Post‐antibiotic effect and post‐expositional polyene antagonism of azole antifungal agents in <i>Candida albicans:</i> dependence on substance lipophilia

Scheven, M.; Scheven, C.; Hahn, Katherine; Senf, A.

doi:10.1111/j.1439-0507.1995.tb00016.x

Cited by 13 publications

(14 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(ii) Adsorption to the cell surface by one agent inhibits binding of another antifungal agent to its target site of activity. This mechanism is proposed for lipophilic azoles (such as itraconazole and ketoconazole) which may adsorb to the fungal cell surface and inhibit binding of amphotericin B to fungal cell membrane sterols (183,185). (iii) Modification of a target upon exposure to an antifungal agent occurs that renders the pathogen less susceptible to the effects of other antifungals.…”

Section: Mechanisms Of Interactions For the Antifungal Agentsmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

Combination Antifungal Therapy

Johnson

MacDougall

Ostrosky-Zeichner

et al. 2004

Antimicrob Agents Chemother

487

368

View full text Add to dashboard Cite

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 ...

show abstract

Section: Mechanisms Of Interactions For the Antifungal Agentsmentioning

confidence: 99%

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

show abstract

“…Second, AMB may not have been effectively removed by dilution when the cells were plated (29). AMB is more likely to remain bound to the cell membrane of C. albicans after plating of the cells than to diffuse into the plate medium buffer.…”

Section: Vol 47 2003 Resuscitation and Killing Of Amb-treated C Almentioning

confidence: 99%

“…AMB is more likely to remain bound to the cell membrane of C. albicans after plating of the cells than to diffuse into the plate medium buffer. For the azoles it is well established that their postantifungal effects and lipophilic nature are correlated (29), and the nonlipophilic fluconazole is the only azole that lacks a postantifungal effect (15,29).…”

Section: Vol 47 2003 Resuscitation and Killing Of Amb-treated C Almentioning

confidence: 99%

Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment

Liao

Rennie

Talbot

2003

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Amphotericin B treatment was previously shown to inhibit Candida albicans reproduction and reduce the fluorescence of vitality-specific dyes without causing a corresponding increase in the fluorescence of the mortality-specific dyes bis-(1,3-dibutylbarbituric acid)trimethine oxonol and SYBR Green ⌱. In the present study, we have confirmed these results and have shown that the numbers of CFU are reduced by 99.9% by treatment with 0.5 g of amphotericin B per ml for 10 h at 35°C. This reduction was not due to fungal cell death. First, the level of reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide increased in the presence of concentrations of amphotericin B that caused greater than 90% reductions in the numbers of CFU. Second, fungal cells treated with amphotericin B at a concentration of 0.5 g/ml were resuscitated by further incubation at 22°C for 15 h in the continued presence of amphotericin B. Third, recovery of the ability to replicate was prevented by sequential treatment with 20 g of miconazole per ml, which also increased the fluorescence of mortality-specific dyes to near the maximal levels achieved with 0.9 g of amphotericin B per ml. Sequential treatment with fluconazole and flucytosine did not increase the levels of staining with the mortality-specific dyes. Itraconazole was less effective than ketoconazole, which was less effective than miconazole. The practice of equating the loss of the capacity of C. albicans to form colonies with fungal cell death may give incorrect results in assays with amphotericin B, and the results of assays with caution with other antifungal agents that are lipophilic or that possess significant postantifungal effects may need to be interpreted.Candida is the fourth most common cause of nosocomial bloodstream infections in the United States (10), and the rate of primary bloodstream infections continues to increase (3). The most frequently isolated Candida species in these infections is Candida albicans. Candidemia is also frequently refractory to therapy, and the rate of mortality attributable to candidemia has been estimated to be 38% (36). Despite recent advances in the development of antifungal agents, amphotericin B (AMB) still remains the drug of choice for the treatment of life-threatening systemic infections (14), and the activity of AMB is the standard to which the activities of other antifungal agents are compared. AMB binds with the sterol ergosterol, resulting in the loss of membrane integrity and osmotic stability (5).The process of cell replication deactivation is believed to involve stepwise changes in the physiological state of a cell that render an intermediate form that is incapable of initiating replicative processes but that is still capable of metabolism (21, 27). Thus, the loss of replication competency is an early event in a phase of decline that eventually leads to cell death (19,27).We have previously examined the effects of AMB on the vitality and mortality of C. albicans cell...

show abstract

“…Moreover, several investigators have found synergistic interactions by simultaneous exposure of C. albicans to azoles and AmB (13,30). One group, on the other hand, described antagonisms with preexposures of Candida to the more lipophilic azoles, such as itraconazole, but not to fluconazole (31,32).…”

mentioning

confidence: 99%

Stable Phenotypic Resistance of Candida Species to Amphotericin B Conferred by Preexposure to Subinhibitory Levels of Azoles.

&NA;

1999

The Pediatric Infectious Disease Journal

View full text Add to dashboard Cite

The fungicidal activity of amphotericin B (AmB) was quantitated for several Candida species. Candida albicans and C. tropicalis were consistently susceptible to AmB, with less than 1% survivors after 6 h of exposure to AmB. C. parapsilosis and variants of C. lusitaniae and C. guilliermondii were the most resistant, demonstrating 50 to 90% survivors in this time period and as high as 1% survival after a 24-h exposure time. All Candida species were killed (<1% survivors) after 24 h of exposure to AmB. In contrast, overnight exposure to either fluconazole or itraconazole resulted in pronounced increases in resistance to subsequent exposures to AmB.

show abstract

Post‐antibiotic effect and post‐expositional polyene antagonism of azole antifungal agents in Candida albicans: dependence on substance lipophilia

Cited by 13 publications

References 9 publications

Combination Antifungal Therapy

Combination Antifungal Therapy

Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment

Stable Phenotypic Resistance of Candida Species to Amphotericin B Conferred by Preexposure to Subinhibitory Levels of Azoles.

Contact Info

Product

Resources

About