Synergism of Amphotericin B with Other Antimicrobial Agents

1973 ◽  
Vol 78 (3) ◽  
pp. 450 ◽  
Author(s):  
JAMES W. SMITH
Keyword(s):  
Amphotericin B ◽  
Antimicrobial Agents

Voriconazole: A New Triazole Antifungal Agent

2003 ◽  
Vol 37 (3) ◽  
pp. 420-432 ◽  
Author(s):  
Margaret M Pearson ◽  
P David Rogers ◽  
John D Cleary ◽  
Stanley W Chapman
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Case Reports ◽  
Empirical Therapy ◽  
Immunocompromised Patients ◽  
In Vitro Susceptibility ◽  
Medline Search

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

scholarly journals In VitroInteractions between Aspirin and Amphotericin B against Planktonic Cells and Biofilm Cells of Candida albicans and C. parapsilosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3250-3260 ◽  
Author(s):  
Yabin Zhou ◽  
Ganggang Wang ◽  
Yutang Li ◽  
Yang Liu ◽  
Yu Song ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Positive Interactions ◽  
Antibiofilm Activity ◽  
Data Generation ◽  
Planktonic Cells ◽  
Content Type ◽  
Time Kill

ABSTRACTThe increase in drug resistance and invasion caused by biofilm formation brings enormous challenges to the management ofCandidainfection. Aspirin's antibiofilm activityin vitrowas discovered recently. The spectrophotometric method and the XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} reduction assay used for data generation make it possible to evaluate fungal biofilm growth accurately. The combined use of the most commonly used methods, the fractional inhibitory concentration index (FICI) and a newly developed method, the ΔEmodel, which uses the concentration-effect relationship over the whole concentration range instead of using the MIC index alone, makes the interpretation of results more reliable. As an attractive tool for studying the pharmacodynamics of antimicrobial agents, time-kill curves can provide detailed information about antimicrobial efficacy as a function of both time and concentration. In the present study,in vitrointeractions between aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic cells and biofilm cells ofCandida albicansandC. parapsilosiswere evaluated by the checkerboard microdilution method and the time-kill test. Synergistic and indifferent effects were found for the combination of ASA and AMB against planktonic cells, while strong synergy was found against biofilm cells analyzed by FICI. The ΔEmodel gave more consistent results with FICI. The positive interactions in concentration were also confirmed by the time-kill test. Moreover, this approach also revealed the pharmacodynamics changes of ASA and synergistic action on time. Our findings suggest a potential clinical use for combination therapy with ASA and AMB to augment activity against biofilm-associated infections.

scholarly journals A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and β-1,6-Glucan Pathway Genes

2006 ◽  
Vol 50 (11) ◽  
pp. 3708-3716 ◽  
Author(s):  
Prasanna D. Khot ◽  
Peter A. Suci ◽  
R. Lance Miller ◽  
Raoul D. Nelson ◽  
Bonnie J. Tyler
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Transcript Abundance ◽  
Differential Regulation ◽  
Morphological Heterogeneity ◽  
Tubular Flow ◽  
High Level ◽  
Candida Albicans Biofilms ◽  
Small Subpopulation

ABSTRACT The resistance of Candida albicans biofilms to a broad spectrum of antimicrobial agents has been well documented. Biofilms are known to be heterogeneous, consisting of microenvironments that may induce formation of resistant subpopulations. In this study we characterized one such subpopulation. C. albicans biofilms were cultured in a tubular flow cell (TF) for 36 h. The relatively large shear forces imposed by draining the TF removed most of the biofilm, which consisted of a tangled mass of filamentous forms with associated clusters of yeast forms. This portion of the biofilm exhibited the classic architecture and morphological heterogeneity of a C. albicans biofilm and was only slightly more resistant than either exponential- or stationary-phase planktonic cells. A submonolayer fraction of blastospores that remained on the substratum was resistant to 10 times the amphotericin B dose that eliminated the activity of the planktonic populations. A comparison between planktonic and biofilm populations of transcript abundance for genes coding for enzymes in the ergosterol (ERG1, -3, -5, -6, -9, -11, and -25) and β-1,6-glucan (SKN and KRE1, -5, -6, and -9) pathways was performed by quantitative RT-PCR. The results indicate a possible association between the high level of resistance exhibited by the blastospore subpopulation and differential regulation of ERG1, ERG25, SKN1, and KRE1. We hypothesize that the resistance originates from a synergistic effect involving changes in both the cell membrane and the cell wall.

scholarly journals In Vitro Susceptibilities of Zygomycetes to Combinations of Antimicrobial Agents

2002 ◽  
Vol 46 (8) ◽  
pp. 2708-2711 ◽  
Author(s):  
Eric Dannaoui ◽  
Javier Afeltra ◽  
Jacques F. G. M. Meis ◽  
Paul E. Verweij
Keyword(s):  
Amphotericin B ◽  
Antimicrobial Agents

ABSTRACT Combinations of antimicrobial agents were tested against 35 strains of zygomycetes. The interaction between amphotericin B and rifampin was synergistic or additive. Flucytosine alone was inactive and, upon combination with amphotericin B, synergy was not achieved. The combination of amphotericin B with terbinafine was synergistic for 20% of strains, and the interaction between terbinafine and voriconazole was synergistic for 44% of strains. Antagonism was not observed.

scholarly journals Patients with Long-Term Oral Carriage Harbor High-Persister Mutants of Candida albicans

2009 ◽  
Vol 54 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Michael D. LaFleur ◽  
Qingguo Qi ◽  
Kim Lewis
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Oral Candidiasis ◽  
Wild Type ◽  
Persister Cells ◽  
Microtiter Plates ◽  
High Concentrations

ABSTRACT Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections.

scholarly journals Amphotericin B, the Wonder of Today’s Pharmacology Science: Persisting Usage for More Than Seven Decades

2020 ◽  
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Antifungal Drugs ◽  
Systemic Fungal Infection

Background: Despite several available topical and systemic antifungal drugs for the treatment of fungal infections, Amphotericin B (AmB) is still one of the most common first-line choices in treating systemic fungal infection for more than seven decades after its discovery.  Objectives: Amphotericin B which belongs to the polyene group has a wide spectrum of in vitro and in vivo antifungal activity. Its mechanism of antifungal action is characterized by creating a pore in the fungal plasma membrane leading to cell death. Methods: In addition to the old formula of deoxycholate-Amphotericin B (D-AmB), three lipid formulas have been developed to reduce the adverse effects of conventional AmB (D-AmB) in the human body and increase its therapeutic efficacy. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary research. Numerous pharmaceutical formulas of systemic and topical applications with clinical uses of AmB in just humans, not in vitro or animals model, against various fungal infections are discussed in this review. Topical AmB formulas are a promising way to develop effective management and to reduce the adverse effects of intravenous formulas of AmB without laboratory monitoring. Results: The wonderful pharmacological properties of AmB with its prolonged use for about seven decades may help researchers to apply its unique features on other various antimicrobial agents by more understanding about the AmB mechanisms of actions. Conclusion: Amphotericin B is widely used intravenously for the treatment of systemic fungal infection, while the topical formula of AmB is still under experimental study. 

Haloprogin: mode of action studies in Candida albicans

1974 ◽  
Vol 20 (9) ◽  
pp. 1241-1245 ◽  
Author(s):  
E. F. Harrison ◽  
W. A. Zygmunt
Keyword(s):  
Candida Albicans ◽  
Cell Membrane ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Fungicidal Activity ◽  
Acid Synthesis ◽  
Leucine Incorporation ◽  
Potassium Ions ◽  
Oxygen Utilization ◽  
Polyene Antibiotics

The relative antifungal properties of haloprogin, a new synthetic antimicrobial agent, and two polyene antibiotics, amphotericin B and nystatin, were determined in Candida albicans. The specific parameters studied included possible effects on (i) cell viability, (ii) oxygen utilization, (iii) uptake and incorporation of labelled leucine and uridine, and (iv) loss of intracellular K+ ions. Susceptibility of mammalian erythrocytes to lysis by these antimicrobial agents was also determined. Fungicidal activity of haloprogin appears to be attributable to inhibition of oxygen uptake and disruption of the cell membrane. Haloprogin affects protein and nucleic acid synthesis to a lesser degree as evidenced by uptake and incorporation of labelled precursors. The two polyene antibiotics act in a different manner; nystatin effectively inhibits oxygen utilization and incorporation of leucine and uridine, whereas amphotericin B affects primarily leucine incorporation. Both polyene drugs disturb the cell membrane as shown by intracellular loss of potassium ions from C. albicans cells and lysis of mammalian erythrocytes.

scholarly journals Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins

2002 ◽  
Vol 46 (6) ◽  
pp. 1773-1780 ◽  
Author(s):  
D. M. Kuhn ◽  
T. George ◽  
J. Chandra ◽  
P. K. Mukherjee ◽  
M. A. Ghannoum
Keyword(s):  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Cell Structure ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Confocal Scanning Laser Microscopy ◽  
Microbial Infection ◽  
Lipid Complex ◽  
Morphological Alterations ◽  
Lipid Formulations

ABSTRACT Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.

Treatment of Aspergillosis with Itraconazole

1993 ◽  
Vol 27 (10) ◽  
pp. 1206-1211 ◽  
Author(s):  
Timothy S. Jennings ◽  
Thomas C. Hardin
Keyword(s):  
Clinical Trials ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Oral Therapy ◽  
Antimicrobial Agents ◽  
Hematologic Malignancy ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Severe Toxicity ◽  
Primary Therapy ◽  
Open Label

OBJECTIVE: To review the role of itraconazole as oral therapy for the major infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis. DATA SOURCES: A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed. STUDY SELECTION: Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy. DATA SYNTHESIS: Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising. CONCLUSIONS: Although itraconazole offers promise for oral therapy against infections caused by Aspergillus spp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5–4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.

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