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.
Singh
Nina
N
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15240, USA. nis5@pitt.edu
Limaye
Ajit P
AP
Forrest
Graeme
G
Safdar
Nasia
N
Muñoz
Patricia
P
Pursell
Kenneth
K
Houston
Sally
S
Rosso
Fernando
F
Montoya
Jose G
JG
Patton
Pamela
P
Del Busto
Ramon
R
Aguado
Jose M
JM
Fisher
Robert A
RA
Klintmalm
Goran B
GB
Miller
Rachel
R
Wagener
Marilyn M
MM
Lewis
Russell E
RE
Kontoyiannis
Dimitrios P
DP
Husain
Shahid
S
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