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The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
OBJECTIVES
To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials comparing fluconazole with amphotericin B.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.
Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 25188769
DOI: 10.1002/14651858.CD000239.pub2 -
Journal de Mycologie Medicale Aug 2023The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like...
The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like chitosan hold unique structural properties and thus can be utilized in the synthesis of biologically important scaffolds. To address the current scenario, the author's synthesized novel chitosan-azetidine derivative by adopting one-pot multicomponent reaction approach. The influence of chemical modification on the structural characteristics was investigated by means of spectroscopic techniques viz. FT-IR and HNMR and elemental analysis. Additionally, the authors investigated the antifungal potential of chitosan-azetidine derivative against Aspergillus fumigatus 3007 and the results indicated higher antifungal effect with an antifungal inhibitory index of 26.19%. The SEM and confocal microscopy images also reflected a significant inhibitory effect on the morphology of fungal mycelia, thus reflecting the potential of synthesized chitosan-azetidine derivativeas a potential antifungal agent.
Topics: Humans; Antifungal Agents; Chitosan; Spectroscopy, Fourier Transform Infrared; COVID-19; Azetidines
PubMed: 37354816
DOI: 10.1016/j.mycmed.2023.101409 -
Bioorganic & Medicinal Chemistry Feb 2018The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents...
The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activity of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against mammalian cells. The best compounds from our study exhibited broad-spectrum activity against most of the fungal strains tested, with excellent MIC values against a number of clinical isolates. The most promising compounds were found to be less hemolytic than the least hemolytic FDA-approved azole antifungal agent voriconazole (VOR). Finally, we demonstrated that the synthetic alkyl-amino FLC analogues displayed chain-dependent fungal membrane disruption as well as inhibition of ergosterol biosynthesis as possible mechanisms of action.
Topics: Animals; Antifungal Agents; Candida; Cell Line; Cell Survival; Drug Design; Erythrocytes; Fluconazole; Fungi; Hemolysis; Mice; Microbial Sensitivity Tests; Structure-Activity Relationship; Voriconazole
PubMed: 29279242
DOI: 10.1016/j.bmc.2017.12.018 -
International Journal of Biological... Mar 2018The pomegranate (Punica granatum) sarcotesta contains a chitin-binding lectin (PgTeL) with antibacterial activity against human pathogenic species. In this work, the...
The pomegranate (Punica granatum) sarcotesta contains a chitin-binding lectin (PgTeL) with antibacterial activity against human pathogenic species. In this work, the structural stability of PgTeL was evaluated by fluorimetric analysis and the lectin was evaluated for cytotoxicity to human peripheral blood mononuclear cells (PBMCs) and antifungal activity against Candida albicans and Candida krusei. PgTeL folding was impaired when lectin was incubated at pH≥6.0. On the other hand, the lectin did not undergo unfolding even when heated at 100°C. PgTeL (1, 10, and 100μg/mL) was not cytotoxic to PBMCs. Antifungal activity was detected for C. albicans (MIC: 25μg/mL; MFC: 50μg/mL) and C. krusei (MIC and MFC of 12.5μg/mL). Treatment of yeast cells with PgTeL resulted in decrease of intracellular ATP content even at sub-inhibitory concentrations (½MIC and ¼MIC) and induced lipid peroxidation. In addition, PgTeL damaged the integrity of fungal cell wall of both species, with more pronounced effects in C. krusei. The lectin showed significant antibiofilm activity on C. albicans at sub-inhibitory concentrations (0.195 and 0.39μg/mL). In conclusion, PgTeL is an anti-Candida agent whose action mechanism involves oxidative stress, energetic collapse, damage to the cell wall and rupture of yeast cells.
Topics: Antifungal Agents; Biofilms; Candida; Candida albicans; Cell Wall; Humans; Hydrogen-Ion Concentration; Lectins; Lipid Peroxidation; Lythraceae; Microbial Sensitivity Tests; Temperature
PubMed: 29225175
DOI: 10.1016/j.ijbiomac.2017.12.039 -
Frontiers in Cellular and Infection... 2021As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, emerged as a major health...
As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to . in EUH in 2019-2020. isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and and HS1/HS2- were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS . isolates were recovered from 53% of the patients admitted to EUH in 2019-2020. Y132F was the most frequent mutation in Erg11. All patients infected with . isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% . 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F . , which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.
Topics: Antifungal Agents; Candida parapsilosis; Candidemia; Child; Disease Outbreaks; Drug Resistance, Fungal; Fluconazole; Humans; Microbial Sensitivity Tests; Turkey
PubMed: 33968809
DOI: 10.3389/fcimb.2021.676177 -
American Family Physician May 2002Tinea infections are superficial fungal infections caused by three species of fungi collectively known as dermatophytes. Commonly these infections are named for the body... (Review)
Review
Tinea infections are superficial fungal infections caused by three species of fungi collectively known as dermatophytes. Commonly these infections are named for the body part affected, including tinea corporis (general skin), tinea cruris (groin), and tinea pedis (feet). Accurate diagnosis is necessary for effective treatment. Diagnosis is usually based on history and clinical appearance plus direct microscopy of a potassium hydroxide preparation. Culture or histologic examination is rarely required for diagnosis. Treatment requires attention to exacerbating factors such as skin moisture and choosing an appropriate antifungal agent. Topical therapy is generally successful unless the infection covers an extensive area or is resistant to initial therapy. In these cases, systemic therapy may be required. Tinea corporis and cruris infections are usually treated for two weeks, while tinea pedis is treated for four weeks with an azole or for one to two weeks with allylamine medication. Treatment should continue for at least one week after clinical clearing of infection. Newer medications require fewer applications and a shorter duration of use. The presence of inflammation may necessitate the use of an agent with inherent anti-inflammatory properties or the use of a combination antifungal/steroid agent. The latter agents should be used with caution because of their potential for causing atrophy and other steroid-associated complications.
Topics: Administration, Topical; Antifungal Agents; Betamethasone; Clotrimazole; Drug Combinations; Humans; Tinea
PubMed: 12046779
DOI: No ID Found -
JPMA. the Journal of the Pakistan... Jul 2022To examine the in vitro antifungal effects of water-soluble pure elemental boron with an alkaline solution against Candida species, Trichophyton species, and Aspergillus...
OBJECTIVE
To examine the in vitro antifungal effects of water-soluble pure elemental boron with an alkaline solution against Candida species, Trichophyton species, and Aspergillus fumigatus that cause superficial mycosis.
METHODS
The study was conducted at the microbiology laboratory of Kahramanmaras Sutcu Imam University Hospital, Kahramanmaras, Turkey, from June to December 2018, and comprised fungal strains isolated from patients with superficial mycosis who visited the dermatology clinic. The in vitro antifungal effects of the boron solution at various concentrations were determined using the microbroth dilution method. Candida albicans ATTC 90028 and Candida albicans MYA 274 served as the quality control strains, while fluconazole and amphotericin B were used as comparator antifungal agents. Data was analysed using SPSS 22.
RESULTS
Of the 58 strains, 28(48.3%) were Candida albicans, 9(15.5%) non-Candida albicans, 12(20.7%) Trichophyton rubrum, 4(6.9%) Trichophyton mentagrophytes, 2(3.4%) Trichophyton species and 3(5.2%) were Aspergillus fumigates. Boron at a concentration of 78.125 μg/mL inhibited the growth of Candida albicans. The 50% and 90% minimum inhibitory concentrations of the solution in non-Candida albicanswere 78.125 and 312.5 μg/mL, respectively, whereas those in Trichophyton rubrum were 312.5 and 625 μg/mL, respectively. The 50% minimum inhibitory concentration of the solution in Aspergillus fumigatus was 625 μg/mL, whereas the 90% minimum inhibitory concentration could not be determined.
CONCLUSIONS
Boron is an inexpensive, non-antibiotic element with potential uses as an antifungal agent.
Topics: Amphotericin B; Antifungal Agents; Arthrodermataceae; Boron; Candida; Candida albicans; Fluconazole; Humans; Microbial Sensitivity Tests; Trichophyton; Water
PubMed: 36156555
DOI: 10.47391/JPMA.2219 -
Microbiology Spectrum Dec 2023are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of virulence...
are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of virulence is the ability to form a biofilm. These structures are highly resistant to antifungal therapies and are often the cause of treatment failure. In this work, we evaluated the efficacy of the antifungal compound, occidiofungin, against biofilms developed on a silicone surface. We demonstrate that occidiofungin eliminated cells at all stages of biofilm formation in a dose-dependent manner. Consistent with our understanding of occidiofungin bioactivity, we noted alterations to actin organization and cell morphology following antifungal exposure. Given the challenges associated with the treatment of biofilm-associated infections, occidiofungin exhibits potential as a therapeutic antifungal agent in the future.
Topics: Candida; Antifungal Agents; Candida albicans; Silicone Elastomers; Biofilms; Microbial Sensitivity Tests
PubMed: 37816202
DOI: 10.1128/spectrum.02460-23 -
Antimicrobial Agents and Chemotherapy Apr 2022Aspergillus terreus is an opportunistic causative agent of invasive aspergillosis and, in most cases, it is refractory to amphotericin B (AMB) therapy. Notably,...
Aspergillus terreus is an opportunistic causative agent of invasive aspergillosis and, in most cases, it is refractory to amphotericin B (AMB) therapy. Notably, AMB-susceptible Aspergillus terreus (s.s.) representatives exist which are also associated with poor clinical outcomes. Such findings may be attributable to drug tolerance, which is not detectable by antifungal susceptibility testing. Here, we tested antifungal susceptibility (AFST) and the fungicidal activity of AMB against 100 clinical isolates of A. terreus species complex in RPMI 1640 and antibiotic medium 3 (AM3). MICs ranged from 0.5 to 16 μg/mL for RPMI 1640 and from 1 to >16 mg/L for AM3. AMB showed medium-dependent activity, with fungicidal effects only in antibiotic medium 3, not in RPMI 1640. Furthermore, the presence of AMB-tolerant phenotypes of A. terreus has been examined by assessing the minimum duration for killing 99% of the population (MDK99) and evaluating the data obtained in a Galleria mellonella infection model. A time-kill curve analysis revealed that A. terreus with AMB MICs of ≤1 mg/L (susceptible range) displayed AMB-tolerant phenotypes, exhibiting MDK99s at 18 and 36 h, respectively. Survival rates of infected G. mellonella highlighted that AMB was effective against susceptible A. terreus isolates, but not against tolerant or resistant isolates. Our analysis reveals that A. terreus isolates which are defined as susceptible based on MIC may comprise tolerant phenotypes, which may, in turn, explain the worse outcome of AMB therapy for phenotypically susceptible isolates.
Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillus; Drug Resistance, Fungal; Drug Tolerance; Microbial Sensitivity Tests
PubMed: 35254091
DOI: 10.1128/aac.02274-21 -
Journal of Applied Microbiology Sep 2014Clotrimazole is a broad-spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic,... (Review)
Review
Clotrimazole is a broad-spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic, clotrimazole is widely used as a topical treatment for tinea pedis (athlete's foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays fungistatic antimycotic activity by targeting the biosynthesis of ergosterol, thereby inhibiting fungal growth. As well as its antimycotic activity, clotrimazole has become a drug of interest against several other diseases such as sickle cell disease, malaria and some cancers. It has also been combined with other molecules, such as the metals, to produce clotrimazole complexes that show improved pharmacological efficacy. Moreover, several new, modified-release pharmaceutical formulations are also undergoing development. Clotrimazole is a very well-tolerated product with few side effects, although there is some drug resistance appearing among immunocompromised patients. Here, we review the pharmaceutical chemistry, application and pharmacology of clotrimazole and discuss future prospects for its further development as a chemotherapeutic agent.
Topics: Antifungal Agents; Clotrimazole
PubMed: 24863842
DOI: 10.1111/jam.12554