Purpose: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects. Methods: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects were interviewed using a semi-structured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs. Results: Key barriers included: (1) limitations in integrating genomic data and clinical decision support tools into electronic health records; (2) physician reluctance towards genomic research participation and clinical implementation due to a limited evidence base; (3) inadequate reimbursement for genomic medicine; (4) communication among and between investigators and clinicians; (5) lack of clinical and leadership engagement. Conclusion: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice.

BackgroundAcinetobacter baumannii can cause serious healthcare-associated infections (HAIs) and the incidence is increasing, with many strains now resistant to multiple antibiotic classes. The aims of this study were to examine factors associated with HAIs caused by antimicrobial-resistant as compared with antimicrobial-susceptible strains of A. baumannii and to investigate trends in the incidence of resistance over time. Electronic data from two U.S. hospitals in a large urban healthcare system in over the years 2006–2012 were used for the analysis. Multiple logistic regression was used to explore risk factors for infection with A. baumannii resistant to ampicillin or ampicillin/sulbactam in the bloodstream, urinary tract, and respiratory tract. The Cochran-Armitage trend test was used to explore resistance trends over time.FindingsA total of 671 adults with first-time A. baumannii infection were included in the analysis; 302 isolates (45 %) were resistant to ampicillin or ampicillin/sulbactam and 369 (55 %) were susceptible. In the multivariable analysis, significant risk factors included longer length of stay prior to infection (Odds Ratio [OR] = 1.03; 95 % Confidence Interval [CI]: 1.01, 1.04), hospital A versus B (OR = 0.35; 95 % CI: 0.13, 0.93), and antibiotic use prior to infection (OR = 2.88; 95 % CI: 1.02, 8.13). Resistance was more common in respiratory infections (OR = 2.96; 95 % CI: 1.04, 8.44). No trend was found between year of infection and resistance.ConclusionsThe risk factors we identified are consistent with previous findings, but we found no evidence in this population that resistance to ampicillin or ampicillin/sulbactam was increasing over time.

Echinocandins are used for treatment of invasive candidiasis, but data on their use in children are limited. We sought to describe the epidemiology of echinocandin use in hospitalized children in the United States.We performed a retrospective cohort study of children <18 years of age hospitalized between January 2005 and December 2015 and exposed to ≥1 day of a systemic antifungal agent using the Pediatric Health Information System (PHIS) database. Univariate analyses compared recipients of two echinocandin agents, caspofungin and micafungin. Crude prescribing rates of each antifungal group were calculated across hospitals and per year. The rate of antifungal agent prescribing over time was assessed using two-level mixed-effects negative binomial regression, accounting for variability in prescribing by hospital over time. From 2005 to 2015, fluconazole was prescribed most often (n = 148,859, 74.3%), followed by mould-active triazoles (n = 36,131, 18.0%), amphotericin products (n = 29,008, 14.5%), and echinocandins (n = 28,371, 14.2%). The crude rate of systemic antifungal prescribing decreased across all PHIS hospitals from 36.3 to 33.8 per 1000 admissions during the study period, but echinocandin prescribing increased from 2.2 to 7.2 per 1000 admissions. A mixed effects regression model revealed that echinocandin prescribing increased by 15.1% per year (95% CI 11.2-19.2). Echinocandin administration increased from 6.1% to 21.0% of admissions during which a systemic antifungal agent was given. In conclusion, echinocandin use has increased significantly over time, accounting for an increasing proportion of systemic antifungal prescribing in children.

Background: Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones.Purpose: To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction.Methods: We conducted a propensity score-matched inception cohort study using claims data from a commercially insured population. Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use.Results: Our cohort contained 976 568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference <0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05-1.11) for CNS dysfunction, and 1.09 (95% CI 1.07-1.11) for the most commonly occurring PNS dysfunction outcome.Conclusions: Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population.