664. Impact of Area-Under-the- Concentration Curve (AUIC) and Intravenous (IV) Catheter Removal On Eradication Rates of Candidemia with Micafungin (M) and Caspofungin (C)
Session: Abstracts: Mycology
Friday, October 22, 2010
C. Rotstein,  J. Schentag, P. Pappas, B. Footer: University of Toronto, Toronto, Canada; CPL  Associates  and SUNY-Buffalo, Buffalo, NY; and University of Alabama at Birmingham, Birmingham, AL.

Background: The clinical trial comparing M at 2 different doses (100 and 150 mg) IV daily to C IV daily demonstrated the noninferiority of M at the primary endpoint with no differences in the eradication rates of Candida from the bloodstream between the drugs. However, the results call into question the rationale of why M 150 produced a slightly lower success rate and slower time to eradication of Candida from the bloodstream than M 100 (median time 3 versus 2 days) possibly influenced by the less frequent removal of IV catheters with M 150 (73.4% vs. 83.3%). These observations may be explained by the pharmacodynamic properties of M 100 relative to M 150 and C. We therefore explored whether AUIC could explain these differences.

Methods: Patient data from the clinical trial were used to generate AUIC curves. Individual patient serum concentrations were extrapolated from previously published pharmacokinetic data. AUICs were calculated based on calculated individual creatinine clearances and minimum inhibitory concentrations of the Candida isolates causing bloodstream infections in the trial. Pathogen eradication and catheter removal were derived from the published clinical trial.

Results: M 100 and M 150 patients possessing AUICs <400 and C patients with AUICs <100 demonstrated slower eradication than those with AUICs ≥400 (M 100 n=82, M 150 n=86) or ≥100 (C patients n=130). For both M 100 and M 150 with AUICs ≥400 IV catheter removal did not produce faster eradication rates than those patients who did not undergo IV catheter removal (p=.58 and p=.24). However, for C patients with AUICs ≥100 removal of IV catheters showed a trend toward faster eradication (p=.07).

Conclusion: For M, if AUIC values ≥400 were achieved, catheter removal did not influence eradication of Candida from the bloodstream, whereas with C a difference was noted. Thus with M, provided that optimal dosing of an echinocandin is given, catheter removal does not influence success.


Subject Category: A. Antimicrobial agents and Resistance

Speakers:
Coleman Rotstein, MD , Transplant Infectious Diseases, University of Toronto, Toronto, ON, Canada

Disclosures:

C. Rotstein, Yes
Astellas : Investigator and Speaker's Bureau, Research grant and Speaker honorarium
Pfizer: Investigator and Speaker's Bureau, Research grant and Speaker honorarium
Merck : Investigator and Speaker's Bureau, Research grant and Speaker honorarium

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