Combination antifungal therapy: what can and should we expect?

Johnson, Melissa D.; Perfect, John R.

doi:10.1038/sj.bmt.1705687

Cited by 33 publications

(19 citation statements)

References 66 publications

(69 reference statements)

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“…Invasive mucormycosis and scedosporiosis are unusual and highly lethal IFIs that can arise in the postengraftment period of HSCT. Isolated, they can achieve a mortality rate superior to 90% in this kind of patients [9, 10]. To our knowledge, there have been few reports of these two IFIs arising in the same patient [11, 12].…”

Section: Discussionmentioning

confidence: 99%

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RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

Marques

Vaz

Branca

et al. 2011

Case Reports in Medicine

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Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

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Section: Discussionmentioning

confidence: 99%

“…Dosage of 800 mg/day in divided doses has been reported [5]. There are also case reports that describe successful outcomes with combination of liposomal amphotericin B with either caspofungin or posaconazole where single-agent therapy has failed [5, 6, 9]. Caspofungin monotherapy has no in vitro activity against Mucorales.…”

Section: Discussionmentioning

confidence: 99%

RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

Marques

Vaz

Branca

et al. 2011

Case Reports in Medicine

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“…Numerous authors have published reviews addressing the use of combination antifungal therapy for infections such as candidiasis, aspergillosis, and cryptococcosis [46][47][48][49][50][51]. Potential advantages of combination antifungal therapy include increased antimicrobial activity that allows for greater microbial killing, less drug resistance, expanded spectrum of activity, enhanced tissue distribution with the use of two agents, and minimization of dose-related toxicities.…”

Section: Combination Antifungal Treatmentmentioning

confidence: 98%

An update on the pharmacoeconomics of antifungal pharmacotherapy

Wieczorkiewicz

Jourjy

Danziger

2009

Curr Fungal Infect Rep

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“…Combination therapy holds the promise to increase efficacy and enhance fungal killing of antifungal agents. The introduction of new antifungal compounds with different mechanisms of action has made antifungal combination therapy feasible 1,2 . Antifungal agents target specific cell targets, such as cell‐membrane integrity (polyenes), ergosterol biosynthesis (triazoles) and cell‐wall integrity (echinocandins).…”

Section: Introductionmentioning

confidence: 99%

“…Combination therapy with two or more agents may improve clinical outcome of this devastating infection 1,2 . Previous in vitro studies of double combination therapy with triazoles + echinocandins against invasive aspergillosis have shown additive or synergistic interaction 3–6 .…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacodynamic interaction analysis of triple combinations of caspofungin and voriconazole or ravuconazole with subinhibitory concentrations of amphotericin B againstAspergillusspp.

Demchok

Meletiadis

Roilides

et al. 2010

Mycoses

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Triple combination therapy with an antifungal triazole, echinocandin and amphotericin B (AmB) is used in some centres to treat refractory aspergillosis. The objective of this study was to investigate the effect of subinhibitory concentrations of AmB on the double combinations of caspofungin (CAS) + voriconazole (VOR) or ravuconazole (RAV) against Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Isolates were studied in triplicate against CAS/VOR and CAS/RAV combinations by chequerboard broth microdilution. AmB was added to each double combination at concentrations of 0, 0.1 and 0.2 microg ml(-1). The fractional inhibitory concentration (FIC) index was calculated for the double and triple combinations. Comparative analysis was performed by repeated measures analysis followed by Dunnett's post-test. The double combinations of CAS/RAV and CAS/VOR were synergistic or additive in most conditions. Addition of AmB to the double combinations resulted in increased FIC indices for A. fumigatus and A. flavus. By contrast, AmB increased the synergism of the double combinations decreasing FIC indices for A. terreus (P < 0.05). RAV and VOR displayed similar synergistic activity with CAS. The addition of sub-inhibitory amphotericin B concentrations reduced but did not eliminate the synergistic interaction between the echinocandin and triazole against A. fumigatus and A. flavus, while it increased the synergy against A. terreus.

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Combination antifungal therapy: what can and should we expect?

Cited by 33 publications

References 66 publications

RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

An update on the pharmacoeconomics of antifungal pharmacotherapy

Comparative pharmacodynamic interaction analysis of triple combinations of caspofungin and voriconazole or ravuconazole with subinhibitory concentrations of amphotericin B againstAspergillusspp.

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