Combination of Voriconazole and Caspofungin as Primary Therapy for Invasive Aspergillosis in Solid Organ Transplant Recipients: A Prospective, Multicenter, Observational Study

Baylor University, Waco, Texas, United States
Transplantation (Impact Factor: 3.83). 03/2006; 81(3):320-6. DOI: 10.1097/
Source: PubMed


: 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.
: 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.
: 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.
: 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.

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    • "It suggests that the efficacy of the combination is different between Aspergillus species and the efficacy in A. flavus and A. niger is better than in A. fumigatus. However, there are some studies of combination therapy for IPA by A. fumigatus [7, 10, 12–14], more rarely by A. flavus [15, 27] and A. niger [27, 28]. The therapeutic outcome of the studies or cases of IPA by A. flavus or A. niger are generally successful. "
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    ABSTRACT: Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high mortality. We evaluated the efficacy and compared the therapeutic effect differences of voriconazole (VRC) in combination with caspofungin (CAS) in transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger. Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1 mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day), and no drug for 10 consecutive days. The efficacy and the difference in the treatments were evaluated through prolongation of survival, reduction in serum galactomannan levels and residual fungal burden, and histological studies. For all the strains, the combination of VRC and CAS led to significant prolongation in survival (P < 0.05) and reduction in residual fungal burden (P < 0.05) compared with CAS alone, and decrease in serum galactomannan levels (P < 0.05) compared with either agent alone. The survival in the combined therapy groups was significantly improved compared to VRC monotherapy for the strains of A. flavus and A. niger (P < 0.05), but no significant difference for the strains of A. fumigatus (P > 0.05). Combination of VRC and CAS was synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA by A. fumigatus.
    Mycopathologia 12/2013; 177(1-2). DOI:10.1007/s11046-013-9719-z · 1.53 Impact Factor
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    • "Perea et al. investigated the in vitro interaction of caspofungin and voriconazole and their results indicated that a combination of caspofungin and voriconazole might be more effective against infections caused by Aspergillus spp. as compared with single treatment [20]. In a clinical trial with solid-organ transplant recipients with proven invasive aspergillosis, including liver transplant patients, Singh et al. prospectively assessed a combination therapy consisting of caspofungin and voriconazole in comparison with a historical control group which was treated with liposomal amphotericin B [21]. The overall 90-day survival rate was not different in both groups, but patients infected with Aspergillus fumigatus and patients with renal failure showed a significant better 90-day survival. "
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    ABSTRACT: Invasive aspergillosis is recognized as one of the most significant opportunistic infections after liver transplantation. Diagnosis of invasive aspergillosis in transplant recipients has been proven to be challenging, and optimal approach to the treatment of invasive aspergillosis is still controversial. We here present an unusual case of Aspergillus tracheobronchitis in the setting of liver transplantation. A 47-year-old female patient with persistent dry cough after liver transplantation developed respiratory insufficiency and was readmitted to the intensive care unit 55 days after liver transplantation. A CT scan revealed subtotal tracheal stenosis; bronchoscopy was performed, and extended white mucus coverings causative of the tracheal stenosis were removed. Microbiological assessment isolated Aspergillus fumigatus. The diagnosis was obstructive Aspergillus tracheobronchitis. The patient was started on a treatment of voriconazole 200 mg orally twice daily, adjusted to a trough level of 1-4 mg/L. For further airway management, a tracheal stent had to be implanted. The patient is alive and well 28 months after liver transplantation. Invasive aspergillosis should be considered a possible etiology in liver transplant patients presenting with unspecific symptoms such as persistent dry cough. Optimal strategies for improved and early diagnosis as well as prophylaxis need to be defined.
    07/2013; 2013:928289. DOI:10.1155/2013/928289
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    • "Until recently, there were no guidelines about the choice of antifungal therapy for Aspergillus endocarditis (Walsh et al., 2008). Data from 2 clinical trials reported that voriconazole in combination with caspofungin could improve the outcome of patients with IA (Marr et al., 2004; Singh et al., 2006). Here, the occurrence of multiple septic emboli in the brain and the impossibility of replacing the valve led us to start salvage therapy based on a combination of voriconazole and caspofungin. "
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    ABSTRACT: Aspergillus endocarditis is a rare event after heart transplantation. We report a case of Aspergillus fumigatus endocarditis after orthotopic heart transplantation. The patient was treated with a combination of voriconazole and caspofungin without valve replacement and survived for 168 days after the diagnosis. Previously reported cases are reviewed.
    Diagnostic Microbiology and Infectious Disease 01/2009; 62(4):453-6. DOI:10.1016/j.diagmicrobio.2008.08.007 · 2.46 Impact Factor
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