Association of Adverse Events With Antibiotic Treatment for Urinary Tract Infection

Abstract

Background: Little is known about the relative harms of different antibiotic regimens prescribed to treat uncomplicated urinary tract infection (UTI). We sought to compare the risk of adverse events associated with commonly used oral antibiotic regimens for the outpatient treatment of uncomplicated UTI.

Methods: Using data from the IBM® MarketScan® Commercial Database, we identified 1 169 033 otherwise healthy, nonpregnant women aged 18-44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens from 1 July 2006 to 30 September 2015. We used propensity score-weighted Kaplan-Meier methods and Cox proportional hazards regression models to estimate the association between antibiotic agent and adverse events.

Results: Of 2 first-line agents, trimethoprim-sulfamethoxazole (vs nitrofurantoin) was associated with higher risk of several adverse drug events including hypersensitivity reaction (hazard ratio, 2.62; 95% confidence interval, 2.30-2.98), acute renal failure (2.56; 1.55-4.25), skin rash (2.42; 2.13-2.75), urticaria (1.37; 1.19-1.57), abdominal pain (1.14; 1.09-1.19), and nausea/vomiting (1.18; 1.10-1.28), but a similar risk of potential microbiome-related adverse events. Compared with nitrofurantoin, non-first-line agents were associated with higher risk of several adverse drug events and potential microbiome-related adverse events including non-Clostridium difficile diarrhea, C. difficile infection, vaginitis/vulvovaginal candidiasis, and pneumonia. Treatment duration modified the risk of potential microbiome-related adverse events.

Conclusions: The risks of adverse drug events and potential microbiome-related events differ widely by antibiotic agent and duration. These findings underscore the utility of using real-world data to fill evidentiary gaps related to antibiotic safety.

Keywords: administrative data; adverse events; antibiotics; comparative safety; urinary tract infection.

Figure 1.

A–D, Propensity score–weighted cumulative incidence curves of selected adverse drug event outcomes among patients with uncomplicated UTI, by antibiotic agent. For each outcome, the number of events by antibiotic agent is presented in Table 2. Estimates were adjusted for age, month of prescription, year of prescription, geographic region, provider specialty, alcohol or drug abuse, deficiency anemias, chronic pulmonary disease, depression, hypertension, obesity, and psychoses. Abbreviations: TMP/SMX, trimethoprim-sulfamethoxazole; UTI, urinary tract infection.

Figure 2.

A–C, Propensity score–weighted cumulative incidence curves of selected potential microbiome-related adverse event outcomes among patients with uncomplicated UTI, by antibiotic agent. For each outcome, the number of events by antibiotic agent is presented in Table 2. Estimates were adjusted for age, month of prescription, year of prescription, geographic region, provider specialty, alcohol or drug abuse, deficiency anemias, chronic pulmonary disease, depression, hypertension, obesity, and psychoses. Abbreviations: TMP/SMX, trimethoprim-sulfamethoxazole; UTI, urinary tract infection.

Figure 3.

Propensity score–weighted HR estimates of potential microbiome-related adverse events associated with antibiotic agents among patients prescribed guideline-recommended duration versus inappropriately long duration. Antibiotic duration was categorized as appropriate guideline-recommended duration (3 days for fluoroquinolones and TMP/SMX, 5 days for nitrofurantoin, 3–7 days for β-lactams) or inappropriately long duration; patients with inappropriately short duration were excluded. Propensity score weighting was implemented using standardized mortality ratio weighting wherein patients were weighted to reflect the covariate distribution in the patients who received appropriate guideline-recommended duration. Estimates were adjusted for age, month of prescription, year of prescription, geographic region, provider specialty, alcohol or drug abuse, deficiency anemias, chronic pulmonary disease, depression, hypertension, obesity, and psychoses. For HR estimation, we required 5 or more adverse event cases in both the reference antibiotic treatment group (ie, nitrofurantoin) and the comparator treatment group to ensure stability of the effect estimate. Abbreviations: CI, confidence interval; HR, hazard ratio; TMP/SMX, trimethoprim-sulfamethoxazole.