EDTA as an adjunct antifungal agent for invasive pulmonary aspergillosis in a rodent model.
Rats immunosuppressed by the administration of cyclophosphamide and cortisone acetate and then infected with Aspergillus fumigatus were treated with an antifungal drug, EDTA, or a combination of one of the antifungal agents, amphotericin B lipid complex (ABLC; 5 mg/kg of body weight/day for 7 days), and EDTA (30 mg/kg/day for 7 days). The mortality rate was reduced, the duration of survival was increased, fewer A. fumigatus organisms were recovered from the lungs, and less-severe lung lesions were seen histopathologically in the rats receiving the combination treatment than in the rats receiving either an antifungal agent or EDTA alone. Further studies regarding the mechanisms of EDTA and its interactions with ABLC are warranted, and further studies are needed to more fully examine the safety, tolerance, and optimal dosing of EDTA in the treatment of this and other fungal infections.
Hachem
Ray
R
Department of Infectious Diseases, Infection Control and Employee Health, Unit 402, The University of Texas M. D. Anderson Cancer Center, P.O. Box 301402, Houston, TX 77030-1402, USA. rhachem@mdanderson.org
Bahna
Paul
P
Hanna
Hend
H
Stephens
L Clifton
LC
Raad
Issam
I
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D002118:Calcium / Q000032:analysis; D015169:Colony Count, Microbial; D016001:Confidence Intervals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004492:Edetic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D013997:Time Factors
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B; D004492:Edetic Acid; D003404:Creatinine; D002118:Calcium