scholarly journals Apoptosis in Candida biofilms exposed to amphotericin B

2010 ◽  
Vol 59 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Rawya S. Al-Dhaheri ◽  
L. Julia Douglas
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Clinical Use ◽  
Caspase Activity ◽  
Persister Cells ◽  
Specific Staining ◽  
General Inhibitor ◽  
Staining Methods

Candida biofilms are resistant to a range of antifungal agents in current clinical use. The basis of this drug resistance is not clear, but in some cases it could be due to the presence of a small number of drug-tolerant or persister cells. In this study, specific staining methods were used to investigate the existence of persisters and apoptosis in Candida biofilms subjected to different concentrations of amphotericin B. Fluorescein diacetate staining revealed the presence of persisters in biofilms of one of two strains of Candida albicans tested, and in biofilms of Candida krusei and Candida parapsilosis. Caspase activity, indicative of apoptosis, was detected with SR-FLICA and (aspartyl)2-rhodamine 110 fluorochrome-based staining reagents in all of these biofilms. The general inhibitor of mammalian caspases, Z-VAD-FMK, when used at a low concentration (2.5 μM), increased the viability of drug-treated biofilms up to 11.5-fold (P <0.001 %). Seven specific caspase inhibitors had different effects on C. albicans biofilm viability, but inhibitors of caspases-1, −9, −5, −3 and −2 all significantly increased cell survival (40-fold, 8-fold, 3.5-fold, 1.9-fold and 1.7-fold, respectively). However, histone deacetylase (HDA) inhibitors enhanced the activity of amphotericin B for biofilms of all three Candida species. Sodium butyrate and sodium valproate, for example, when added concurrently with amphotericin B, completely eliminated biofilm populations of C. albicans. Overall, our results demonstrate an apoptotic process in amphotericin-treated biofilms of three Candida species. They also indicate that HDA inhibitors can enhance the action of the drug and in some cases even eradicate persister subpopulations, suggesting that histone acetylation might activate apoptosis in these cells.

scholarly journals Absence of Amphotericin B-Tolerant Persister Cells in Biofilms of Some Candida Species

2008 ◽  
Vol 52 (5) ◽  
pp. 1884-1887 ◽  
Author(s):  
Rawya S. Al-Dhaheri ◽  
L. Julia Douglas
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Cell Populations ◽  
Planktonic Cells ◽  
Persister Cells ◽  
Tolerant Cell

ABSTRACT Biofilms and planktonic cells of five Candida species were surveyed for the presence of persister (drug-tolerant) cell populations after exposure to amphotericin B. None of the planktonic cultures (exponential or stationary phase) contained persister cells. However, persisters were found in biofilms of one of two strains of Candida albicans tested and in biofilms of Candida krusei and Candida parapsilosis, but not in biofilms of Candida glabrata or Candida tropicalis. These results suggest that persister cells cannot solely account for drug resistance in Candida biofilms.

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

scholarly journals Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Wiley A. Schell ◽  
A. M. Jones ◽  
Katyna Borroto-Esoda ◽  
Barbara D. Alexander
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Wild Type ◽  
Content Type ◽  
Clinical Resistance ◽  
Excellent Activity ◽  
Candida Lusitaniae

ABSTRACT SCY-078 in vitro activity was determined for 178 isolates of resistant or susceptible Candida albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitaniae, and Candida parapsilosis, including 44 Candida isolates with known genotypic (FKS1 or FKS2 mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species.

scholarly journals Effect of pH onIn VitroSusceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

2012 ◽  
Vol 56 (3) ◽  
pp. 1403-1406 ◽  
Author(s):  
Claire S. Danby ◽  
Dina Boikov ◽  
Rina Rautemaa-Richardson ◽  
Jack D. Sobel
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Low Ph ◽  
Clinical Use ◽  
Effect Of Ph ◽  
Content Type ◽  
Clinical Observations

ABSTRACTThe treatment of vulvovaginal candidiasis (VVC) due toCandida glabratais challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite ofin vitrosusceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on thein vitroactivity of 11 antifungal agents against 40C. glabrataisolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibilityC. albicansstrains.In vitrosusceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH,C. glabrataisolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC90for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7,C. albicansstrains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitiveC. albicansisolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrentC. glabratavaginitis, clinicians should recognize the limitations ofin vitrosusceptibility testing utilizing pH 7.0.

Fluconazole, caspofungin, voriconazole in combination with amphotericin B

Open Medicine ◽  
2010 ◽  
Vol 5 (2) ◽  
pp. 194-197 ◽  
Author(s):  
Ayse Kalkanci ◽  
Murat Dizbay ◽  
Nuran Sari ◽  
Burce Yalcin ◽  
Isil Fidan ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Combination Treatment ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Test Methods ◽  
Antagonistic Activity ◽  
Test Method ◽  
Synergistic Activity ◽  
Combination Test

AbstractCombined antifungal therapy has been suggested to enhance the efficacy and reduce the toxicity of antifungal agents. The aim of the study was to investigate the in vitro synergistic activity of caspofungin, voriconazole, and fluconazole with amphotericin B against ten isolates of Candida parapsilosis and Candida albicans strains which were resistant to azoles or amphotericin B. Three different antifungal combinations (amphotericin B [AP] — caspofungin [CS], amphotericin B — fluconazole [FL], and AP — voriconazole [VO]) were evaluated for in vitro synergistic effect by the microdilution checkerboard and E-test methods. For the majority of strains, the combination test showed indifferent activity. Via the E-test method, synergistic activity was seen in 3 strains in response to AP-CS combination treatment and in one strain after administration of AP-FL; however, no synergy was observed in response to combination treatment with P-VO. Antagonistic activity was the result in 1 strain treated with AP-CS as well as in 6 strains treated with AP-FL and AP-VO combinations. Via the microdilution test, no synergistic activity was seen after treatment with all 3 combinations. Antagonistic activity was the result in 2 strains with AP-CS, in 6 strains with AP-VO and in 5 strains with AP-FL combinations. Agreement between the checkerboard and E-test methods was observed to be approximately 72%. These combinations may be used in the case of antifungal resistance.

scholarly journals Quality Control Limits for Broth Microdilution Susceptibility Tests of Ten Antifungal Agents

2000 ◽  
Vol 38 (9) ◽  
pp. 3457-3459 ◽  
Author(s):  
A. L. Barry ◽  
M. A. Pfaller ◽  
S. D. Brown ◽  
A. Espinel-Ingroff ◽  
M. A. Ghannoum ◽  
...  
Keyword(s):  
Quality Control ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Clinical Laboratory ◽  
Collaborative Study ◽  
Candida Krusei ◽  
National Committee ◽  
Broth Microdilution ◽  
Susceptibility Tests ◽  
Control Limits

Broth microdilution susceptibility tests of Candidaspecies have now been standardized by the National Committee for Clinical Laboratory Standards (NCCLS). An eight-laboratory collaborative study was carried out in order to document reproducibility of tests of Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258 by the NCCLS method. Replicate broth microdilution tests were used to define control limits for 24- and 48-h MICs of amphotericin B, flucytosine, fluconazole, voriconazole, ketoconazole, itraconazole, caspofungin (MK 0991), ravuconazole (BMS 207147), posaconazole (SCH 56592), and LY 303366.

scholarly journals Antifungal Resistance Pattern of Candida Species Isolated from High Vaginal Swabs of Women Attending a Hospital in Enugu State, Nigeria

2020 ◽  
pp. 62-72
Author(s):  
Joachim Ohiakwu Ezeadila ◽  
Ikechukwu Okoli ◽  
Christie Amaechi Oyeka
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Tropicalis ◽  
Candida Species ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Inhibition Zone ◽  
Candida Krusei ◽  
Antifungal Resistance ◽  
Resistance Pattern

There is an increase in non-albicans Candida (NAC) vulvovaginal candidiasis which is attributed to overuse of antifungal therapy and this has led to antifungal resistance. This study was aimed at determining the antifungal resistance pattern of some clinical isolates of Candida species. Eighty-eight (88) isolates were used which included Candida tropicalis (34), Candida Parapsilosis (21), Candida albicans (20), Candida krusei (7) and Candida glabrata (6). The drugs used were Fluconazole (25µg), Ketoconazole (10µg), Voriconazole (1µg), Nystatin (100Units), Amphotericin B (20µg), Flucytosine (1µg), Clotrimazole (10µg) and Itraconazole (50µg). The susceptibility testing was carried out using the M44-A standard method for yeast disk diffusion testing. Results showed that the percentages of Candida species resistant to Fluconazole, Ketoconazole, Voriconazole, Amphotericin B, Flucytosine, Clotrimazole and Itraconazole and Nystatin were 52.3%, 61.9%, 35.2%, 19.3%, 86.4%, 34.1%,  45.5% and 44.3%,  with inhibition zone diameters ≤14mm, ≤20mm, ≤13mm, <10mm, ≤11mm, ≤11mm, ≤13mm and no inhibition zone diameter respectively. Candida krusei was the most resistant species with 100% resistance to each of Fluconazole, Ketoconazole and Flucytosine. Candida tropicalis was the species with the highest susceptibility (79.4%) to Amphotericin B followed by Candida parapsilosis with inhibition zone diameters ≥15mm. While Candida glabrata showed 100% resistance to each of Flucytosine and Itraconazole, Candida albicans showed 100% resistance to Flucytosine only. Candida glabrata was the only Candida species with 0% resistance to Amphotericin B. The drug to which most of the Candida species were susceptible was Amphotericin B followed by Voriconazole while Flucytosine was the drug with the highest resistance followed by Ketoconazole and Fluconazole. The highest number of susceptible-dose dependent Candida isolates was observed with Ketoconazole (25%), followed by Clotrimazole and Itraconazole, each recording 23.9%. Based on the findings of the present study, Voriconazole is recommended for vaginal candidiasis especially in the study area and also especially for infections caused by Fluconazole-resistant Candida species. This suggests that routine sensitivity testing is pertinent to guiding the choice of antifungal therapy. Thus, indiscriminate use of antifungal drugs should be avoided to reduce the development and spread of resistance.

scholarly journals Constant Low Rate of Fungemia in Norway, 1991 to 1996

1998 ◽  
Vol 36 (12) ◽  
pp. 3455-3459 ◽  
Author(s):  
Per Sandven ◽  
Lars Bevanger ◽  
Asbjørn Digranes ◽  
Peter Gaustad ◽  
Hanne H. Haukland ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Antibiotic Use ◽  
Blood Cultures ◽  
Candida Krusei ◽  
University Hospitals ◽  
Local Hospital ◽  
The University ◽  
Isolated Species

Since 1991 information on yeast isolates from blood cultures has been recorded prospectively from all microbiological laboratories (5 university and 16 county or local hospital laboratories) in Norway (population, 4.3 million). From 1991 to 1996 a total of 571 episodes of fungemia in 552 patients occurred (1991, 109 episodes; 1992, 81 episodes; 1993, 93 episodes; 1994, 89 episodes; 1995, 98 episodes; and 1996, 101 episodes). The fungemia rates per 10,000 patient days were 0.29 in 1991 and 0.27 in 1996. The average rates for the years 1991 to 1996 were 0.37 for the university laboratories and 0.20 for the other laboratories. These rates are low compared to the rate (0.76) in five Dutch university hospitals in 1995 and the rate (2.0) in Iowa in 1991. The four most frequently isolated species wereCandida albicans (66%), Candida glabrata(12.5%), Candida parapsilosis (7.6%), and Candida tropicalis (6.4%). The incidences of both C. albicans (range, 63 to 73%) and C. glabrata (range, 8.4 to 15.7%) varied somewhat throughout this period, but no significant increase or decrease was noted. MICs of amphotericin B, flucytosine, and fluconazole were determined for 89% of the isolates. All were susceptible to amphotericin B, and only 29 (5.6%) strains had decreased susceptibility to flucytosine. All C. albicansisolates were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs, ≥16 μg/ml) did increase, from 9.6% in 1991 and 1992 to 12.2% in 1994, 16.1% in 1995, and 18.6% in 1996. This was largely due to increases in the percentages of resistant C. glabrata andCandida krusei strains in the last 2 years. Compared to the incidence in other countries, it is remarkable that Norway has such a low and constant incidence of fungemia. A possible reason for this difference might be a restricted antibiotic use policy in Norway.

Enhancement of the in vitro activity of amphotericin B against the biofilms of non-albicans Candida spp. by rifampicin and doxycycline

2007 ◽  
Vol 56 (5) ◽  
pp. 645-649 ◽  
Author(s):  
Mohamed El-Azizi
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Killing Activity

The in vitro activity of amphotericin B (AMB) alone and in combination with rifampicin (RIF) and doxycycline (DOX) was tested against the biofilms of 30 clinical isolates of non-albicans Candida (NAC) species namely, Candida parapsilosis, Candida krusei and Candida glabrata. The killing activity of AMB at 10×MIC was significantly increased in combination with either antibiotic. With RIF, the killing activity increased by 20.6, 23.5 and 14 % against the biofilms of C. parapsilosis, C. krusei and C. glabrata, respectively; with DOX, the killing activity increased by 30.64, 35.28 and 31.13 %, respectively. Pre-exposure of the isolates to the same combinations significantly reduced the number of colonized cells in the biofilms by 20, 25.14 and 13.07 % with RIF for C. parapsilosis, C. krusei and C. glabrata, respectively, and by 18.94, 24.52 and 29.15 % with DOX, respectively. The data showed that combination of RIF or DOX with AMB enhanced the killing activity of the antifungal agent against biofilms of NAC species. Whether such an effect operates against biofilm-associated infections needs to be clarified by further in vivo studies.

In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates ofCandida spp.

1998 ◽  
Vol 42 (1) ◽  
pp. 161-163 ◽  
Author(s):  
F. Marco ◽  
M. A. Pfaller ◽  
S. Messer ◽  
R. N. Jones
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
Candida Krusei ◽  
Antifungal Drugs ◽  
National Committee ◽  
In Vitro Activity ◽  
Medical Centers

ABSTRACT Voriconazole (formerly UK-109,496) is a new monotriazole antifungal agent which has potent activity against Candida,Cryptococcus, and Aspergillus species. We investigated the in vitro activity of voriconazole compared to those of fluconazole, itraconazole, amphotericin B, and flucytosine (5FC) against 394 bloodstream isolates of Candida (five species) obtained from more than 30 different medical centers. MICs of all antifungal drugs were determined by the method recommended by the National Committee for Clinical Laboratory Standards using RPMI 1640 test medium. Overall, voriconazole was quite active against all the yeast isolates (MIC at which 90% of the isolates are inhibited [MIC90], ≤0.5 μg/ml). Candida albicans was the most susceptible species (MIC90, 0.06 μg/ml) andCandida glabrata and Candida krusei were the least (MIC90, 1 μg/ml). Voriconazole was more active than amphotericin B and 5FC against all species except C. glabrata and was also more active than itraconazole and fluconazole. For isolates of Candida spp. with decreased susceptibility to fluconazole and itraconazole MICs of voriconazole were also higher. Based on these results, voriconazole has promising antifungal activity and further in vitro and in vivo investigations are warranted.

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