title: Cost-effectiveness model of empiric doripenem compared with imipenem-cilastatin in ventilator-associated pneumonia.
abstract: BACKGROUND
  Ventilator-associated pneumonia (VAP) is a common complication of critical illness among surgical and trauma patients. Inappropriate empiric treatment of VAP increases the mortality rate. The rates of Pseudomonas aeruginosa (PA) VAP susceptibility to doripenem (DOR) are higher than those to imipenem-cilastatin (IMI). We developed a model to quantify outcome differences between strategies of empiric treatment of VAP with DOR vs. IMI.
  
  
  METHODS
  We designed a cost-effectiveness model comparing empiric treatment of VAP with DOR vs. IMI from both the hospital and societal perspectives. We examined the differences in the number of deaths, hospital length of stay (LOS), total costs, and quality-adjusted life years (QALY) under each scenario and conducted Monte Carlo simulations and sensitivity analyses to determine the stability of our estimates. Drug costs were taken as 80% of wholesale acquisition costs, with other inputs derived from the literature.
  
  
  RESULTS
  In the base case analysis, assuming a PA-VAP attributable mortality rate of 38.4% and a 49% relative risk reduction in deaths in PA-sensitive (PA-S) infections to empiric drug compared with a resistant PA (PA-R) organism, DOR use resulted in three additional deaths avoided, 117.4 days of hospitalization averted, and hospital savings of $422,524 per 1,000 patients treated at a cost of $5,748/QALY. All estimates were most sensitive to the costs of treating PA-S and PA-R infections. In a multivariable analysis, hospital cost savings persisted across >80% of the simulations (95% confidence interval $432,615-$2,148,540).
  
  
  CONCLUSIONS
  Given the current microbiologic sensitivity profile of PA to DOR and IMI, and depending on the local susceptibility patterns and in institutions where DOR in vitro susceptibilities are superior to those of other carbapenems for PA clinical isolates, empiric treatment of VAP with DOR may dominate that with IMI by being both life- and cost-saving.
authors.affiliation: School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA. Marya@evimedgroup.org
authors.forename: Marya D
authors.initials: MD
authors.lastname: Zilberberg
authors.forename: Samir H
authors.initials: SH
authors.lastname: Mody
authors.forename: Joyce
authors.initials: J
authors.lastname: Chen
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shorr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000191:economics*; D015780:Carbapenems / Q000008:administration & dosage* / Q000191:economics*; D015377:Cilastatin / Q000008:administration & dosage* / Q000191:economics*; D000077728:Cilastatin, Imipenem Drug Combination; D003362:Cost-Benefit Analysis; D000077726:Doripenem; D004338:Drug Combinations; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000191:economics*; D007902:Length of Stay / Q000191:economics / Q000706:statistics & numerical data; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000401:mortality; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D019057:Quality-Adjusted Life Years; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077726:Doripenem