Treatment of Experimental Zygomycosis in Guinea Pigs with Azoles and with Amphotericin B

Cutsem, J. Van; Gerven, F. Van; Fransen, J.; Janssen, P. A. J.

doi:10.1159/000238681

Cited by 28 publications

(20 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, cultures showed that spores remained viable in the tissues. These results are in accordance with previous studies that showed that amphotericin B prolonged survival in infected animals but did not clear the fungus from the organs (16,28). The two azoles tested in this study were not effective in vivo against R. oryzae despite their relatively low MICs, and similar results have been reported for itraconazole (16,28).…”

supporting

confidence: 93%

See 1 more Smart Citation

Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis

Dannaoui

Meis

Loebenberg³

et al. 2003

Antimicrob Agents Chemother

154

117

View full text Add to dashboard Cite

Three isolates of zygomycetes were used to produce a disseminated infection in nonimmunocompromised mice. Against all zygomycete strains, amphotericin B significantly prolonged survival. Itraconazole was inactive against Rhizopus microsporus and Rhizopus oryzae but was partially active against Absidia corymbifera. Posaconazole had no beneficial effects against R. oryzae but showed partial activity against A. corymbifera. Posaconazole had a clear dose-response effect against R. microsporus

show abstract

supporting

confidence: 93%

“…The other antifungal agents, including the azoles, are considered ineffective (11,20). Nevertheless, in vitro susceptibility data have been limited to a small number of isolates, and there have been few in vivo studies in animal models (3,6,8,14,16,21,24,27,28). Moreover, zygomycetes constitute a heterogeneous group for antifungal susceptibility (2).…”

mentioning

confidence: 99%

Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis

Dannaoui

Meis

Loebenberg³

et al. 2003

Antimicrob Agents Chemother

154

117

View full text Add to dashboard Cite

show abstract

“…Consistent with these results, previous studies using a similar model of disseminated zygomycosis in nonneutropenic mice have demonstrated that amphotericin B prolonged survival in infected animals but did not clear the fungus from any of the organs tested (19). Using nonimmunocompromised guinea pigs, similar results were obtained in animals infected with R. oryzae (19,33). Only one study showed amphotericin B clearing the fungal infection from most of the organs in guinea pigs infected with R. microsporus (33).…”

mentioning

confidence: 61%

“…Amphotericin B is the treatment of choice for these infections, and the other antifungal drugs, including the azoles, are considered ineffective against zygomycetes (13,28). Nevertheless, in vitro susceptibility data for zygomycetes obtained with standardized techniques have been limited to a small number of isolates and there have been few studies that examine the in vivo efficacy of antifungals in experimentally infected animals (7,8,19,30,31,33).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Antifungal Therapy in a Nonneutropenic Murine Model of Zygomycosis

Dannaoui

Mouton

Meis

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Three isolates of zygomycetes belonging to three different genera (Rhizopus microsporus, Absidia corymbifera, and Apophysomyces elegans) were used to produce a disseminated infection in nonimmunocompromised mice. The therapeutic efficacy of amphotericin B, given intraperitoneally at doses ranging from 0.5 to 4.5 mg/kg of body weight/day, oral itraconazole at 100 mg/kg/day, and oral terbinafine at 150 mg/kg/day was evaluated in this model. The markers of antifungal efficacy were the median survival time, the mortality rate, and the percentage of infected organs. Organ culture was performed along with microscopic direct examinations of tissues to assess the presence of an active infection. An acute and lethal infection was obtained in untreated mice challenged with each of the three strains. The data obtained for direct examinations and qualitative cultures indicate that, due to the nonseptate nature of the hyphae, each technique gives different information and should be used together with the others. Against all three strains, amphotericin B yielded a 90 to 100% survival rate. Itraconazole was inactive against R. microsporus but significantly reduced mortality in mice infected with A. corymbifera or A. elegans. Terbinafine had no beneficial effects against R. microsporus and A. corymbifera despite documented absorption of the drug. Overall, only limited correlations were observed between MICs determined in vitro and in vivo efficacy of the drugs. The efficacy of itraconazole in these models of zygomycosis suggests that this drug, as well as the new azole compounds presently under development, warrants close evaluation.

show abstract

“…Furthermore, animal studies revealed that itraconazole was completely ineffective against Rhizopus and Mucor spp. even though the isolates were susceptible in vitro (28,29,159). In contrast, itraconazole did have activity in vivo against a hypersusceptible strain of Absidia (MIC, 0.03 g/ml).…”

Section: Antifungal Therapymentioning

confidence: 91%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

View full text Add to dashboard Cite

Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement

show abstract

Treatment of Experimental Zygomycosis in Guinea Pigs with Azoles and with Amphotericin B

Cited by 28 publications

References 4 publications

Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis

Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis

Efficacy of Antifungal Therapy in a Nonneutropenic Murine Model of Zygomycosis

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

Contact Info

Product

Resources

About