Pharmacology of Systemic Antifungal Agents

Ashley, Elizabeth S. Dodds; Lewis, Russell E.; Lewis, James S.; Martin, Craig A.; Andes, David R.

doi:10.1086/504492

Cited by 261 publications

(189 citation statements)

References 108 publications

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“…The latter compound is a triazole frequently prescribed to treat Candida spp. infections because of its excellent patient tolerance and minimal side effects 11 , although a number of species of Candida display fl uconazole resistance 12,13 and the growing worldwide use of this drug to treat candidemia is one of the principal causes of the recent increase in the prevalence of NCAC species 14 .…”

Section: Resultsmentioning

confidence: 99%

Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

Almeida

Shinobu-Mesquita

Svidzinski

et al. 2013

Rev. Soc. Bras. Med. Trop.

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Introduction: Hospital infections caused by Candida spp. are a leading cause of morbidity and mortality in hospitalized patients, particularly those that are critically ill or immunocompromised. In this study, the distributio n of Candida species in isolates from the University Hospital of the Federal University at Grande Dourados and their in vitro susceptibility to antifungal drugs were analyzed. Methods: Yeasts were phenotypically identifi ed using classical methodologies. Antifungal susceptibility tests to amphotericin B and fl uconazole were performed using the broth microdilution technique. Results: A total of 50 Candida isolates were obtained from hospitalized patients during the study period. We analyzed yeast isolates from urine (n=31; 62%), blood (n=12; 24%), and tracheal secretions (n=7; 14%). The following Candida species were identifi ed: C. tropicalis (n=21; 42%), C. albicans (n=18; 36%), C. glabrata (n=10; 20%), and C. krusei (n=1; 2%). Antifungal susceptibility tests demonstrated that C. albicans was susceptible to both antifungal agents. However, 31.2% of the non-C. albicans Candida isolates displayed dose-dependent susceptibility to fl uconazole, and 3.1% were resistant to amphotericin B. Conclusions: In contrast to previous reports, our results indicated that C. tropicalis was the most commonly isolated yeast species among the hospital patients. The predominance of non-C. albicans Candida infections confi rms the importance of species-level identifi cation for implementing appropriate antifungal therapies.

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Section: Resultsmentioning

confidence: 99%

Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

Almeida

Shinobu-Mesquita

Svidzinski

et al. 2013

Rev. Soc. Bras. Med. Trop.

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“…It binds to ergosterol in the fungal cell membrane, resulting in pore formation and leakage of cell constituents. 28 The therapeutic advantages provided by the broad spectrum of activity, including yeasts and moulds, are offset by infusion-related toxicity and nephrotoxicity. In contrast, lipid formulations of amphotericin B maintain similar efficacy and are generally associated with fewer toxicities, but are significantly more expensive.…”

Section: Introductionmentioning

confidence: 99%

“…Amphotericin B is extensively protein bound in serum to lipoproteins via cholesterol, 30 serum albumin and human a1-acid glycoprotein, 31 but liposomal amphotericin largely remains within the liposomes in serum and hence does not appear to be significantly protein bound (Table 3). 31 The metabolic pathway of amphotericin B and liposomal amphotericin is largely unknown, 28,32 rendering assessment of the impact of genetic variation somewhat speculative. In the case of amphotericin B deoxycholate, most of the drug is excreted unchanged in urine or faeces with 490% recovered within 7 days, suggesting that little metabolic breakdown occurs.…”

Section: Introductionmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

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“…1). Amphotericin B and nystatin A 1 have serious liabilities including high toxicity and negligible oral bioavailability, and their continued use reflects the lack of better alternatives (11,12).…”

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confidence: 99%

Selvamicin, an atypical antifungal polyene from two alternative genomic contexts

Arnam

Ruzzini

Sit

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

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The bacteria harbored by fungus-growing ants produce a variety of small molecules that help maintain a complex multilateral symbiosis. In a survey of antifungal compounds from these bacteria, we discovered selvamicin, an unusual antifungal polyene macrolide, in bacterial isolates from two neighboring ant nests. Selvamicin resembles the clinically important antifungals nystatin A1 and amphotericin B, but it has several distinctive structural features: a noncationic 6-deoxymannose sugar at the canonical glycosylation site and a second sugar, an unusual 4-O-methyldigitoxose, at the opposite end of selvamicin’s shortened polyene macrolide. It also lacks some of the pharmacokinetic liabilities of the clinical agents and appears to have a different target. Whole genome sequencing revealed the putative type I polyketide gene cluster responsible for selvamicin’s biosynthesis including a subcluster of genes consistent with selvamicin’s 4-O-methyldigitoxose sugar. Although the selvamicin biosynthetic cluster is virtually identical in both bacterial producers, in one it is on the chromosome, in the other it is on a plasmid. These alternative genomic contexts illustrate the biosynthetic gene cluster mobility that underlies the diversity and distribution of chemical defenses by the specialized bacteria in this multilateral symbiosis.

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Pharmacology of Systemic Antifungal Agents

Cited by 261 publications

References 108 publications

Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Selvamicin, an atypical antifungal polyene from two alternative genomic contexts

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