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Published on: September 9, 2015
Standard versus prolonged doripenem infusion for treatment of gram-negative infections
Lama Hsaiky1, Kyle P Murray, Lianne Kokoska
1Department of Pharmacy, Oakwood Hospital and Medical Center, Dearborn, MI, USA. lama.hsaiky@oakwood.org
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.
Insights
Prolonged doripenem infusions (4 hours) improved outcomes in critically ill patients compared to standard 1-hour infusions. This strategy may enhance treatment effectiveness for severe gram-negative infections in intensive care units.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Doripenem, a broad-spectrum carbapenem, has optimized activity when serum concentrations exceed the minimum inhibitory concentration.
- Limited clinical data exist to support optimizing doripenem administration by maximizing time above the minimum inhibitory concentration.
Purpose of the Study:
- To evaluate the impact of extending doripenem infusion duration from 1 hour to 4 hours on clinical outcomes.
- To compare outcomes in all patients and a subgroup of critically ill patients receiving doripenem.
Main Methods:
- Retrospective, quasi-experimental study design.
- Comparison of clinical outcomes for doripenem administered via 1-hour (standard) versus 4-hour (prolonged) infusions.
- Inclusion of both general patient cohort and intensive care unit (ICU) subpopulation.
Main Results:
- No significant differences in clinical success, length of stay, or treatment duration for the overall cohort.
- In critically ill patients, prolonged infusion was associated with improved outcomes.
- Pneumonia, standard-infusion doripenem, and bacteremia predicted clinical failure in critically ill patients.
Conclusions:
- Extending doripenem infusion duration to 4 hours did not impact outcomes in the general patient population.
- Prolonged doripenem infusion significantly improved clinical outcomes in critically ill patients.
- Findings support the use of prolonged doripenem infusions for critically ill patients.
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