scholarly journals In Vitro Activities of Isavuconazole and Other Antifungal Agents against Candida Bloodstream Isolates

2007 ◽  
Vol 51 (5) ◽  
pp. 1818-1821 ◽  
Author(s):  
H. Seifert ◽  
U. Aurbach ◽  
D. Stefanik ◽  
O. Cornely
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Tertiary Care ◽  
Common Species ◽  
University Hospital ◽  
Phase Iii ◽  
Highly Active ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC50s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC50s/MIC90s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.

scholarly journals In Vitro Susceptibilities of Candida dubliniensisIsolates Tested against the New Triazole and Echinocandin Antifungal Agents

1999 ◽  
Vol 37 (3) ◽  
pp. 870-872 ◽  
Author(s):  
M. A. Pfaller ◽  
S. A. Messer ◽  
S. Gee ◽  
S. Joly ◽  
C. Pujol ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
National Committee ◽  
Mucosal Disease ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Investigational Agents ◽  
Multidrug Resistance Transporters

Candida dubliniensis is a newly recognized fungal pathogen causing mucosal disease in AIDS patients. Although preliminary studies indicate that most strains of C. dubliniensis are susceptible to established antifungal agents, fluconazole-resistant strains have been detected. Furthermore, fluconazole-resistant strains are easily derived in vitro, and these strains exhibit increased expression of multidrug resistance transporters, especially MDR1. Because of the potential for the development of resistant strains of C. dubliniensis, it is prudent to explore the in vitro activities of several of the newer triazole and echinocandin antifungals against isolates of C. dubliniensis. In this study we tested 71 isolates of C. dubliniensis against the triazoles BMS-207147, Sch 56592, and voriconazole and a representative of the echinocandin class of antifungal agents, MK-0991. We compared the activities of these agents with those of the established antifungal agents fluconazole, itraconazole, amphotericin B, and 5-fluorocytosine (5FC) by using National Committee for Clinical Laboratory Standards microdilution reference methods. Our findings indicate that the vast majority of clinical isolates of C. dubliniensis are highly susceptible to both new and established antifungal agents. Strains with decreased susceptibilities to fluconazole remained susceptible to the investigational agents as well as to amphotericin B and 5FC. The increased potencies of the new triazole and echinocandin antifungal agents may provide effective therapeutic options for the treatment of infections due to C. dubliniensis.

scholarly journals In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

1998 ◽  
Vol 42 (10) ◽  
pp. 2503-2510 ◽  
Author(s):  
Maurizio Del Poeta ◽  
Wiley A. Schell ◽  
Christine C. Dykstra ◽  
Susan K. Jones ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Inhibitory Compounds ◽  
Wide Range ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

scholarly journals CANDIDA SPECIES IN THE GENITAL TRACT OF WOMEN ATTENDING A UNIVERSITY HOSPITAL FOR GYNECOLOGICAL INTERVENTIONS

2017 ◽  
Vol 5 (1) ◽  
pp. 13
Author(s):  
Thais Chimati Felix ◽  
Ralciane De Paula Menezes ◽  
Marilia Cristina Berardi ◽  
Denise Von Dolinger de Brito Röder ◽  
Reginaldo Dos Santos Pedroso
Keyword(s):  
Candida Species ◽  
Genital Tract ◽  
Antifungal Agents ◽  
Positive Culture ◽  
Signs And Symptoms ◽  
Common Species ◽  
Reproductive Age ◽  
University Hospital ◽  
Gynecology And Obstetrics

Introduction: Vulvovaginal candidiasis occurs in about 75% of all women during reproductive age, and around half of those will have at least one recurrent episode. Objectives: To evaluate the occurrence of Candida species in the genital tract of women attending a clinic of Gynecology and Obstetrics at the University Hospital for gynecological interventions, related to signs and symptoms of infection and also to evaluate the susceptibility to antifungal agents of the Candida isolates. Methods and materials: Samples of vaginal secretions were taken of 128 women during gynecological and colposcopic examination, through sterile swab, to carry out culture for fungi. Susceptibility tests were performed for fluconazole, itraconazole, voriconazole, nystatin and amphotericin B. Results: Twenty (15.6%) patients had positive culture for yeasts identified as: C. albicans (57.1%), C. glabrata (19%), C. parapsilosis complex (4.8%), C. lipolytica (4.8%), Trichosporon sp (9.5%), and Rhodotorula sp (4.8%). Ninety women (70.3%) reported no symptoms and 38 (29.6%) were symptomatic. The most frequent complaints were: discharge, vulval itching, and dyspareunia. All isolates were susceptible to the antifungal agents tested, except for some isolates of C. parapsilosis complex, which showed in vitro resistance to itraconazole. Conclusions: Although Candida species were isolated in only some of the women, C. albicans was the most common species. The more frequent complaints were discharge and vulvar itching. Most of the isolates were susceptible to the antifungals tested.

scholarly journals In Vitro Activities of Three Licensed Antifungal Agents against Spanish Clinical Isolates of Aspergillus spp

2003 ◽  
Vol 47 (10) ◽  
pp. 3085-3088 ◽  
Author(s):  
Alicia Gomez-Lopez ◽  
Guillermo Garcia-Effron ◽  
Emilia Mellado ◽  
Araceli Monzon ◽  
Juan L. Rodriguez-Tudela ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Common Species ◽  
Medical Centers ◽  
Susceptibility Patterns ◽  
Skin Samples

ABSTRACT The aim of the present study was to identify retrospectively trends in the species distributions and the susceptibility patterns of Aspergillus species causing fungal infections in Spanish medical centers from 2000 to 2002. The susceptibilities of 338 isolates to amphotericin B, itraconazole, and voriconazole were tested. Aspergillus fumigatus was the most common species (54.7%), followed by Aspergillus terreus (14.8%) and Aspergillus flavus (13.9%). Non-A. fumigatus species were encountered in 45.3% of the samples studied. The majority of Aspergillus isolates were obtained from respiratory tract specimens, followed by ear and skin samples. The geometric mean (GM) MIC of amphotericin B was 0.56 μg/ml, and the amphotericin B MIC was >2 μg/ml for 16 isolates (4.7%). Nine of them were A. terreus. The GM MIC of itraconazole was 0.37, and the itraconazole MIC was >4 μg/ml for 12 (3.5%) isolates. The voriconazole MICs were also high for 8 of the 12 strains for which itraconazole MICs were high (voriconazole MIC range, 2 to 8 μg/ml).

scholarly journals Antifungal Susceptibility of Non-albicans Candida Species in A Tertiary Care Hospital, Bulgaria

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Hristina Yotova Hitkova ◽  
Diana Simeonova Georgieva ◽  
Preslava Mihailova Hristova ◽  
Teodora Vasileva Marinova-Bulgaranova ◽  
Biser Kirilov Borisov ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Tertiary Care ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Care Hospital ◽  
And Control

Background: Emerging non-albicans Candida (NAC) species are a major threat because of their intrinsic or acquired resistance to routinely applied antifungal agents. Objectives: The purpose of our study was to reveal in vitro activity of nine antifungal agents against NAC isolates. Methods: A total of 67 NAC (27 Candida glabrata, 10 C. tropicalis, 6 C. krusei, 6 C. parapsilosis, 4 C. lusitaniae, 4 C. lipolytica, etc.) were identified and tested. The antifungal susceptibility was estimated on the basis of minimum inhibitory concentrations (MIC). Results: Overall, 13 species were determined, of which C. glabrata was the most common (40.3%), followed by C. tropicalis (14.9%), C. krusei, and C. parapsilosis (8.9 % each). Forty-nine NAC isolates (73.13%) demonstrated decreased susceptibility to one or more antifungals, and 18 of them were resistant to all azoles. Out of 27 C. glabrata, 12 (44.4%) were resistant to fluconazole with MICs: 32 - >128 µg/mL and 15 (55.6%) were intermediate with MICs: 8 - 16 µg/mL Non-albicans Candida revealed a good susceptibility to echinocandins. Amphotericin B resistance was found in 5.97% of the isolates. Of particular interest was the detection of 6 (8.95%) multidrug-resistant NAC, which expressed resistance to azoles and echinocandins and/or amphotericin B. Conclusions: About one-fourth of the studied NAC were resistant to all azoles. These findings as well as the detection of several multidrug-resistant isolates determine the necessity of susceptibility testing of clinically important yeast isolates and control of the antifungal drugs in our hospital.

scholarly journals Structure-In Vitro Activity Relationships of Pentamidine Analogues and Dication-Substituted Bis-Benzimidazoles as New Antifungal Agents

1998 ◽  
Vol 42 (10) ◽  
pp. 2495-2502 ◽  
Author(s):  
Maurizio Del Poeta ◽  
Wiley A. Schell ◽  
Christine C. Dykstra ◽  
Susan Jones ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Fungicidal Activity ◽  
Antifungal Agents ◽  
In Vitro Activity ◽  
Primary Metabolites ◽  
Structure Activity ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Clinical Potential

ABSTRACT Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of ≤0.09 μg/ml, and the most potent compound against C. neoformans had an MIC80 of 0.19 μg/ml. Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.

scholarly journals Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents

2003 ◽  
Vol 47 (8) ◽  
pp. 2404-2412 ◽  
Author(s):  
Dominique Sanglard ◽  
Françoise Ischer ◽  
Tania Parkinson ◽  
Derek Falconer ◽  
Jacques Bille
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Wild Type ◽  
Gene Encoding ◽  
Aerobic Conditions ◽  
Targeted Deletion ◽  
Resistant Strains

ABSTRACT The role of sterol mutations in the resistance of Candida albicans to antifungal agents has not been thoroughly investigated. Previous work reported that clinical C. albicans strains resistant to both azole antifungals and amphotericin B were defective in ERG3, a gene encoding sterol Δ5,6-desaturase. It is also believed that a deletion of the lanosterol 14α-demethylase gene, ERG11, is possible only under aerobic conditions when ERG3 is not functional. We tested these hypotheses by creating mutants by targeted deletion of the ERG3 and ERG11 genes and subjecting those mutants to antifungal susceptibility testing and sterol analysis. The homozygous erg3/erg3 mutant created, DSY1751, was resistant to azole derivatives, as expected. This mutant was, however, slightly more susceptible to amphotericin B than the parent wild type. It was possible to generate erg11/erg11 mutants in the DSY1751 background but also, surprisingly, in the background of a wild-type isolate with functional ERG3 alleles under aerobic conditions. This mutant (DSY1769) was obtained by exposure of an ERG11/erg11 heterozygous strain in a medium containing 10 μg of amphotericin B per ml. Amphotericin B-resistant strains were obtained only from ERG11/erg11 heterozygotes at a frequency of approximately 5 × 10−5 to 7 × 10−5, which was consistent with mitotic recombination between the first disrupted erg11 allele and the other remaining functional ERG11 allele. DSY1769 was also resistant to azole derivatives. The main sterol fraction in DSY1769 contained lanosterol and eburicol. These studies showed that erg11/erg11 mutants of a C. albicans strain harboring a defective erg11 allele can be obtained in vitro in the presence of amphotericin B. Amphotericin B-resistant strains could therefore be selected by similar mechanisms during antifungal therapy.

scholarly journals In Vitro Activities of Ravuconazole and Four Other Antifungal Agents against Fluconazole-Resistant or -Susceptible Clinical Yeast Isolates

2004 ◽  
Vol 48 (8) ◽  
pp. 3107-3111 ◽  
Author(s):  
Manuel Cuenca-Estrella ◽  
Alicia Gomez-Lopez ◽  
Emilia Mellado ◽  
Guillermo Garcia-Effron ◽  
Juan L. Rodriguez-Tudela
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Tropicalis ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT The activities of ravuconazole and four other antifungal agents were tested against a collection of 1,796 clinical yeast isolates, including fluconazole-susceptible and -resistant strains. Ravuconazole was active against the majority of fluconazole-resistant isolates; but for 102 of 562 (18%) resistant isolates, mainly Candida tropicalis, Candida glabrata, and Cryptococcus neoformans, ravuconazole MICs were ≥1 μg/ml.

scholarly journals Species-Specific Sensitivity of Coagulase-Negative Staphylococci to Single Antibiotics and Their Combinations

2011 ◽  
Vol 60 (2) ◽  
pp. 155-161 ◽  
Author(s):  
GRAŻYNA SZYMAŃSKA ◽  
MAGDALENA SZEMRAJ ◽  
ELIGIA M. SZEWCZYK
Keyword(s):  
University Hospital ◽  
Hospital Environment ◽  
Beta Lactam ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Species Specific

The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin), vancomycin, gentamicin and rifampicin applied in vitro individually and in combination against 37 nosocomial methicillin-resistant strains of coagulase-negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of this group of bacteria and estimate the chance of the efficacy of such therapy. The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from a hospital environment and from the skin of medical staff of the intensive care unit of a paediatric ward at a university hospital. All strains were methicillin-resistant, according to CLSI standards, but individual strains differed in MIC(ox) values. Susceptibility to other tested antibiotics was also characteristic for the species. The increased susceptibility to antibiotics in combinations, tested by calculating the fractional inhibitory concentration (FIC) index, concerned 26 out of 37 investigated strains and it was a feature of a particular species. Combinations of vancomycin and cephalotin against S. epidermidis and oxacillin with vancomycin were significant, as well as cephalotin and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

scholarly journals Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Content Type ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Pass Through

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.

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