Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis.
BACKGROUND
It has been axiomatic that echinocandins (e.g., caspofungin) are ineffective against mucormycosis. However, on the basis of preclinical data, we recently began treating rhino-orbital-cerebral mucormycosis (ROCM) with combination polyene-caspofungin therapy.


METHODS
To determine the impact of polyene-caspofungin therapy, ROCM cases identified by an International Classification of Diseases, Ninth Revision search were retrospectively reviewed to gather data on demographic characteristics, clinical history, and outcomes. The predefined primary end point was success (i.e., the patients was alive and not in hospice care) at 30 days after hospital discharge.


RESULTS
Forty-one patients with biopsy-proven ROCM were identified over 12 years; 23 (56%) of these patients were Hispanic, and 34 (83%) were diabetic. Patients treated with polyene-caspofungin therapy (6 evaluable patients) had superior success (100% vs. 45%; Pp.02) and Kaplan-Meier survival time (Pp.02), compared with patients treated with polyene monotherapy. Patients treated with amphotericin B lipid complex had inferior success (37% vs. 72%; Pp.03) and a higher clinical failure rate (45% vs. 21%; Pp.04), compared with patients who received other polyenes. However, patients treated with amphotericin B lipid complex plus caspofungin had superior success (100% vs. 20%; Pp.009) and survival time (Pp.01), compared with patients who received amphotericin B lipid complex alone. The benefit of combination therapy, compared with monotherapy, was most pronounced in patients with cerebral involvement (success rate, 100% vs. 25%; Pp.01). In multivariate analysis, only receipt of combination therapy was significantly associated with improved outcomes (odds ratio, 10.9; 95% confidence interval, 1.3- ;Pp.02).


CONCLUSIONS
Combination polyene-caspofungin therapy represents a promising potential alternative to polyene monotherapy for patients with ROCM. Randomized, prospective investigation of these findings is warranted.
Reed
Caitlin
C
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, University of California at Los Angeles Medical Center, Torrance, CA, USA.
Bryant
Richard
R
Ibrahim
Ashraf S
AS
Edwards
John
J
Filler
Scott G
SG
Goldberg
Robert
R
Spellberg
Brad
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D009091:Mucormycosis / Q000188:drug therapy*; D009916:Orbital Diseases / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies; D012220:Rhinitis / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000666:Amphotericin B; D000077336:Caspofungin