Evaluation of FDA Boxed Warning on Prescribing Patterns of Fluoroquinolones for Uncomplicated Urinary Tract Infections.

Background: Little is known regarding the impact of the Food and Drug Administration (FDA) boxed warning on prescribing rates of fluoroquinolone (FQ) antibiotics in the outpatient setting. Objective: The primary objective of this study was to evaluate the 2016 FDA boxed warning update on FQ prescribing rates for uncomplicated urinary tract infection (uUTI). Methods: This was a single-center retrospective cohort study conducted at 6 family medicine practices, including women aged 18 to 65 years with an outpatient visit for uUTI from January 1, 2016, to December 31, 2016. Results: A total of 436 patients met inclusion. FQs were prescribed in 38% of patients before the FDA boxed warning and in 30% of patients after (8% reduction). Non-FQ prescribing had a corresponding 8% increase, comprising 62% of uUTI prescribing before the FDA boxed warning and 70% after (P = 0.08). The likelihood of being prescribed a FQ was not significantly different following release of the FDA boxed warning (adjusted odds ratio = 0.67 [95% CI = 0.41-1.10]). Variables significantly associated with an increase in FQ prescribing based on logistic regression were age ≥58 years and chronic kidney disease. Concordance of antibiotic prescribing with the Infectious Diseases Society of America clinical practice guidelines for uUTI was low, and the incidence of treatment failure was low. Conclusion and Relevance: The 2016 FDA boxed warning was not significantly associated with decreased FQ prescribing for uUTI across a large academic family medicine practice. Methods to improve education and disseminate FDA warnings in practice are needed.

ß2 -Adrenergic Receptor Gene Affects the Heart Rate Response of ß-Blockers: Evidence From 3 Clinical Studies.

ß-Blockers' heart rate (HR)-lowering effect is an important determinant of the effectiveness for this class of drugs, yet it is variable among ß-blocker-treated patients. To date, genetic studies have revealed several genetic signals associated with HR response to ß-blockers. However, these genetic signals have not been consistently replicated across multiple independent cohorts. Here we sought to use data from 3 hypertension clinical trials to validate single-nucleotide polymorphisms (SNPs) previously associated with the HR response to ß-blockers. Using linear regression analysis, we investigated the effects of 6 SNPs in 3 genes, including ADRB1, ADRB2, and GNB3, relative to the HR response following ß-blocker used in the PEAR (n = 757), PEAR-2 (n = 368), and INVEST (n = 1401) trials, adjusting for baseline HR, age, sex, and ancestry. Atenolol was used in PEAR and INVEST, and metoprolol was used in PEAR-2. We found that rs1042714 and rs1042713 in ADRB2 were significantly associated with HR response to both ß-blockers in whites (rs1042714 C-allele carriers, meta-analysis ß = -0.95 beats per minute [bpm], meta-analysis P = 3×10-4 ; rs1042713 A-allele carriers, meta-analysis ß = -1.15 bpm, meta-analysis P = 2×10-3 ). In conclusion, the results of our analyses provide strong evidence to support the hypothesis that rs1042714 and rs1042713 in the ADRB2 gene are important predictors of HR response to cardioselective ß-blockade in hypertensive patient cohorts.