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

Pharmacokinetics of Antifungal Agents

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 380-382 ◽  
Author(s):  
A. Fabris ◽  
M. V. Pellanda ◽  
C. Gardin ◽  
A. Contestabile ◽  
R. Bolzonella
Keyword(s):  
Abdominal Pain ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Peritoneal Fluid ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Intraperitoneal Administration ◽  
Point Of View ◽  
Severe Abdominal Pain ◽  
Fungal Peritonitis

The authors have evaluated the pharmacokinetics of four antifungal agents used in the therapy of fungal peritonitis. Amphotericin B (Amph B) poorly diffuses from blood into peritoneal fluid, which Intraperitoneal administration induces severe abdominal pain. 5-Fluorocytosine (5FC) easily crosses peritoneum, but resistance may appear when the drug is used alone. Ketoconazole (K) poorly penetrates into peritoneal fluid, while Fluconazole (F), used per os or intraperitoneally, shows a good antifungal activity both in serum and In the peritoneal fluid. In conclusion, from a pharmacokinetic point of view, all the antifungal agents examined, perhaps with the exception of F, do not offer, when used alone, sufficient guarantees In curing peritonitis. Therefore, for treating fungal infections in CAPD, drug combinations such as AmphB + 5FC, K + 5FC or 5FC + F have to be used.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals Distribution and antifungal susceptibility of Candida species in patients with increased risk for fungal infections

2016 ◽  
Vol 62 (1) ◽  
pp. 65-76
Author(s):  
Gordana Mirchevska ◽  
Maja Jurhar Pavlova ◽  
Elena Trajkovska-Dokic ◽  
Zaklina Cekovska ◽  
Gordana Jankoska ◽  
...  
Keyword(s):  
Blood Culture ◽  
Amphotericin B ◽  
Critically Ill Patients ◽  
Candida Species ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Clinical Specimens ◽  
Fourth Group ◽  
Increased Risk

Candida species are opportunistic yeasts that can be a serious threat for immunocompromised and critically ill patients, and a cause for increased morbidity and mortality in hospitalized patients. The aim of this study was to determine the frequency and distribution of different Candida species in clinical specimens in patients with increased risk for fungal infections, and to determine the antifungal susceptibility profile of invasive Candida species to antifungal agents. During a two year period, clinical specimens from 120 patients divided into 4 groups were analysed at the Institute of microbiology and parasitology, Faculty of Medicine, Skopje, Republic of Macedonia. Each of these 4 groups consisted of specimens from 30 patients, with primary immune deficiency, critically ill patients treated in the intensive care units (ICU), patients with mucosal candidiasis only, and patients with cystic fibrosis. All specimens were investigated with conventional mycological methods. Identification of Candida species was performed with VITEK-2 system (bioMérieux, France). E-test strips of fluconazole, voriconazole, amphotericin B and caspofungin (AB bioMerieux, France) were used for determination of the antifungal susceptibility profile. In this study, a total of 115 isolates of Candida species were confirmed in different clinical specimens (91 isolates from mucosal surfaces and 24 isolates from blood culture). Colonisation of mucosal membranes of gastrointestinal, respiratory and/or urinary tracts was registered in 56.67% (17/30), 56.67% (17/30), 90% (27/30) and 100% (30/30) of the specimens in the first, second, third and fourth group respectively. In all four groups of patients, the following Candida species were confirmed: C. albicans - 55%, C. glabrata - 17.6%, C. parapsilosis - 7.7%, C. tropicalis - 6.6%, unidentified Candida species - 4.4%, C. dubliniensis - 3.3%, C. kefyr - 2.2%, and one isolate of C. rugosa, C. pelliculosa and C. krusei each. Positive blood culture was registered in 23.33% specimens from the first group, 43.33% in the second group, 23.08% of the third group, and in one specimen of the fourth group. The most frequent isolates from blood culture were C. tropicalis and C. krusei, followed by C. albicans, C. parapsilosis and C. tropicalis, and in the second group C. albicans and C. pelliculosa were equally distributed, followed by C. parapsilosis and C. glabrata. All invasive isolates of Candida species were susceptible to amphotericin B, voriconazole and caspofungin. Resistance to fluconazole was registered in 8.3% (2/24) of all confirmed Candida species. Dose-dependent susceptibility to fluconazole was confirmed in 46% (11/24) of the isolates. Our study confirms high prevalence of colonisation and candidemia with non-albicans Candida species. Resistance to antifungal agents was registered only in two isolates of C. krusei. An epidemiological study is necessary for surveillance of dynamics of candidemia and antifungal susceptibility profile of invasive isolates of Candida species in our patients.

Systemic Antifungal Agents

2018 ◽  
Author(s):  
Brett A Melnikoff ◽  
René P Myers
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Morbidity And Mortality ◽  
Transplant Recipients ◽  
Therapeutic Approaches ◽  
Timely Fashion ◽  
Antifungal Chemotherapy

Fungal infections remain an important cause of morbidity and mortality in surgical settings, with critically ill patients, transplant recipients, and sick neonates all especially vulnerable. Fungal infections remain an important cause of morbidity and mortality in surgical settings, with critically ill patients, transplant recipients, and sick neonates all especially vulnerable. Despite the development of a number of new and useful antifungal agents in the past decade and the noteworthy improvements in therapeutic approaches to fungal infections, physicians’ ability to diagnose these infections in a timely fashion remains limited, and patient outcomes remain poor. Antifungal prophylaxis has emerged as a potential means of reducing the occurrence of serious fungal infections. In patient populations estimated to be at high risk for acquiring a fungal infection, antifungal prophylaxis has reduced infection rates by about 50%; however, it has not been shown to significantly improve mortality. This review discusses both established and newly approved systemic antifungal agents. Tables list characteristics of currently available antifungals and antifungal chemotherapy. This review contains 2 tables and 32 references Key words: antifungal chemotherapy, antifungal prophylaxis, antifungals, Candida prophylaxis, systemic antifungal medications

scholarly journals In VitroInteractions of Antifungal Agents and Tacrolimus against Aspergillus Biofilms

2015 ◽  
Vol 59 (11) ◽  
pp. 7097-7099 ◽  
Author(s):  
Lujuan Gao ◽  
Yi Sun
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Inhibitory Activity ◽  
Aspergillus Terreus ◽  
Antifungal Agents ◽  
Broth Microdilution ◽  
Content Type ◽  
Antagonistic Effects

ABSTRACTAspergillusbiofilms were prepared fromAspergillus fumigatus,Aspergillus flavus, andAspergillus terreusvia a 96-well plate-based method, and the combined antifungal activity of tacrolimus with azoles or amphotericin B againstAspergillusbiofilms was investigated via a broth microdilution checkerboard technique system. Our results suggest that combinations of tacrolimus with voriconazole or amphotericin B have synergistic inhibitory activity againstAspergillusbiofilms. However, combinations of tacrolimus with itraconazole or posaconazole exhibit no synergistic or antagonistic effects.

Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

2020 ◽  
Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

scholarly journals Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

2018 ◽  
Vol 5 (3) ◽  
pp. 171814 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Wen Yang ◽  
Duo Li ◽  
Shunli Ji ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Water Soluble ◽  
Naphthalene Acetic Acid ◽  
Innovative Strategy ◽  
Molecular Arrangement

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans . The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

Two mutants selectively resistant to polyenes reveal distinct mechanisms of antifungal activity by nystatin and amphotericin B

2005 ◽  
Vol 33 (5) ◽  
pp. 1206-1209 ◽  
Author(s):  
I. Hapala ◽  
V. Klobučníková ◽  
K. Mazáňová ◽  
P. Kohút
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Structural Similarity ◽  
Resistant Mutant ◽  
Factors Affecting ◽  
Polyene Macrolides ◽  
Mode Of Inheritance ◽  
Nystatin Resistance

Polyene macrolides nystatin and amphotericin B are widely used in the treatment of fungal infections. In order to characterize factors affecting polyene activity, we have isolated Saccharomyces cerevisiae mutants showing selective resistance to nystatin and amphotericin B. Characterization of two of these mutants (nystatin-resistant mutant X1/16 and amphotericin B-resistant mutant X3/33) is presented. Genetic analysis revealed that resistance in each of these mutants is caused by a mutation in one gene with a different mode of inheritance. Nystatin resistance in mutant X1/16 is caused by changes in sterol spectrum while amphotericin B resistance in mutant X3/33 is probably related to modification of the cell wall. Our results suggest that, in spite of their structural similarity, nystatin and amphotericin B differ significantly in mechanisms of their antifungal activity.

Management of Candidiasis in Critically Ill Patients

2002 ◽  
Vol 15 (2) ◽  
pp. 106-113
Author(s):  
Manjunath P. Pai ◽  
Larry H. Danziger ◽  
Susan L. Pendland
Keyword(s):  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Economic Consequences ◽  
Drug Selection ◽  
Testing Method ◽  
Candida Infections

Fungal infections have been increasing at an alarming rate in critically ill patients. Candida is now the fourth most common pathogen isolated from the bloodstream and is associated with significant morbidity, mortality, and economic consequences. Novel antifungals have been developed in recent years to provide alternatives to amphotericin B, which continues to be the standard therapy for most invasive fungal infections. These alternatives include lipid-based amphotericin B, ketoconazole, fluconazole, itraconazole, caspofungin, and potentially voriconazole. Optimal therapy for the various forms of candidiasis remains controversial. A standardized antifungal susceptibility testing method for Candida isolates has been developed to assist drug selection, but its clinical relevance remains to be determined. The relative susceptibility of Candida isolates can be estimated by the species. Specifically, C krusei is resistant to azoles, C glabrata may be resistant to azoles, and C lusitaniae may be resistant to amphotericin B Candida infections can affect any organ system, and the diagnosis of such infections remains difficult. The Infectious Diseases Society of America recently developed guidelines for the management of candidiasis. This review includes a brief discussion of systemically administered antifungal agents and provides a synopsis of the practice guidelines for the management of candidiasis.

Sign in / Sign up

Export Citation Format

Share Document