Invasive fungal infections and antifungal therapies in solid organ transplant recipients

Gabardi, Steven; Kubiak, David W.; Chandraker, Anil; Tullius, Stefan G.

doi:10.1111/j.1432-2277.2007.00511.x

Cited by 60 publications

(46 citation statements)

References 159 publications

(315 reference statements)

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“…Nevertheless, 10 mg/kg VCZ positive control was significantly more effective at decreasing the fungal burden than HME-ITZ formulations. This is likely explained by the higher efficacy of VCZ specifically against Aspergillus fumigatus [58]. Indeed, VCZ is the reference treatment against Aspergillus fumigatus [40], and this justifies the selection of VCZ as the reference treatment allowing the HME-ITZ formulation to be challenged.…”

Section: Discussionmentioning

confidence: 99%

Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection

Maincent

Najvar

Kirkpatrick

et al. 2016

Drug Development and Industrial Pharmacy

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Previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a pH dependent enteric polymer combined with hydrophilic additives (HME-ITZ), exhibited improved in vitro dissolution properties. These properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (ITZ) systemic levels. The objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and efficacy of this orally administered modified release ITZ dosage form against invasive Aspergillus fumigatus. A mouse and guinea pig model were investigated and compared to results previously published. In the mouse model, despite similar levels as previously reported values, plasma and lung levels were variable and fungal burden was not statistically different for placebo controls, HME-ITZ and Sporanox ® (ITZ oral solution). This study demonstrated that the mouse model is a poor choice for studying modified release ITZ dosage forms based on pH dependent enteric polymers due to low fluid volume available for dissolution and low intestinal pH. To the contrary, guinea pig was a suitable model to evaluate modified release ITZ dosage forms. Indeed, a significant decrease in lung fungal burden as a result of high and sustained ITZ tissue levels was measured. Sufficiently high intestinal pH and fluids available for dissolution likely facilitated the dissolution process. Despite high ITZ tissue level, the primary therapeutic agent voriconazole exhibited an even more pronounced decrease in fungal burden due to its reported higher clinical efficacy specifically against Aspergillus fumigatus.

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Section: Discussionmentioning

confidence: 99%

Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection

Maincent

Najvar

Kirkpatrick

et al. 2016

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

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“…Aspergillus spp. have been isolated from approximately 9%–34% of patients with invasive fungal infection after liver transplantation [1, 5]. Risk factors for invasive aspergillosis in liver transplant recipients include pretransplant hepatic failure, primary graft dysfunction or nonfunction, retransplantation, dialysis treatment, and high transfusion requirement [6].…”

Section: Discussionmentioning

confidence: 99%

“…Invasive aspergillosis is one of the most significant opportunistic infections in solid-organ transplant recipients, and its diagnosis carries a high mortality rate [1]. Early diagnosis of invasive aspergillosis has been proven to be challenging, and the optimal approach to the treatment of invasive aspergillosis is still controversial.…”

Section: Introductionmentioning

confidence: 99%

AspergillusTracheobronchitis Causing Subtotal Tracheal Stenosis in a Liver Transplant Recipient

Radünz

Kirchner²,

Treckmann³

et al. 2013

Case Reports in Transplantation

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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.

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“…The prevalence of invasive fungal infections has decreased over the last decade, due, in a large part, to improvements in transplant surgical methods [10]. Invasive fungal infections following kidney transplantation are rare, occurring in only 1-14 % of kidney transplants [11]. Candida spp.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus and Aspergillus spp. coinfection in organ transplantation: a case report and review of the literature

et al. 2012

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With the advent of potent immunosuppressive options, acute rejection episodes have decreased at the expense of increased incidence of opportunistic infections in solid organ recipients. In the absence of any preventive therapy, 30-75 % of transplant recipients develop cytomegalovirus (CMV) infection. Candida spp. and Aspergillus spp. account for more than 80 % of invasive fungal infections in solid organ recipients. This co-occurrence of two commonly seen opportunistic infections may end up in fatality. Here, we present a case of concomitant Aspergillus spp. and CMV infection and discuss the relevant literature. A 54-year-old male patient presented with fever, shortness of breath, and chest pain on the 9th posttransplant week after renal transplantation. CMV-DNA by polymerase chain reaction (PCR) was 1,680,000 copies/ml, thus, valganciclovir dose was increased. There were inspiratory crackles at both lung bases, and chest computed tomography (CT) revealed multiple fungal balls throughout the right lung. Galactomannan antigen was positive, and voriconazole and other antimicrobials were subsequently added to the treatment. At the end of the therapy, on control CT, pneumonic consolidation had disappeared, sputum cultures didn't show Aspergillus spp., and CMV-DNA reduced to 700 copies/ml. The patient showed a favorable clinical response to combined treatment; fever, dyspnea, and pleuritic chest pain disappeared. Both CMV disease and aspergillosis may present as pulmonary disease; thus, the characterization of one may not preclude the search for the other and the timely initiation of treatment is of paramount importance for good outcomes.

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Invasive fungal infections and antifungal therapies in solid organ transplant recipients

Cited by 60 publications

References 159 publications

Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection

Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection

AspergillusTracheobronchitis Causing Subtotal Tracheal Stenosis in a Liver Transplant Recipient

Cytomegalovirus and Aspergillus spp. coinfection in organ transplantation: a case report and review of the literature

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