In Vitro Interactions of Calcineurin Inhibitors with Conventional Antifungal Agents Against the Yeast Form of Penicillium marneffei

2014 ◽  
Vol 178 (3-4) ◽  
pp. 217-220 ◽  
Author(s):  
Dongdong Mo ◽  
Xin Li ◽  
Lili Wei ◽  
Chenghang Sun ◽  
Hao Liang ◽  
...  
2004 ◽  
Vol 48 (5) ◽  
pp. 1664-1669 ◽  
Author(s):  
William J. Steinbach ◽  
Wiley A. Schell ◽  
Jill R. Blankenship ◽  
Chiatogu Onyewu ◽  
Joseph Heitman ◽  
...  

ABSTRACT The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly called rapamycin) exhibit in vitro and in vivo activity against Candida albicans, Cryptococcus neoformans, and Saccharomyces cerevisiae, including fungicidal synergy with azole antifungals. We report here that both FK506 and CY exhibit a clear in vitro positive interaction with caspofungin against Aspergillus fumigatus by disk diffusion, microdilution checkerboard, and gross and microscopic morphological analyses. Microscopic morphological analyses indicate that the calcineurin inhibitors delay filamentation, and in combination with caspofungin there is a positive interaction. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and existing antifungal agents to augment activity against A. fumigatus.


2009 ◽  
Vol 53 (8) ◽  
pp. 3549-3551 ◽  
Author(s):  
Eric Dannaoui ◽  
Patrick Schwarz ◽  
Olivier Lortholary

ABSTRACT The in vitro interaction of antifungals with immunosuppressive drugs was evaluated against zygomycetes. The combination of amphotericin B with cyclosporine, rapamycin, or tacrolimus was synergistic for 90%, 70%, and 30% of the isolates, respectively. For posaconazole, itraconazole, and ravuconazole, synergy was more frequently observed with cyclosporine than with rapamycin or tacrolimus and antagonistic interactions were rarely noted. In summary, calcineurin inhibitors and rapamycin can be synergistic in vitro with amphotericin B and azoles against zygomycetes.


2006 ◽  
Vol 50 (10) ◽  
pp. 3312-3316 ◽  
Author(s):  
Stephen P. Saville ◽  
Anna L. Lazzell ◽  
Alexander P. Bryant ◽  
Angelika Fretzen ◽  
Alex Monreal ◽  
...  

ABSTRACT Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus the development of active disease as characterized by damage to the host leading to mortality. To address this issue, we genetically engineered a C. albicans tet-NRG1 strain in which filamentation and virulence can be modulated both in vitro and in vivo simply by the presence or absence of doxycycline (DOX): this strain enabled us, in a prior study, to demonstrate that yeast-form cells were able to infect the deep organs but caused no disease unless filamentation (induced by the addition of DOX) was allowed to occur. In the present study, we examined whether inhibiting filamentation (by withdrawing the DOX) at 24 or 48 h postinfection could serve as an effective therapeutic intervention against candidiasis. The results obtained indicate that DOX removal led to an alteration in the morphology of the infecting fungal cells and a dramatic increase in survival, but as with conventional antifungal drug therapy regimens, mortality rates increased markedly the longer this intervention was delayed. These observations reinforce the importance of invasive filamentous growth in causing the damage to the host and the lethality associated with active disease and suggest this process could be fruitfully targeted for the development of new antifungal agents.


2004 ◽  
Vol 48 (12) ◽  
pp. 4922-4925 ◽  
Author(s):  
William J. Steinbach ◽  
Nina Singh ◽  
Jackie L. Miller ◽  
Daniel K. Benjamin ◽  
Wiley A. Schell ◽  
...  

ABSTRACT We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin B, voriconazole, and caspofungin) and three immunosuppressants (FK506, cyclosporine, and rapamycin). We were not able to detect a difference in calcineurin inhibitor antifungal activity against isolates from transplant recipients and nontransplant patients.


Author(s):  
Lucia Brescini ◽  
Simona Fioriti ◽  
Gianluca Morroni ◽  
Francesco Barchiesi

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.


2019 ◽  
Vol 184 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Tatiana Borba Spader ◽  
Mauricio Ramírez-Castrillón ◽  
Patricia Valente ◽  
Sydney Hartz Alves ◽  
Luiz Carlos Severo

1984 ◽  
Vol 26 (6) ◽  
pp. 322-328 ◽  
Author(s):  
Angela Restrepo ◽  
Catalina de Bedoutand Angela M. Tabares

A study was conducted to determine the susceptibility of P. brasiliensis yeast form to amphotericin B (A), ketoconazole (K), 5-fluorocytosine (5-FC) and rifampin (R). The three isolates tested produced minimal inhibitory concentrations (MICs) (mcg/ml) in the following range: A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 and R: 40-80. The minimal fungicidal concentrations (MFC) were several times higher than the corresponding MICs. Precise MFC for 5-FC were not obtained (> 500 mcg/ml). Combination of K plus A proved synergic, with the fractional inhibitory concentration (FIC) indices revealing synergy when the drugs were combined at the 1 to 1 and 1 to 5 MIC ratios. R (40 mcg/ml) appeared to antagonize K. These results indicate promise for the combined use of K plus A as a therapeutical regimen.


2008 ◽  
Vol 31 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Susana Córdoba ◽  
Laura Rodero ◽  
Walter Vivot ◽  
Rubén Abrantes ◽  
Graciela Davel ◽  
...  

2021 ◽  
Vol 7 (9) ◽  
pp. 727
Author(s):  
Lucia Brescini ◽  
Simona Fioriti ◽  
Gianluca Morroni ◽  
Francesco Barchiesi

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations against dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies and 31 articles referring to case reports or clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts or essential oils, calcineurin inhibitors, peptides, disinfectant agents, and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections, an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e., terbinafine, griseofulvin, or azole—mainly itraconazole) plus a topical medication (i.e., azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful to accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available so far, it is desirable to continue the research in this field.


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