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Eric Dannaoui

Publications and source records attributed to Eric Dannaoui.

18 recordsLinked to original sources
PubMed2006

Combination of amphotericin B with flucytosine is active in vitro against flucytosine-resistant isolates of Cryptococcus neoformans.

The combination of flucytosine and amphotericin B was tested against 10 flucytosine-resistant isolates of Cryptococcus neoformans by checkerboard, killing curves, and Etest. Although differences were observed depending on the technique used, antagonism was never observed. The synergistic interaction was related to the mechanism of flucytosine resistance of the isolates.

Amphotericin B↗
PubMed2006

Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis.

Whether or not flucytosine should be administered to patients infected with Cryptococcus neoformans isolates found to be resistant to flucytosine in vitro remains a controversial issue. Thus, the efficacy of amphotericin B and flucytosine in combination was investigated by mortality and fungal burden studies in a murine model of disseminated cryptococcosis using two clinical isolates of Cryptococcus neoformans, one susceptible and one resistant (i.e., 64 microg/ml) to flucytosine. Amphotericin B was given intraperitoneally at 0.25 or 0.5 mg/kg/day, while flucytosine was given at 100 or 250 mg/kg/day orally. Treatment was started 24 h or day 6 after inoculation and continued for 5 days in fungal burden and mortality studies, respectively. The combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day was significantly more effective than monotherapies for reducing fungal burden in brain, spleen, and lungs after infection by the flucytosine-susceptible isolate and in brain and spleen for the flucytosine-resistant isolate. For the flucytosine-resistant isolate, the combination of amphotericin B at 0.5 mg/kg/day with flucytosine at 100 mg/kg/day was significantly better than monotherapies for reducing the fungal burden in the brain. Survival obtained after the combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day increased compared to that obtained with monotherapies for both isolates, but the difference was statistically significant only for the flucytosine-susceptible isolate. Antagonism was never observed. This study demonstrates the beneficial effect of the addition of flucytosine to amphotericin B against experimental disseminated cryptococcal infection even when the C. neoformans isolate is resistant to flucytosine.

Amphotericin B↗
PubMed2006

Molecular identification of black-grain mycetoma agents.

Black-grain mycetomas are subcutaneous devastating chronic infections due to several dematiaceous fungi. They are diagnosed mostly in tropical countries. Identification of these fungi with standard mycological procedures is difficult because of their poor or delayed sporulation. The aim of this study was thus to assess the accuracy of molecular identification of these fungi. A total of 54 strains, mostly of clinical origin, were used, including 15 Madurella mycetomatis, 6 Madurella grisea, 12 Leptosphaeria senegalensis, 4 Leptosphaeria tompkinsii, 6 Pyrenochaeta spp., 4 Curvularia lunata, and 7 Exophiala jeanselmei strains. The internal transcribed spacer 1 (ITS1)-5.8S-ITS2 DNA region was amplified by using universal fungal primers and sequenced. Both intra- and interspecies sequence similarities were assessed. Madurella mycetomatis appeared to be a homogeneous species. More intraspecies variations were found for C. lunata and E. jeanselmei, leading, in some instances, to changes in the initial identification. L. senegalensis and L. tompkinsii showed intraspecies similarities of >99%, but similarity between the two species was <88%. Intergenera and interspecies variations were important, with sequence homologies of <81% between genera. In contrast, Pyrenochaeta romeroi and M. grisea appeared to be heterogeneous, with intraspecies similarities of 40 to 100% and 53 to 100%, respectively, which suggest either erroneous identification or the need for taxonomic revision. Epidemiological and therapeutic studies could benefit from a precise identification of the fungi responsible for black-grain mycetoma based not only on phenotypical characteristics but also on ITS sequencing.

DNA, Fungal↗
PubMed2006

Molecular identification of zygomycetes from culture and experimentally infected tissues.

Mucormycosis is an emerging infection associated with a high mortality rate. Identification of the causative agents remains difficult and time-consuming by standard mycological procedures. In this study, internal transcribed spacer (ITS) sequencing was validated as a reliable technique for identification of Zygomycetes to the species level. Furthermore, species identification directly from infected tissues was evaluated in experimentally infected mice. Fifty-four Zygomycetes strains belonging to 16 species, including the most common pathogenic species of Rhizopus spp., Absidia spp., Mucor spp., and Rhizomucor spp., were used to assess intra- and interspecies variability. Ribosomal DNA including the complete ITS1-5.8S-ITS2 region was amplified with fungal universal primers, sequenced, and compared. Overall, for a given species, sequence similarities between isolates were >98%. In contrast, ITS sequences were very different between species, allowing an accurate identification of Zygomycetes to the species level in most cases. Six species (Rhizopus oryzae, Rhizopus microsporus, Rhizomucor pusillus, Mucor circinelloides, and Mucor indicus) were also used to induce disseminated mucormycosis in mice and to demonstrate that DNA extraction, amplification of fungal DNA, sequencing, and molecular identification were possible directly from frozen tissues.

Amino Acid Sequence↗
PubMed2006

Successful treatment of black-grain mycetoma with voriconazole.

Fungal mycetoma (or eumycetoma) are endemic diseases in tropical areas that have economic effects because of their chronic and disabling evolution. Classic treatments include surgery and antifungal drugs, but these have multiple side effects. We report a case of black-grain fungal mycetoma successfully treated with voriconazole without side effects. The duration of the treatment remains unclear, but must be prolonged because of the frequency of relapses.

Antifungal Agents↗
PubMed2005

Antifungal combinations.

The increase in fungal infections and the change in fungal epidemiology is caused by the extensive use of antifungal agents to treat fungal infections that are being diagnosed in severly immunocompromised hosts. In addition, opportunistic fungal infections resistant to antifungal drugs have become increasingly common, and the armamentarium for treatment remains limited. A possible approach to overcoming these problems is to combine antifungal drugs, especially if the mechanisms of action are different. The in vitro test is the first step to evaluate possible antifungal combinations. In this chapter, the three most frequently used metholodologies are described: checkerboard, E-test, and time-kill curves. The description of each technique and intrepretaion of the results are addressed in detail.

Antifungal Agents↗
PubMed2004

Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered from treated patients.

Two-hundred sequential Aspergillus fumigatus isolates recovered from 26 immunocompromised patients with invasive aspergillosis or bronchial colonization were tested for their in vitro susceptibility to posaconazole, itraconazole, voriconazole, terbinafine and amphotericin B. Twenty-one patients were treated with amphotericin B and/or itraconazole. Antifungal susceptibilities of the isolates recovered before treatment were not significantly different from those of isolates recovered after the onset of antifungal therapy. The highest MICs were 0.125, 0.5, 0.5, 1 and 1 microg ml(-1) for posaconazole, itraconazole, voriconazole, terbinafine and amphotericin B, respectively. It is concluded that the emergence of resistance in A. fumigatus during antifungal therapy with amphotericin B or itraconazole is an uncommon phenomenon.

Amphotericin B↗
PubMed2004

In vitro evaluation of double and triple combinations of antifungal drugs against Aspergillus fumigatus and Aspergillus terreus.

Microdilution broth checkerboard techniques based on the National Committee for Clinical Laboratory Standards methodology were used to study double and triple antifungal combinations against clinical isolates of Aspergillus fumigatus and A. terreus. The influences of the end-point definition (partial or complete inhibition) and the mode of reading (visually or spectrophotometrically) were determined. Interactions between antifungal drugs were also evaluated by agar diffusion tests. Combinations of caspofungin with either amphotericin B or voriconazole were additive for all the isolates, and antagonism was not observed. The interaction between caspofungin and flucytosine was synergistic for 62% of the isolates. In contrast, the interaction between voriconazole and flucytosine was never synergistic and antagonism was noted for 93% of the isolates. The triple combination of caspofungin with flucytosine and amphotericin B was synergistic for all the isolates tested. The triple combination of caspofungin with flucytosine and voriconazole was also mostly synergistic; but complex interactions were obtained for some isolates, with synergy or antagonism depending on the concentrations of caspofungin and voriconazole. Analysis of the influence of the reading technique on the results showed that spectrophotometric reading was a good alternative to the recommended visual reading. The results of these in vitro tests suggest that the activity of flucytosine as part of a double combination with caspofungin and as part of a triple combination with caspofungin and amphotericin B against Aspergillus spp. warrants further investigations. Animal studies are needed to evaluate the in vivo efficacies of these combinations.

Antifungal Agents↗
PubMed2003

In vitro susceptibilities of zygomycetes to conventional and new antifungals.

In vitro susceptibilities of 36 zygomycete isolates, belonging to six genera, to itraconazole, posaconazole, voriconazole, terbinafine, amphotericin B and 5-fluorocytosine were determined by using a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M-38P reference method. The influence of incubation time on MIC values, and the performance of a spectrophotometric method for MIC determination in comparison with the visual reference method, were also evaluated. Amphotericin B was active against most of the isolates. All the isolates were highly resistant to 5-fluorocytosine (MICs > 256 mg/L). Voriconazole was significantly less active than the other drugs with an overall MIC(90) (MIC at which 90% of the isolates were inhibited) of 32 mg/L. In contrast, posaconazole showed good activity (MIC(90) 1 mg/L). A wide range of MICs, from 0.03 to > or =32 mg/L, was obtained for itraconazole and terbinafine. Differences in susceptibility between and within genera were noted. Rhizopus spp. were significantly less susceptible to itraconazole, posaconazole, terbinafine and amphotericin B than Absidia spp., and less susceptible than Mucor spp. to amphotericin B. Terbinafine appeared to be more active against Rhizopus microsporus than against Rhizopus oryzae (geometric mean MIC of 0.15 and 64 mg/L, respectively). The activity of the drugs was dependent on the incubation period. A significant increase in MICs was noted between 24 and 48 h of incubation. On the other hand, the two methods used for MIC determination (visual and spectrophotometric readings) showed good agreement. These results suggest that the zygomycetes are a heterogeneous group for antifungal susceptibility. Some of the conventional and new antifungals are effective in vitro; their efficacies in vivo remain to be determined. The spectrophotometric method appears to be a valuable alternative to the visual method for MIC determination for zygomycetes.

Antifungal Agents↗
PubMed2003

In vitro interaction of flucytosine with conventional and new antifungals against Cryptococcus neoformans clinical isolates.

Combinations of flucytosine with conventional and new antifungals were evaluated in vitro against 30 clinical isolates of Cryptococcus neoformans. Synergy determined by checkerboard analysis was observed with combinations of fluconazole, itraconazole, voriconazole, amphotericin B, and caspofungin with flucytosine against 77, 60, 80, 77, and 67% of the isolates, respectively. Antagonism was never observed. Killing curves showed indifferent interactions between triazoles and flucytosine and synergy between amphotericin B and flucytosine.

Antifungal Agents↗
PubMed2003

Activity of posaconazole in treatment of experimental disseminated zygomycosis.

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.

Absidia↗
PubMed2002

In vitro susceptibilities of Zygomycota to polyenes.

The in vitro activity of polyenes was determined for 36 isolates of Zygomycota including Rhizopus spp. (15), Absidia corymbifera (10), Mucor spp. (6), Rhizomucor spp. (3), Cunninghamella bertholletiae (1) and Apophysomyces elegans (1). All isolates were tested with amphotericin B, heated amphotericin B and nystatin by a broth microdilution test. There were no significant differences between heated and unheated solutions of amphotericin B in terms of their antifungal activities. The MICs of amphotericin B for most of the strains were <2 mg/L. For all isolates, nystatin was significantly less active than amphotericin B (P < 0.001). The one C. bertholletiae and one A. elegans isolates were less susceptible to amphotericin B (MICs 2 mg/L) and were also less susceptible to nystatin.

Amphotericin B↗
PubMed2002

In vitro synergistic interaction between amphotericin B and pentamidine against Scedosporium prolificans.

To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Laboratory Standards M38-P guidelines. The interaction between the drugs was analyzed using fractional inhibitory concentration index (FICI) analysis and response surface modeling. Amphotericin B alone was inactive against all the isolates. The geometric mean MIC for pentamidine was 57 micro g/ml (range, 8 to 256 micro g/ml; MIC at which 50% of the isolates tested were inhibited [MIC(50)], 64 micro g/ml; MIC(90), 128 micro g/ml). The combination was synergistic against 28 of 30 isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface modeling analysis. Antagonism was not observed.

Amphotericin B↗
PubMed2002

Efficacy of antifungal therapy in a nonneutropenic murine model of zygomycosis.

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.

Absidia↗
PubMed2002

In vitro susceptibilities of zygomycetes to combinations of antimicrobial agents.

Combinations of antimicrobial agents were tested against 35 strains of zygomycetes. The interaction between amphotericin B and rifampin was synergistic or additive. Flucytosine alone was inactive and, upon combination with amphotericin B, synergy was not achieved. The combination of amphotericin B with terbinafine was synergistic for 20% of strains, and the interaction between terbinafine and voriconazole was synergistic for 44% of strains. Antagonism was not observed.

Amphotericin B↗
PubMedDate not supplied

[Methods for in vitro antifungal susceptibility testing].

During the last years, a large amount of work has been completed to improve the methods used for in vitro antifungal susceptibility testing. Reference techniques are currently available both for yeasts and filamentous fungi, but in some instances, technical improvement are needed. Etest is another well standardized method that can be used as an alternative on a routine basis in the clinical microbiology laboratory. Studies of in vitro-in vivo correlations have led to the definition of susceptibility breakpoints for yeasts for fluconazole, itraconazole, and flucytosine.

Antifungal Agents↗