Quantitative determination of fluconazole‐amphotericin B antagonism to <i>Candida albicans</i> by agar diffusion

Scheven, M.; Senf, L.

doi:10.1111/j.1439-0507.1994.tb00301.x

Cited by 14 publications

(7 citation statements)

References 2 publications

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“…In contrast, antagonism was reported when low concentrations of each agent were used against C. parapsilosis and indifference was observed when higher concentrations of both ketoconazole and flucytosine were employed (19). (107,122,154,185,186,198,214). Most of these studies have been performed using C. albicans isolates, but results with the non-albicans Candida spp.…”

Section: Neoformans (I) In Vitro Datamentioning

confidence: 84%

“…Antagonism among antifungal agents might occur in one of several ways. (i) Direct antifungal action at the same site results in decreased ability of other agents to exert their competitive effects on that site or at an altered target, as proposed for the azoles and amphotericin B (31,49,182,183,185,186,203). Azoles block the synthesis of ergosterol in the fungal cell membrane and may thus render amphotericin B inactive, since this agent exerts its activity by binding to ergosterol in the cell membrane.…”

Section: Mechanisms Of Interactions For the Antifungal Agentsmentioning

confidence: 99%

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Combination Antifungal Therapy

Johnson

MacDougall

Ostrosky-Zeichner

et al. 2004

Antimicrob Agents Chemother

487

368

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5 RATIONALEThe availability of new antifungal agents with novel mechanisms of action has stimulated renewed interest in combination antifungal therapies. In particular, and despite the limited clinical data, the high mortality of mold infections and the relatively limited efficacy of current agents have produced significant interest in polyene-, extended-spectrum azole-, and echinocandin-based combinations for these difficult-to-treat infections. With the recent publication of the first large randomized trial of antifungal combination therapy to be conducted in two decades (166) and the rapid proliferation of new in vitro and in vivo data on antifungal combinations, we have sought to review the recent work and future challenges in this area.The focus of this review is on the efficacy of antifungal drugs in combination with respect to the extent or rate of killing of the fungal pathogen, although other potential interactions (such as pharmacokinetic drug interactions) can impact efficacy when these agents are used together. The value of giving two drugs because each is separately effective against a group of organisms exhibiting a variety of types of resistance is not specifically discussed, but this also is an obvious and straightforward reason to use a combination of agents.It cannot be simply assumed that the use of two or more effective drugs with different mechanisms of action will produce an improved outcome compared to the results seen with a single agent. Combination antifungal therapy could reduce antifungal killing and clinical efficacy, increase potential for drug interactions and drug toxicities, and carry a much higher cost for antifungal drug expenditures without proven clinical benefit (106). Thus, it is important to critically evaluate the role of combination therapy as new data become available.Conceptual models and terminology. Methods for studying antifungal combinations in vitro and in vivo have differed considerably over time and among investigators. These tools do not differ with respect to their application to combination antibacterial or antiviral therapies and have been discussed extensively and elegantly in the landmark 1995 review by Greco (79). In brief, all approaches to evaluating combinations can be reduced to two elements: (i) a conceptual model for predicting the expected result for a combination and (ii) a set of phrases used to categorize results that are better than expected, worse than expected, or as expected. Although many subtle variations are possible, the underlying mathematical model is based on either the assumption of additive interactions or the assumption of probabilistic (multiplicative) interactions. On the basis of the terminology employed by the author who first carefully described each of these models, the two models can be usefully referred to as the Loewe additivity model and the Bliss independence model (79).The terminology used to place results into interpretive categories is often the subject of debate and confusion. Greco et al. (79) have proposed a set ...

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Section: Neoformans (I) In Vitro Datamentioning

confidence: 84%

Section: Mechanisms Of Interactions For the Antifungal Agentsmentioning

confidence: 99%

Combination Antifungal Therapy

Johnson

MacDougall

Ostrosky-Zeichner

et al. 2004

Antimicrob Agents Chemother

487

368

View full text Add to dashboard Cite

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“…The effectiveness of treatment with the combination of amphotericin B with azole for Candida infection has not been determined and is still controversial. Fluconazole and amphotericin B have been shown to be antagonistic against C. albicans under carefully selected in vitro conditions [36]. An in vivo study by Sugar et al [37], however, did not demonstrate this antagonism against C. albicans.…”

Section: Discussionmentioning

confidence: 97%

Candida lusitaniae: A Cause of Breakthrough Fungemia in Cancer Patients

Minari

Hachem

Raad

2001

Clinical Infectious Diseases

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Candida lusitaniae is an infrequent cause of fungemia. We identified 12 cases of C. lusitaniae fungemia that occurred at the University of Texas M. D. Anderson Cancer Center from 1988 to 1999. The mean age of patients was 48 years (range 20--70 years). Eight patients had hematologic malignancy or had received a bone marrow transplant, and 4 had a solid tumor. Most patients (75%) were neutropenic (<10(3)/mm(3)). Treatment with amphotericin B alone failed for 3 of 6 patients, irrespective of neutropenic status. Fluconazole was effective as a single agent in 3 patients with solid tumors. The combination of amphotericin B plus fluconazole was effective treatment for two-thirds of patients with hematologic malignancy, despite persistence of neutropenia. The mortality rate associated with C. lusitaniae infection was 25%. C. lusitaniae presents as breakthrough fungemia in immunocompromised patients and is associated with failure of amphotericin B therapy. Fluconazole may be a useful agent in the treatment of this infection.

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“…During this time, both antagonism and synergism of the activity of AMB when fungi are pre-exposed to azoles have been observed in vivo as well as in vitro [20]. The resulting data are, however, confusing, with reports ranging from antagonism [23][24][25][26], through additive or synergistic effects [27,28], to no effect [23,29]. In clinical terms, the development of combined drug regimens and the antagonism conferred upon otherwise fungicidal concentrations of AMB seen in C. albicans pre-exposed to FLZ is disconcerting [30,31].…”

Section: Introductionmentioning

confidence: 82%

“…A quantitative agar double-diffusion method used to study this antagonism has shown that FLZ antagonizes the effect of AMB against C. albicans [24]. Another group of researchers observed that AMB and FLZ interactions with C. albicans were antagonistic [47].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Polyene-Azole Antagonism in Liquid Cultures of <i>Candida albicans</i> Using an Automated Turbidometric Method

Samaranayake¹,

Samaranayake²,

Yeung³

2001

Chemotherapy

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Background: A computerized machine, SPECTRAmax 340, was used to evaluate the recently reported phenomenon of antagonism of the polyene amphotericin B (AMB) in Candida albicans pre-exposed to the triazole fluconazole (FLZ). Methods: We investigated growth inhibition by varying concentrations of AMB in seven isolates of C. albicans pre-exposed to FLZ (50 µg/ml) for 18 h. All isolates were obtained on sequential visits from human immunodeficiency virus-infected patients not treated with FLZ. Results: Antagonism of AMB activity was observed in 5, 4, 2 and a single isolate for 0.5, 1, 2 and 3 µg/ml of the antifungal, respectively. In the majority of Candida isolates, antagonism was seen within a concentration range of 0.5–1.0 µg/ml AMB; 1 Candida strain (HK1-Sa) was resistant to 3 µg/ml AMB. Higher concentrations of AMB (>3 µg/ml) killed both the controls and FLZ-pre-exposed Candida cells. No significant differences were observed between the periods of antagonism observed for any of the sequential isolates or for any of the AMB concentrations or in the maxima of the growth curves obtained for all Candida isolates. Conclusion: We conclude that the SPECTRAmax system is a useful tool to evaluate in vitro pharmacodynamic interactions between antifungal regimens within a fluid culture system, and provides information that cannot be obtained using traditional plate assay systems.

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Quantitative determination of fluconazole‐amphotericin B antagonism to Candida albicans by agar diffusion

Cited by 14 publications

References 2 publications

Combination Antifungal Therapy

Combination Antifungal Therapy

Candida lusitaniae: A Cause of Breakthrough Fungemia in Cancer Patients

Evaluation of Polyene-Azole Antagonism in Liquid Cultures of <i>Candida albicans</i> Using an Automated Turbidometric Method

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