In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against
            <i>Scedosporium prolificans</i>

Afeltra, Javier; Dannaoui, Éric; Meis, Jacques F.; Rodríguez-Tudela, Juan Luis; Verweij, Paul E.

doi:10.1128/aac.46.10.3323-3326.2002

Cited by 39 publications

(23 citation statements)

References 24 publications

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“…Some investigators have suggested using a combination of the FICI and RSM approach and have shown that results obtained from the two correlate well (2,222,223). However, the inherent complexity of the RSM method makes it less attractive as the primary method to evaluate the interactions between antifungal agents in combination, and the FICI method has remained the method of choice for most studies.…”

Section: Checkerboard Methodsmentioning

confidence: 99%

“…In a recent study, the in vitro efficacy of AmB and PN, alone or in combination, against 30 clinical isolates of S. prolificans was determined by using the FICI and RSM methods (2). These investigators showed that the combination of AmB-plus-PN exhibited synergy against 28 of 30 isolates (93.3%) and aditivity for 2 of 30 isolates (6.7%), while the RSM method predicted 100% synergy (2). Although these combinations showed promise during in vitro and in vivo studies, their clinical utility can be determined only after further studies.…”

Section: Combinations Of Antifungal Antibacterial and Anticancer Agmentioning

confidence: 99%

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Combination Treatment of Invasive Fungal Infections

et al. 2005

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The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections

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Section: Checkerboard Methodsmentioning

confidence: 99%

Section: Combinations Of Antifungal Antibacterial and Anticancer Agmentioning

confidence: 99%

Combination Treatment of Invasive Fungal Infections

et al. 2005

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“…S. prolificans is resistant in vitro to virtually all antifungal agents and has responded poorly to voriconazole, with only 3 of 10 patients improving (1)(2)(3)(8)(9)(10). A recent review of scedosporiosis in solid organ transplant patients reported only four survivors among 18 patients with S. prolificans infection (5).…”

mentioning

confidence: 99%

Caspofungin and Liposomal Amphotericin B Therapy of Experimental Murine Scedosporiosis

Bocanegra

Najvar

Hernandez

et al. 2005

Antimicrob Agents Chemother

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Immunosuppressed mice were infected intravenously with conidia of Scedosporium prolificans. Treatment was begun 1 day later with liposomal amphotericin B, caspofungin, or both drugs initiated concurrently. Amphotericin B and caspofungin were each effective, but combined therapy did not appear to offer advantages over liposomal amphotericin B alone.Scedosporium apiospermum and S. prolificans cause up to 10% of invasive mycelial fungal infections in predisposed patients (4, 7). S. prolificans is resistant in vitro to virtually all antifungal agents and has responded poorly to voriconazole, with only 3 of 10 patients improving (1)(2)(3)(8)(9)(10). A recent review of scedosporiosis in solid organ transplant patients reported only four survivors among 18 patients with S. prolificans infection (5).In this setting, we evaluated a new echinocandin, caspofungin, in the treatment of S. prolificans infection. We compared the changes in survival and CFU (as measurements of tissue burden) in neutropenic mice undergoing an acute infection with S. prolificans. In addition to caspofungin, we evaluated liposomal amphotericin B alone and in combination with caspofungin.S. prolificans strain 95-2409 was cultured on potato flake agar. Conidia were washed, filtered, counted in a hemacytometer, and suspended in sterile saline. The MIC was determined using the CLSI (formerly NCCLS) method adapted for mycelial fungi, along with the minimal effective concentration according to the method of Kurtz et al. (6). The MIC of caspofungin and liposomal amphotericin B was 8 g/ml at 24 and 48 h of incubation. The minimal effective concentration of caspofungin was 8 g/ml at 24 and 48 h.Male outbred ICR mice were made neutropenic by a single intraperitoneal (i.p.) dose of cyclophosphamide at 200 mg/kg of body weight 1 day prior to infection. Mice were infected intravenously (i.v.) with conidia in a 0.2-ml volume. Beginning 1 day after infection, control mice were treated with sterile water i.p., liposomal amphotericin B (Astellas Pharma Inc., formally Fujisawa) i.v. at 10, 20, or 30 mg/kg once daily, or caspofungin (Merck & Co., Inc) i.p. at 5, 10, or 20 mg/kg once daily. For survival studies, groups of 10 to 12 mice were treated from day 1 through day 10, with observation through day 21 or day 25. Mice which appeared moribund were sacrificed and considered to have died the next day. For studies of tissue burden, mice were treated from day 1 through day 7 after infection and sacrificed on day 8 for quantitative tissue cultures of kidneys. The log rank test was used for comparison of survival studies. The Mann-Whitney U test was used for comparison of CFU counts. Because of multiple comparisons, a P value of Յ0.02 was required for significance.Survival following infection with a low inoculum dose of S. prolificans is shown in Fig. 1A. Liposomal amphotericin B at a dose of 10 or 20 mg/kg significantly prolonged survival over that of controls (P Ͻ 0.0003), but 30 mg/kg appeared toxic. As shown in Fig. 1B, caspofungin at 5 mg/kg was ineffective, but 10...

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“…Administration of PNT is a well-established approach used for prophylaxis and treatment of pneumonia caused by Pneumocystis carinii, a microorganism that was recently classified taxonomically to be a fungus (21). PNT has also been shown to have in vitro activities against a variety of fungal pathogens, such as Candida albicans, Cryptococcus neoformans, Scedosporium prolificans, and Aspergillus terreus (1,2,5,20). Therefore, in this study, we evaluated the in vitro activities of PNT against 10 clinical isolates of Fusarium spp.…”

mentioning

confidence: 99%

Pentamidine Is Active In Vitro againstFusariumSpecies

Lionakis

Lewis

Samonis

et al. 2003

Antimicrob Agents Chemother

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Fusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates of Fusarium species (five Fusarium solani isolates and five non-F. solani isolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye staining. PNT had significant activities against all 10 Fusarium isolates. Non-F. solani isolates were more susceptible than F. solani isolates (P < 0.05). Additionally, PNT was fungicidal against all non-F. solani isolates, whereas it had fungistatic effects against four of the five F. solani isolates. PNT also exhibited greater activity against conidial than against hyphal development of the fungus. This fungicidal activity against non-F. solani Fusarium isolates was confirmed microscopically after staining of PNT-treated Fusarium oxysporum hyphae with the fluorescent viability dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC). The MICs at which 50% of the isolates were inhibited (2 g/ml for non-F. solani isolates and 4 g/ml for F. solani isolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 g/ml for non-F. solani isolates) were much lower than the PNT tissue concentrations previously reported in humans using conventional daily intravenous PNT dosing. Finally, PNT was more active against Fusarium isolates in a hypoxic environment of in vitro growth (P < 0.05). This finding may be clinically significant, because Fusarium, an angiotropic mold, causes tissue infarcts with resultant low tissue perfusion. Our findings suggest that PNT may have a role in the management of Fusarium infections. Future in vivo studies are needed to verify these in vitro findings.

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In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

Cited by 39 publications

References 24 publications

Combination Treatment of Invasive Fungal Infections

Combination Treatment of Invasive Fungal Infections

Caspofungin and Liposomal Amphotericin B Therapy of Experimental Murine Scedosporiosis

Pentamidine Is Active In Vitro againstFusariumSpecies

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