Interaction Between Azoles and Amphotericin B in the Treatment of Candidiasis

Scheven, M.; Scheven, Marie-Luise

doi:10.1093/clinids/20.4.1079

Cited by 14 publications

(5 citation statements)

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“…Pretreatment with fluconazole has generally resulted in the reduction of subsequent amphotericin B activity (34,67,105,107,114,153,175,216), but in some series high azole concentrations, long duration of pretreatment, or high levels of inocula were required to produce these effects (67,107,185). Other azoles have also been reported to exert antagonistic effects on amphotericin B activity (31,185,216,217), and preexposure with more-lipophilic azoles such as itraconazole has produced more profoundly negative effects in some experimental systems (184,185,217) but not in others (216). One conflicting study report has also indicated that short preexposure to amphotericin B reduced subsequent azole activity but that similar preexposure to an azole did not inhibit subsequent polyene effects (153).…”

Section: Neoformans (I) In Vitro Datamentioning

confidence: 99%

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: 99%

Combination Antifungal Therapy

Johnson

MacDougall

Ostrosky-Zeichner

et al. 2004

Antimicrob Agents Chemother

487

368

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“…As discussed by Scheven and colleagues [11,16,17], one mechanism for the antagonism of amphotericin B and itraconazole may be that the lipophilic itraconazole blocks the interaction of amphotericin B binding to the fungal cell membrane. This would explain differences seen with itraconazole and flu- …”

Section: Concomitant Therapy With Amphotericin B and Itraconazolementioning

confidence: 99%

Interactions of Itraconazole with Amphotericin B in the Treatment of Murine Invasive Candidiasis

Sugar

Liu

1998

J INFECT DIS

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The interactions of amphotericin B and itraconazole were studied in murine invasive candidiasis. Candida albicans-infected mice were treated for 10 consecutive days, 24 h after infection. Survival was monitored over 30 days and kidney cultures were done. Mice treated with amphotericin B (0.2 mg/kg/day intraperitoneally) or itraconazole (100 mg/kg/day by oral gavage in two divided doses/ day) had a 30-day survival of 20% or 40%. Concomitant administration of both drugs resulted in 100% mortality; 90% of mice treated with amphotericin B (1 mg/kg/day) survived. With the combination, 100% were dead by day 28 (P < or = .001 vs. amphotericin B). With sequential therapy (i.e., 5 days with one drug and then 5 days with the other), survival was inferior to that with amphotericin B alone but similar to that with itraconazole alone. Kidney culture results confirmed the antagonism of the combination compared with amphotericin B alone. In treatment of murine invasive candidiasis, the concomitant or sequential use of amphotericin B and itraconazole results in a negative interaction.

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“…Earlier studies reported IHC work using in-lab-developed antibodies to detect sub-types of denatured collagen in rat articular cartilage, rat long bone, and equine articular cartilage; however, these antibodies have not been widely available. [18][19][20][21][22][23] When lacking detailed information regarding collagen integrity at the microscopic and molecular level, it is impossible to accurately assess the functional efficacy of any newly developed reparative and regenerative strategies which seek to tackle intervertebral disc degeneration. Molecular detection of extracellular matrix components, such as collagen, within the intervertebral disc not only plays a significant role in understanding disc biology and pathology but also possesses an indispensable role as a stand-alone methodology study to meet such needs in current disc research.…”

Section: Introductionmentioning

confidence: 99%

Molecular Detection and Assessment of Intervertebral Disc Degeneration via a Collagen Hybridizing Peptide

Xiao

Majumdar

Dai

et al. 2019

ACS Biomater. Sci. Eng.

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During aging, wear, and tear of intervertebral discs, human discs undergo a series of morphological and biochemical changes. Degradation of extracellular matrix proteins, e.g., collagen, arises as an important contributor and accelerator in this process. Existing methods to detect collagen degradation at the tissue level include histology and immunohistochemistry. Unfortunately, most of these methods only depict overall collagen content without the ability to specifically discern degraded collagen and to assess the severity of degeneration. To fill this technological gap, we developed a robust and simple approach to detect and assess early disc degeneration with a collagen hybridizing peptide (CHP) that hybridizes with the flawed triple

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Interaction Between Azoles and Amphotericin B in the Treatment of Candidiasis

Cited by 14 publications

References 0 publications

Combination Antifungal Therapy

Combination Antifungal Therapy

Interactions of Itraconazole with Amphotericin B in the Treatment of Murine Invasive Candidiasis

Molecular Detection and Assessment of Intervertebral Disc Degeneration via a Collagen Hybridizing Peptide

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