Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.
BACKGROUND
: The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined.


METHODS
: Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome.


RESULTS
: Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome.


CONCLUSIONS
: Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15240, USA. nis5@pitt.edu
Nina
N
Singh
Ajit P
AP
Limaye
Graeme
G
Forrest
Nasia
N
Safdar
Patricia
P
Muñoz
Kenneth
K
Pursell
Sally
S
Houston
Fernando
F
Rosso
Jose G
JG
Montoya
Pamela
P
Patton
Ramon
R
Del Busto
Jose M
JM
Aguado
Robert A
RA
Fisher
Goran B
GB
Klintmalm
Rachel
R
Miller
Marilyn M
MM
Wagener
Russell E
RE
Lewis
Dimitrios P
DP
Kontoyiannis
Shahid
S
Husain
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000302:isolation & purification; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000401:mortality*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000077336:Caspofungin; D065819:Voriconazole