PURPOSE: Inappropriate empiric treatment of ventilator-associated pneumonia (VAP) increases mortality. Pseudomonas aeruginosa (PA), the cause of ¼ of all VAP, is increasingly resistant to conventional antibiotics. The rates of PA-VAP susceptibility to doripenem (DOR) (81.5%) are higher than to imipenem (IMI) (74.1%). While 7.8% of isolates resistant to IMI are sensitive to DOR (DOR-S), only 0.4% of DOR-resistant PA is sensitive to IMI (IMI-S). We developed a model to quantify outcome differences between strategies of empiric treatment of VAP with DOR vs. IMI.
METHODS: We designed a decision model in a hypothetical 1,000-patient cohort with VAP treated empirically with either DOR or IMI. We examined the differences in the number of deaths, hospital LOS and total costs in the cohort 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 PA VAP attributable mortality of 0.384 and a 49% relative risk reduction in mortality in PA sensitive to empiric drug compared to a resistant one, total cost savings associated with DOR were $362,101 per 1,000 patients treated. Additionally, 117.4 days of hospitalization and 3 deaths were avoided. The estimates were most sensitive to the proportion isolates DOR-S and IMI-S and to per-case hospital costs. In a multivariable analysis, cost savings persisted across >80% of the trials (95% confidence interval -$347,335 to $1,789,786).
CONCLUSION: Given the current sensitivity profile of PA to DOR and IMI, the strategy of empiric treatment of VAP with DOR may dominate that with IMI by being both life- and cost-saving.
CLINICAL IMPLICATIONS: Depending on the local susceptibility patterns, DOR may be a better choice of empiric therapy for VAP.Brown NP et al. Crit Care Med 2008:Crouch Brewer S et al. Chest 1996:109;1019–29Lautenbach E et al. Infect Control Hosp Epidemiol 2006:27:893–900.
DISCLOSURE: Marya Zilberberg, None.