Caspofungin as first-line therapy for the treatment of invasive aspergillosis after thoracic organ transplantation.
BACKGROUND
Although amphotericin was the gold standard in the treatment of invasive aspergillosis in transplant recipients, nephrotoxicity and lack of efficacy often limits its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressant trough levels significantly. We report our first clinical experience with the use of caspofungin as first-line therapy in heart and lung transplant recipients with invasive aspergillosis.


METHODS
Caspofungin was administered at 50 to 70 mg/day in heart and lung transplant recipients with renal impairment while invasive aspergillosis was diagnosed and classified. Aspergillus serology, serologic inflammatory markers, and X-rays were taken to monitor infectious activity. Creatinine and immunosuppressant trough levels were monitored closely.


RESULTS
Invasive aspergillosis was diagnosed by chest X-ray, serology, and positive sputum in 1 heart-lung, 7 heart, and 4 single-lung transplant recipients, and caspofungin was administered for a mean time of 21 +/- 9 days. Basic immunosuppressants were tacrolimus in 9 patients or cyclosporine in 3. Complete remission was achieved in 10 patients (83%). Adverse effects of caspofungin were fever in 6, diarrhea in 3, and neutropenia in 1. Renal function remained stable (3.2 +/- 1 mg/dl before vs 2.3 +/- 0.9 mg/dl after, p = 0.07). Trough levels of all immunosuppressants did not change significantly during caspofungin treatment (10.9 +/- 4.1 ng/ml before vs 9.9 +/- 4.0 ng/ml after [p = 0.31] for tacrolimus; 214 +/- 98 ng/ml before vs 229 +/- 88 ng/ml after [p = 0.41] for cyclosporin A), while the administered dosage remained stable.


CONCLUSIONS
In heart and lung transplant recipients with invasive aspergillosis, caspofungin seemed to be an effective anti-fungal agent with a promising safety profile. Further prospective randomized trials are needed to investigate an advantageous role of caspofungin in the treatment of invasive aspergillosis.
Groetzner
Jan
J
Department of Cardio-Thoracic Surgery, Cologne University Hospital, Cologne, Germany. jgroetzner@t-online.de
Kaczmarek
Ingo
I
Wittwer
Thorsten
T
Strauch
Justus
J
Meiser
Bruno
B
Wahlers
Thorsten
T
Daebritz
Sabine
S
Reichart
Bruno
B
D000908:Antibodies, Fungal / Q000032:analysis; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D001230:Aspergillus / Q000276:immunology / Q000302:isolation & purification; D000077336:Caspofungin; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D055666:Lipopeptides; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011446:Prospective Studies; D016896:Treatment Outcome
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D000077336:Caspofungin