Treatment failure in invasive aspergillosis: susceptibility of deep tissue isolates following treatment with amphotericin B

Paterson, Pamela; Seaton, Shila; Prentice, H. G.; Kibbler, C C

doi:10.1093/jac/dkg434

Cited by 59 publications

(46 citation statements)

References 9 publications

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“…However, clinical failure in invasive aspergillosis may have many causes other than drug resistance; furthermore, in patients who have died from inva-sive aspergillosis despite amphotericin treatment, emergence of resistance to amphotericin or itraconazole during treatment has not been detected (65,207). In a review of 11 patients with hematologic malignancies in whom A. fumigatus or A. flavus was isolated, while on amphotericin, resistance to amphotericin was not detected, but it was thought that poor drug penetration to the site of infection may have been a contributor to failure (238).…”

Section: Management In Vitro Susceptibility To Antifungal Agentsmentioning

confidence: 99%

AspergillusInfections in Transplant Recipients

2005

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Aspergillus infections are occurring with an increasing frequency in transplant recipients. Notable changes in the epidemiologic characteristics of this infection have occurred; these include a change in risk factors and later onset of infection. Management of invasive aspergillosis continues to be challenging, and the mortality rate, despite the use of newer antifungal agents, remains unacceptably high. Performing molecular studies to discern new targets for antifungal activity, identifying signaling pathways that may be amenable to immunologic interventions, assessing combination regimens of antifungal agents or combining antifungal agents with modulation of the host defense mechanisms, and devising diagnostic assays that can rapidly and reliably diagnose infections represent areas for future investigations that may lead to further improvement in outcomes

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Section: Management In Vitro Susceptibility To Antifungal Agentsmentioning

confidence: 99%

AspergillusInfections in Transplant Recipients

2005

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“…A. fumigatus is usually highly susceptible to amphotericin B in vitro, with a MIC of Ͻ1 g/ml. For A. fumigatus and A. flavus, failure of amphotericin B may be related to poor drug penetration as well as decreased MIC for some isolates (16). Resistance to itraconazole is uncommon but is associated with clinical failure and failure in animal models (6,24).…”

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confidence: 99%

Antifungal Therapy of Murine Aspergillus terreus Infection

Graybill

Hernandez

Bocanegra

et al. 2004

Antimicrob Agents Chemother

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“…Liposomal amphotericin B (32,33) and voriconazole (34-36) are common drugs in prophylactic use to prevent fungal infections in high-risk patients, although treatment failure and breakthrough of invasive fungal infections have been observed (2,37,38). Furthermore, echinocandins generally show good in vitro effectiveness against Candida and Aspergillus species, and several retrospective studies on the efficacies of micafungin and caspofungin in prophylactic and therapeutic approaches showed similar efficacies to those observed for various azoles and amphotericin B (39).…”

Section: Discussionmentioning

confidence: 99%

“…A review of 595 patients with proven or probable invasive aspergillosis identified a high rate of treatment failure for a wide range of antifungal drugs (36%), with only 27% of treated patients demonstrating a complete response to treatment (1). While in some cases failure of treatment may result from low susceptibility of the pathogen to the respective antifungal, restricted delivery to the site of infection may be another reason for a limited treatment response (2). Therefore, practice guidelines addressing treatment choices support the aggressive use of different drugs, including amphotericin B and its lipid formulation as well as different azoles, including itraconazole, voriconazole, and posaconazole, at the highest recommended doses (3).…”

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Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

Galiger

Brock

Jouvion

et al. 2013

Antimicrob Agents Chemother

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c Aspergillus fumigatus causes life-threatening infections, especially in immunocompromised patients. Common drugs for therapy of aspergillosis are polyenes, azoles, and echinocandins. However, despite in vitro efficacy of these antifungals, treatment failure is frequently observed. In this study, we established bioluminescence imaging to monitor drug efficacy under in vitro and in vivo conditions. In vitro assays confirmed the effectiveness of liposomal amphotericin B, voriconazole, and anidulafungin. Liposomal amphotericin B and voriconazole were fungicidal, whereas anidulafungin allowed initial germination of conidia that stopped elongation but allowed the conidia to remain viable. In vivo studies were performed with a leukopenic murine model. Mice were challenged by intranasal instillation with a bioluminescent reporter strain (5 ؋ 10 5 and 2.5 ؋ 10 5 conidia), and therapy efficacies of liposomal amphotericin B, voriconazole, and anidulafungin were monitored. For monotherapy, the highest treatment efficacy was observed with liposomal amphotericin B, whereas the efficacies of voriconazole and anidulafungin were strongly dependent on the infectious dose. When therapy efficacy was studied with different drug combinations, all combinations improved the rate of treatment success compared to that with monotherapy. One hundred percent survival was obtained for treatment with a combination of liposomal amphotericin B and anidulafungin, which prevented not only pulmonary infections but also infections of the sinus. In conclusion, combination therapy increases treatment success, at least in the murine infection model. In addition, our novel approach based on real-time imaging enables in vivo monitoring of drug efficacy in different organs during therapy of invasive aspergillosis.

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Treatment failure in invasive aspergillosis: susceptibility of deep tissue isolates following treatment with amphotericin B

Cited by 59 publications

References 9 publications

AspergillusInfections in Transplant Recipients

AspergillusInfections in Transplant Recipients

Antifungal Therapy of Murine Aspergillus terreus Infection

Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

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