible cases. The broad-spectrum agents were prescribed frequently in the older group (≥50 years) and to male patients. Neither age, sex, or antimicrobial types were associated with the recurrence of simple cystitis.
The primary aim of this study was to elucidate the rates of antimicrobial prescriptions for cystitis by directly drawing clinical data from medical records. Based on the health insurance claims data , fluoroquinolones (52.7%) and third-generation cephalosporins (36.9%) accounted for most of the prescriptions for female patients aged ≥15 years with uncomplicated cystitis. This result indicates that the prescription rates of broad-spectrum antimicrobial agents for cystitis in female patients reach nearly 90% in Japan. Our clinical database, however, demonstrated that the overall prescription rates of fluoroquinolones and third-generation cephalosporin were comparatively lower at 36.0% and 29.9%. Focusing on female patients, these broad-spectrum agents, namely, fluoroquinolones and third-generation cephalosporin were prescribed to 30.4% and 31.4% of the patients, respectively. Including faropenem, the prescription rate of broad-spectrum antimicrobials for simple cystitis in women was 65.4%, which was much lower than the data described in the administrative database study . A potential explanation for the differences in the prescription rates of broad-spectrum antimicrobials includes a discrepancy in patient demographics. In order to collect data for patients with uncomplicated cystitis, we used ICD-10 code N300 similar to that employed in the previous study . Thus, we believe that patients with similar clinical backgrounds could be recruited. Upon examination of the patient age, more than 80% of the patients in our cohort were aged ≥50 years, while more than half of the patients in the administrative data were aged <50 years. The high proportion of aged patients in our study may yield higher prescriptions of broad-spectrum antimicrobials, which, however, was not observed. While the previous study included teenagers (patients aged ≥15 years,) our study involved only those aged 20 years and more. This difference, however, would not influence the manner of prescriptions remarkably, considering the fact that fluoroquinolones are typically not recommended for pediatric patients by package inserts in Japan. Another factor for fewer prescriptions of the broad-antimicrobials may involve further promotion of AMS in the regions of medical institutes included in this study. However, this should be compared with similar studies conducted in different regions.
Among our patients, the broad-spectrum antimicrobials were prescribed frequently to patients in the high-age group, male patients, and those treated at the internal medicine department. In the previous study , the broad-spectrum antimicrobial prescription rates for simple cystitis were 91.1% in the young group (<50 years) and 90.1% in the older group (≥50 years), showing little difference. In contrast, in our results, the proportions of broad-spectrum antimicrobial prescriptions among the older and younger groups were 71.9% and 57.1% (OR, 95%CI; 1.83 [1.23 – 2.71]), indicating that aged patients were more likely to be prescribed broad-spectrum drugs. This could be rationalized by the fact that aged people tend to present more frequently with underlying diseases, conceivably leading to complicated or severe UTIs. This tendency of frequent prescription of more broad-spectrum drugs among the elderly has also been observed in other studies [11, 14, 15].
The differences in the prescription of broad-spectrum drugs between females (65.4%) and males (86.6%) should be discussed as well. Males do not typically contract cystitis owing to the anatomical advantage [16, 17]. The prevalence of UTIs in females is approximately 50 times higher than that in males . Thus, male patients with UTIs do present with certain underlying disorders, such as urinary tract stones/malignancy, neurogenic bladder, spinal cord injury, and post-kidney transplantation [18, 19]. Our observations of the significantly higher proportion of prescriptions of broad-spectrum drugs among male patients may be attributed to this dissimilarity between the sexes in terms of vulnerability to UTIs. Considering the limitations of the feasibility of the study, we did not collect detailed data of patient characteristics, and hence, could not adjust their backgrounds.
Of note, a single-facility study suggested that organisms isolated from patients visiting urologists with uncomplicated cystitis tend to show resistance to various antibiotics compared to hospital-wide antibiograms . Hence, a higher number of prescriptions of broad-spectrum drugs should have been observed at the Urology Department in our cohort. However, our investigation found significantly fewer prescriptions of broad-spectrum agents by urologists, which can be attributed to inter-facility or inter-physician differences. Future studies should incorporate these factors that potentially affect antimicrobial prescriptions.
Importantly, our multivariate analysis suggested that prescriptions of the broad-spectrum antimicrobials were not associated with the prevention of the recurrence of cystitis. In view of AMS, broad-spectrum drugs should not be prescribed for common diseases like simple cystitis. Particularly focusing on fluoroquinolones, they are widely active against the urinary pathogens, and a recent meta-analysis based on the systematic review of 47 randomized controlled trials demonstrated the superiority of the drugs compared to that of other antimicrobial agents in terms of clinical remission rates, bacteriological eradication, the emergence of resistance, and relapsing rates . A retrospective population-based cohort study based on administrative health data extracted from six Canadian provinces also verified the advantages of fluoroquinolone prescriptions, such as fewer revisits of outpatients and emergency patients, hospital admission, and re-prescription of antimicrobials within 30 days . However, fluoroquinolones have a variety of adverse drug effects, including QT elongation, glucose intolerance, retinal detachment, tendinitis, aortic aneurysm, and neurologic disorders . Also, the increasing trend of clinical isolations of fluoroquinolone-resistant organisms in UTIs has been corroborated by recent surveillance studies in Japan [12, 13, 20, 24, 25]. Although these facts may make us reluctant to treat patients with simple cystitis with fluoroquinolones, our data demonstrated that many such cases are still treated with the drugs. Our analysis, however, indicated that the administration of narrow-spectrum antimicrobials is not associated with the recurrence, supporting the safety of the treatment of patients with uncomplicated cystitis with amoxicillin, first- or second-generation cephalosporins, and sulfamethoxazole-trimethoprim.
The strength of the present study lies in the direct collection of clinical data from medical records. Previous larger studies were based on health insurance claims data , and therefore, the validity of the clinical diagnosis was unreliable. However, there are several limitations to this study. First, despite the multi-centered database, the data of our cohorts were derived merely from six medical institutes. Thus, the generalizability of the study should be evaluated by larger investigations. Second, the ages of the patients were higher with respect to cystitis, since cystitis is typically observed in a younger population. This could be attributed to the fact that we primarily collected data from regional hospitals in rural areas where the population is aging rapidly. Third, information essential to the selection of antimicrobials, such as the history of medication allergies, was not collected. Fourth, the ICD-10 codes given in the medical records may be labeled just for convenience so as to not interrupt their antimicrobial orders. Despite these downsides, our data was of help in comprehending the current practice of antimicrobial prescriptions for uncomplicated cystitis, which can be one of the cornerstones of AMS promotion.
In summary, amid the promotion of AMS to combat AMR, two-thirds of antimicrobials prescribed for cystitis were broad-spectrum agents, primarily fluoroquinolones or third-generation cephalosporin. Male gender, higher age, and visits to the internal medicine department were statistically associated with such prescriptions. Notably, prescriptions of broad-spectrum antimicrobials were not related to the prevention of recurrence. Our present finding would be an indicator for monitoring the antimicrobial prescriptions for patients with cystitis, which, we expect, can be useful data for health policymakers.