Standard versus prolonged doripenem infusion for treatment of gram-negative infections

BACKGROUND: Doripenem is the most recently introduced carbapenem, with a broad spectrum of antimicrobial activity. Preliminary data indicated that activity is optimized by maximizing the time that serum concentration remains above the minimum inhibitory concentration; however, limited clinical data are available to support this approach. OBJECTIVE: To compare clinical outcomes before and after implementation of a hospital-wide initiative extending the duration of infusion for doripenem from 1 hour (standard) to 4 hours (prolonged). METHODS: This retrospective, quasi-experimental study compared clinical outcomes associated with doripenem administered as a 1-hour infusion versus a 4-hour infusion for treatment of suspected or documented infections caused by gram-negative organisms. Outcomes were assessed for the entire cohort, as well as for the subpopulation of patients admitted to the intensive care unit. RESULTS: Two hundred patients were included; 106 patients received doripenem via standard infusion and 94 patients via prolonged infusion. No significant differences were noted between the treatment groups in clinical success, length of stay, or duration of treatment when the entire cohort was evaluated. In the critically ill subgroup, pneumonia, standard-infusion doripenem, and concomitant bacteremia were independent predictors of clinical failure (adjusted odds ratio [95% CI] 7.8 [2.4- 25.6], 5.5 [1.6-18.7], and 7.0 [1.6-31.3], respectively). Additionally, critically ill patients who received doripenem via standard infusion were significantly more likely to experience recurrence of infection or death within 90 days. No significant differences were noted in length of stay or duration of bacteremia. CONCLUSIONS: The duration of infusion did not significantly impact outcomes when the entire cohort was compared; however, prolonged infusion of doripenem was associated with significantly improved clinical outcomes among critically ill patients. These findings support the use of prolonged infusion of doripenem for critically ill patients.