Anybody tried Caspofungin (Cancidas) plus FMT??? by muravey ..... Candida & Dysbiosis Forum
Date: 7/24/2015 6:04:59 AM ( 6 years ago ago)
I want to do at home IV Caspofungin during 30 days against candida+ FMT.
Here is list what i tried before and nothing works for me:
IV H202 + orally 35% - 0 result
IV Sodium Bicarbonate 8,4% (Baking Soda) - help me for a couple hours after all symptoms come back. Tried 5 IV.
IV Vitamin C- 0 result.
Iodine little help me.
Every day i in bed ,very bad condition. Without an immune deficiency.
Next step is a caspofungin+FMT
Any tips will be appreciate.
MECHANISM OF ACTION — The mechanism of action of the echinocandins exploits a biochemical pathway unique to fungi, which is different from the mechanisms of other antifungal drugs. Echinocandins target fungal cell glucan synthesis by competitively inhibiting the beta-1,3-D-glucan synthase enzyme complex in susceptible fungi (figure 2) . This enzyme complex is composed of at least two components: catalytic subunits called Fks1p and Fks2p, and a GTP-binding protein, Rho1, which regulate the activity of glucan synthesis. Beta-glucans, when cross-linked to chitin and mannoproteins, provide structural integrity to cell walls of various pathogenic fungi and molds including Candida spp, Aspergillus spp, and Pneumocystis jirovecii.
Beta-glucans account for approximately 30 to 60 percent of the cell wall mass in yeasts such as Candida species [7,8]. Beta-glucan depletion causes loss of resistance to osmotic forces and cell lysis among Candida spp, thereby having a fungicidal effect. In filamentous fungi, such as Aspergillus fumigatus, the bulk of beta-glucan synthesis is concentrated at the apical tips and branching points of hyphae [9-11]. Among filamentous fungi, echinocandin-induced beta-glucan depletion causes impeded growth at the tips and branching points of hyphae, resulting in dysmorphic hyphae; this growth inhibition has a fungistatic effect .
Beta-glucans and the intracellular beta-glucan synthase complex blocked by echinocandins are not present in human cells. For this reason, the echinocandins cause less toxicity than amphotericin B formulations or the triazoles and are implicated in fewer drug-drug interactions. In addition, the mechanism of action of the echinocandins appears to complement the antifungal effects of the other antifungal drug classes, offering the potential for combination therapy. (See "Treatment and prevention of invasive aspergillosis", section on 'Combination therapy'.)
Echinocandins may also amplify host immune responses by unmasking beta-glucan epitopes, which are highly antigenic, thereby accelerating host cellular recognition and inflammatory responses [13-17]. However, the evidence supporting such immunomodulatory effects is limited to in vitro studies and murine models.
MICROBIOLOGIC ACTIVITY — Given the widespread distribution of beta-glucans in the fungal cell wall and the high degree of homology of FKS genes among diverse fungal genera, echinocandins would be predicted to exhibit activity against a wide spectrum of fungal pathogens. However, the echinocandins are primarily effective against Candida and Aspergillus species, with relatively weak activity against other molds and yeasts, including Cryptococcus neoformans . Differences in fungal cell wall construction may influence echinocandin penetration or render some fungal species less susceptible to the effects of beta-glucan synthesis inhibition .
Candida species — All three of the echinocandins exhibit excellent potency against Candida spp (table 1) . C. albicans, C. glabrata, and C. tropicalis are highly susceptible to all three agents, whereas elevated minimum inhibitory concentrations (MICs) have been seen for C. parapsilosis and C. guilliermondii (table 2) [18,19]. Acquired resistance to the echinocandins remains sporadic [20,21] but has been documented for individual cases of infection with C. albicans, C. glabrata, C. lusitaniae, C. tropicalis, and C. parapsilosis [21-27].
Of note, there is increasing concern that some C. glabrata bloodstream isolates with resistance to fluconazole and voriconazole are also resistant to the echinocandins. In a surveillance study of the in vitro susceptibility of 1669 C. glabrata bloodstream isolates collected in the United States between 2006 and 2010, 162 isolates (9.7 percent) were resistant to fluconazole, of which 98.8 percent were also not susceptible to voriconazole (MIC >0.5 mcg/mL), and 9.3, 9.3, and 8.0 percent were resistant to anidulafungin, caspofungin, and micafungin, respectively . Of the 162 isolates that were resistant to fluconazole, 18 (11.1 percent) were resistant to one or more of the echinocandins; all of these isolates contained an FKS1 or FKS2 mutation. In comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant C. glabrata isolates tested between 2001 and 2004, years in which only one echinocandin, caspofungin, was available, and echinocandins were used sparingly. In a population-based analysis of echinocandin resistance in 1380 bloodstream isolates of C. glabrata from four United States cities collected between 2008 and 2013, 3 to 4 percent of strains were resistant to all three echinocandins, and approximately one-third of echinocandin-resistant strains were cross-resistant to fluconazole . Nearly all of the isolates with an FKS1 or FKS2 mutation were resistant to at least one echinocandin.
A 10-year study of C. glabrata bloodstream infections at a single medical center in the United States showed an increase in echinocandin resistance from 4.9 percent in 2001 to 12.3 percent in 2010 . This resistance was confirmed by the presence of FKS mutations; strains categorized as susceptible did not possess acquired mutations. On multivariate analysis, echinocandin resistance was associated with prior exposure to an echinocandin. Among 118 episodes of C. glabrata infection in which the infecting strain was categorized as susceptible using the clinical breakpoints, 109 (92.4 percent) had successful outcomes at day 10 of treatment with micafungin. Conversely, among 13 episodes of C. glabrata infection in which the strain was categorized as resistant using the clinical breakpoints and treated with micafungin monotherapy, 5 (38.5 percent) did not respond or responded initially but relapsed or recurred. Among 78 fluconazole-resistant isolates, 11 (14.1 percent) were resistant to one or more echinocandins and 8 (10.3 percent) were resistant to all echinocandins.
These findings argue for continued surveillance for resistance using standardized antifungal susceptibility testing. (See "Treatment of candidemia and invasive candidiasis in adults", section on 'Susceptibility patterns' and "Antifungal susceptibility testing", section on 'Echinocandins'.)
Candida biofilms — Echinocandins are unique among the systemic antifungal agents in their activity against biofilm-embedded Candida species. Under sessile biofilm-like conditions, the MICs for amphotericin B and fluconazole may increase by 10- to 1000-fold [30,31]. Biofilm growth in C. albicans is associated with increased secretion of carbohydrates, including beta-1,3-D-glucan , which has been shown to directly inhibit the activity of both fluconazole and amphotericin B [33-35]. In contrast, echinocandin MICs are minimally affected when tested in biofilm versus non-biofilm conditions, and a biofilm-embedded inoculum of C. albicans can be reduced by >99 percent at the echinocandin concentrations achieved in vivo [30,31].
These in vitro data suggest that echinocandins may be particularly useful antifungal agents for prosthetic device or catheter-associated infections in which biofilm-embedded organisms can be associated with recurrent candidemia. However, this remains to be proven in clinical studies.
Other yeasts — Echinocandins lack clinically useful activity against Trichosporon spp, Cryptococcus neoformans, and Cryptococcus gattii, even though beta-1,3-D-glucan synthase from Cryptococcus spp is exquisitely sensitive to inhibition by caspofungin, and beta-1,3-D-glucan is present in the fungal cell wall . Compensatory cell wall mechanisms, melanin, and drug degradation pathways may contribute to the inherent resistance of this species to echinocandins.
Dimorphic fungi — Echinocandins have only modest activity against the mycelial phase of the dimorphic fungi, Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides spp. Echinocandins are not considered to be effective agents for therapy of dimorphic fungal infections.
Aspergillus — Growth of Aspergillus species is inhibited at very low echinocandin concentrations in vitro, with the effects predominantly observed at apical and sub-apical branching points where cell wall remodeling and beta-glucan synthase are most active [10,36]. As such, MIC endpoints for Aspergillus are determined differently for echinocandins than for other antifungals. The lowest echinocandin concentration resulting in grossly abnormal hyphal forms (small, compact, highly branched hyphae as compared with the normally elongated hyphal forms) are defined at the minimum effective concentration (MEC) . MEC ranges for most Aspergillus species fall into what would be considered the susceptible range (table 3).
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