title: In vitro activity and pharmacodynamics of commonly used antibiotics against adult systemic isolates of Escherichia coli and Pseudomonas aeruginosa at Forty US Hospitals.
abstract: BACKGROUND
  Treatment of infections caused by gram-negative bacilli is increasingly challenging because of emerging resistance. Current surveillance data are informative, but may not discern differences by infection site and clinical setting, and do not incorporate pharmacodynamic (PD) characteristics when determining susceptibility.
  
  
  OBJECTIVE
  This study explored the differences in infection site and clinical setting and evaluated dose-optimization strategies using PD principles. The stud focused only on systemic isolates, and targeted a cohort of 40 hospitals in the United States with a nationwide geographic distribution.
  
  
  METHODS
  Nonduplicate, nonurine isolates of Escherichia coli (n = 937) and Pseudomonas aeruginosa (n = 1044) collected from adult patients at 40 US hospitals underwent MIC testing by broth microdilution to 15 agents. Results were analyzed by infection site and unit type (ward or intensive care unit [ICU]). PD modeling employing Monte Carlo simulation was used to predict the microbiologic success of varying dosing strategies.
  
  
  RESULTS
  E coli were highly susceptible except to fluoroquinolones; 6.8% were multidrug resistant (MDR) and were more likely in ICUs (risk ratio [RR], 2.5; 95% CI, 1.6-4.0). P aeruginosa displayed <or=86% susceptibility for all agents; MICs differed significantly by site of infection (P < 0.05). Isolates were 9.2%MDR (less likely in wound infections [RR, 0.5; 95% CI, 0.3-0.9]). PD simulations predicted results similar to breakpoint-derived susceptibilities for both species, with notable exceptions of piperacillin/tazobactam and fluoroquinolones, which underpredicted susceptibility by as much as 20%. Prolonged (3 hours) or continuous infusion regimens of beta-lactams appeared to improve drug exposure.
  
  
  CONCLUSIONS
  These data suggest that susceptibility of E coli to commonly used antibiotics remains high (>90% for most drug classes), with the important exception of the fluoroquinolones; however, susceptibility of P aeruginosa is low enough to warrant concern. Attention to the source of the organism and the patient's location in an ICU or a ward-combined with knowledge of local epidemiology and PD principles--should prove valuable in empiric agent selection. Additionally, reassessment of breakpoints employing PD principles is recommended, particularly for fluoroquinolones and piperacillin/tazobactam.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Eagye
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.forename: Christina A
authors.initials: CA
authors.lastname: Sutherland
authors.forename: Henry
authors.initials: H
authors.lastname: Christensen
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003428:Cross Infection / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014481:United States / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents