Time-Kill Curves Studies with Amphotericin B Against Cryptococcus neoformans/C. gattii Species Complex Clinical Isolates

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

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Molecular typing, in vitro susceptibility and virulence of Cryptococcus neoformans/Cryptococcus gattii species complex clinical isolates from south‐eastern Brazil

Mycoses ◽

10.1111/myc.13174 ◽

2020 ◽

Vol 63 (12) ◽

pp. 1341-1351

Author(s):

Patrícia Helena Grizante Barião ◽

Ludmilla Tonani ◽

Tiago Alexandre Cocio ◽

Roberto Martinez ◽

Érika Nascimento ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Molecular Typing ◽

Species Complex ◽

Cryptococcus Gattii ◽

Clinical Isolates ◽

In Vitro Susceptibility ◽

South Eastern ◽

Eastern Brazil

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In vitro susceptibilities of clinical and environmental isolates of Cryptococcus neoformans to five antifungal drugs.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.3.822 ◽

1996 ◽

Vol 40 (3) ◽

pp. 822-824 ◽

Cited By ~ 35

Author(s):

S P Franzot ◽

J S Hamdan

Keyword(s):

Cryptococcus Neoformans ◽

Amphotericin B ◽

Clinical Laboratory ◽

Antifungal Drugs ◽

Clinical Isolates ◽

National Committee ◽

Environmental Isolates ◽

Susceptibility Data

A total of 53 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates, were tested for their susceptibilities to amphotericin B, 5-flucytosine, ketoconazole, fluconazole, and itraconazole. The tests were performed according to the National Committee of Clinical Laboratory Standards recommendations (document M27-P). In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates. This paper represents the first contribution in which susceptibility data for Brazilian C. neoformans isolates are provided.

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Evaluation of amphotericin B and flucytosine in combination against Candida albicans and Cryptococcus neoformans using time-kill methodology

Diagnostic Microbiology and Infectious Disease ◽

10.1016/s0732-8893(01)00297-8 ◽

2001 ◽

Vol 41 (3) ◽

pp. 121-126 ◽

Cited By ~ 29

Author(s):

Douglas J. Keele ◽

Veronica C. DeLallo ◽

Russell E. Lewis ◽

Erika J. Ernst ◽

Michael E. Klepser

Keyword(s):

Candida Albicans ◽

Cryptococcus Neoformans ◽

Amphotericin B ◽

Time Kill

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Broth Microdilution and Time–Kill Testing of Caspofungin, Voriconazole, Amphotericin B and their Combinations Against Clinical Isolates of Candida krusei

Mycopathologia ◽

10.1007/s11046-011-9459-x ◽

2011 ◽

Vol 173 (1) ◽

pp. 27-34 ◽

Cited By ~ 3

Author(s):

Yasemin Oz ◽

Ilknur Dag ◽

Nuri Kiraz

Keyword(s):

Amphotericin B ◽

Candida Krusei ◽

Clinical Isolates ◽

Broth Microdilution ◽

Time Kill

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Molecular typing of clinical isolates of Cryptococcus neoformans/Cryptococcus gattii species complex from Northeast Mexico

Folia Microbiologica ◽

10.1007/s12223-015-0409-8 ◽

2015 ◽

Vol 61 (1) ◽

pp. 51-56 ◽

Cited By ~ 5

Author(s):

Gloria M. González ◽

Néstor Casillas-Vega ◽

Elvira Garza-González ◽

Romel Hernández-Bello ◽

Gildardo Rivera ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Molecular Typing ◽

Species Complex ◽

Cryptococcus Gattii ◽

Clinical Isolates

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In vitro susceptibility to antifungal agents of clinical and environmental Cryptococcus neoformans isolated in Southern of Brazil

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652001000500006 ◽

2001 ◽

Vol 43 (5) ◽

pp. 267-270 ◽

Cited By ~ 14

Author(s):

Sydney Hartz ALVES ◽

Loiva T. OLIVEIRA ◽

Jane M. COSTA ◽

Irina LUBECK ◽

Agnes Kiesling CASALI ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Amphotericin B ◽

Antifungal Agents ◽

Susceptibility Testing ◽

Clinical Isolates ◽

Environmental Isolates ◽

Aids Patients ◽

In Vitro Susceptibility ◽

Minimal Inhibitory Concentrations

The purpose of the present study was to compare the susceptibility to four antifungal agents of 69 Cryptococcus neoformans strains isolated from AIDS patients with that of 13 C. neoformans strains isolated from the environment. Based on the NCCLS M27-A methodology the Minimal Inhibitory Concentrations (MICs) obtained for amphotericin B, itraconazole and ketoconazole were very similar for clinical and environmental isolates. Clinical isolates were less susceptible to fluconazole than environmental isolates. The significance of these findings and aspects concerning the importance, role and difficulties of C. neoformans susceptibility testing are also discussed.

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In Vitro Interaction of Flucytosine with Conventional and New Antifungals against Cryptococcus neoformans Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.10.3361-3364.2003 ◽

2003 ◽

Vol 47 (10) ◽

pp. 3361-3364 ◽

Cited By ~ 27

Author(s):

Patrick Schwarz ◽

Françoise Dromer ◽

Olivier Lortholary ◽

Eric Dannaoui

Keyword(s):

Cryptococcus Neoformans ◽

Amphotericin B ◽

Clinical Isolates ◽

In Vitro Interaction

ABSTRACT 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.

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