title: Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study.
abstract: BACKGROUND
  Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy.
  
  
  METHODS
  We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable.
  
  
  RESULTS
  Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29).
  
  
  CONCLUSIONS
  Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials.
  
  
  BACKGROUND
  US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.
authors.affiliation: Center for Disease Dynamics, Economics and Policy, Washington, DC, USA.
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Braykov
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Morgan
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, IA, USA.
authors.forename: Marin L
authors.initials: ML
authors.lastname: Schweizer
authors.affiliation: Infectious Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Uslan
authors.affiliation: Infectious Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Alta Bates Summit Medical Center, Oakland, CA, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Weisenberg
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Birgir
authors.initials: B
authors.lastname: Johannsson
authors.affiliation: Infectious Diseases, Denver Health Medical Center, Denver, CO, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Young
authors.affiliation: Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cantey
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, IA, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Perencevich
authors.affiliation: Clinical Services Group, HCA Inc, Nashville, TN, USA; Texas A&M Health Science Center College of Medicine, Houston, TX, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Septimus
authors.affiliation: Center for Disease Dynamics, Economics and Policy, Washington, DC, USA; Public Health Foundation of India, New Delhi, India; Princeton University, Princeton, NJ, USA. Electronic address: ramanan@cddep.org.
authors.forename: Ramanan
authors.initials: R
authors.lastname: Laxminarayan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents