A targeted peritransplant antifungal strategy for the prevention of invasive fungal disease after lung transplantation:  a sequential cohort analysis.
BACKGROUND
Lung transplant recipients are at high risk of invasive fungal disease (IFD), particularly invasive aspergillosis and candidiasis. The antifungal strategy that optimally balances effective reduction of IFD with a minimum of toxicity remains undefined; universal triazole prophylaxis is common at lung transplantation (LT) centers, despite the well-known toxicities and costs of this approach.


METHODS
We implemented an antifungal strategy in March 2007 targeted at LT recipients at highest risk for IFD based on our institutional epidemiology. All patients received inhaled amphotericin B during their initial LT hospitalization, bilateral lung transplant recipients received 7 to 10 days of micafungin, and only patients with growth of yeast or mold in their day-of-transplant cultures received further oral antifungal therapy tailored to their fungal isolate.


RESULTS
IFD events were assessed in sequential cohorts composed of 82 lung transplant recipients before and 83 patients after the implementation of this targeted antifungal strategy. We observed a sharp decline in IFD; in the second cohort, 87%, 91%, and 96% of patients were free of IFD, invasive candidiasis, and invasive aspergillosis at 1 year. Only 19% of patients in the second cohort received systemic antifungal therapy beyond the initial LT hospitalization, and no patients experienced antifungal drug-related toxicity or IFD-associated mortality.


CONCLUSIONS
The targeted antifungal strategy studied seems to be a reasonable approach to reducing post-LT IFD events while limiting treatment-related toxicities and costs.
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. skoo@partners.org
Sophia
S
Koo
David W
DW
Kubiak
Nicolas C
NC
Issa
Amanda
A
Dietzek
Steve
S
Boukedes
Phillip C
PC
Camp
Hilary J
HJ
Goldberg
Lindsey R
LR
Baden
Anne L
AL
Fuhlbrigge
Francisco M
FM
Marty
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control; D002177:Candidiasis / Q000209:etiology / Q000517:prevention & control; D015331:Cohort Studies; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000627:therapeutic use; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology* / Q000517:prevention & control*; D012306:Risk; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D000666:Amphotericin B; D000077551:Micafungin