Protection of<i>Pythium</i>Species Against Antibacterial Antibiotics by Cholesterol

Rawn, Carroll D.

doi:10.1094/phyto-77-319

Cited by 8 publications

(6 citation statements)

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“…As already de- scribed for non-P. insidiosum isolates, some sterol-targeting antifungal agents, while ineffective on mycelium grown in the absence of sterol, demonstrated antimicrobial activity in culture media containing cholesterol (31,32). Conversely, the presence of cholesterol decreased the growth-inhibitory action of the antibacterial drugs that act by inhibiting the protein synthesis of Pythium isolates (33,34). In this context, the possible changes in the permeability of the plasma membrane of P. insidiosum caused by antifungal drugs may facilitate the entry of antibacterial drugs in the cell, resulting in the synergistic interaction of these drugs.…”

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confidence: 97%

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

Jesus

Ferreiro

Loreto

et al. 2014

Antimicrob Agents Chemother

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We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLSI M38-A2 technique and the checkerboard microdilution method. The main synergisms observed were through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%), and micafungin (70%) and of clarithromycin with micafungin (73.33%). Pythiosis is a life-threatening disease caused by the oomycete Pythium insidiosum, which can cause infections in humans and in animals, such as horses, bovines, cats, dogs, and sheep. Clinically, the disease may manifest in cutaneous, gastrointestinal, vascular, and systemic forms and has been described in tropical and subtropical areas (1). The hyphae of P. insidiosum are morphologically similar to those of certain mucoraceous molds, but P. insidiosum is not a true fungus because it does not synthesize ergosterol, which is the target of most antifungal drugs. Despite this challenge, two cases of pythiosis in humans, one case of ocular pythiosis and one case of pleuropericarditis (2, 3), have been successfully treated using combination antifungal therapy. However, combination antifungal therapy has been ineffective in cases of vascular and disseminated human pythiosis (4).Previous studies have shown that the growth of P. insidiosum is inhibited in vitro by the glycylcycline, macrolide, and tetracycline classes of antibacterial drugs (5, 6). However, studies evaluating the antimicrobial combination of antibacterial and antifungal agents against P. insidiosum have not been performed. In this context, this study evaluated the in vitro combination of the antibacterial drugs azithromycin, clarithromycin, minocycline, or tigecycline with the antifungal drugs amphotericin B, itraconazole, voriconazole, terbinafine, anidulafungin, caspofungin, or micafungin against P. insidiosum.Twenty-eight P. insidiosum isolates obtained from Brazilian cases of equine pythiosis and the reference strains ATCC 58.637 and CBS 101555 were evaluated in this study. The identities of the clinical isolates were confirmed using PCR-based assays (7). The antibacterial drugs azithromycin (Pharma Nostra, Rio de Janeiro, Brazil), clarithromycin (Genix, Anápolis, Brazil), minocycline (Pharma Nostra), and tigecycline (Pfizer, New York, NY) and the antifungal drugs amphotericin B (Sigma-Aldrich, St. Louis, MO), itraconazole (Frangon do Brasil Farmacêutica Ltda., São Paulo, Brazil), voriconazole (Pfizer), terbinafine (Pharma Nostra), anidulafungin (Pfizer), caspofungin (Merck, Darmstadt, Germany), and micafungin (Astellas, Chuo, Japan) were obtained commercially and diluted in dimethyl sulfoxide or distilled water, as recommended, to generate stock solutions. The concentrations of the antimicrobial agents tested were 0.03 to 16 g/ml and 1 to 512 g/ml for the antibacterial and antifungal dr...

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confidence: 97%

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

Jesus

Ferreiro

Loreto

et al. 2014

Antimicrob Agents Chemother

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“…The inability of the genus Pythium to synthesize ergosterol explains the difficulties of antifungal therapy because ergosterol is the target of action for the majority of antifungal agents (19). Interestingly, previous studies have shown that Pythium ultimum and Pythium debaryanum are quite sensitive to the 70S ribosome-active antibiotics, such as tetracyclines and erythromycin (16,17).…”

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confidence: 99%

In Vitro Susceptibility of Pythium insidiosum to Macrolides and Tetracycline Antibiotics

Loreto

Mario

Denardi

et al. 2011

Antimicrob Agents Chemother

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We describe the in vitro activity of macrolides and tetracycline antibiotics against Pythium insidiosum. The MICs were determined according to CLSI procedures (visual MIC) and by a colorimetric method [3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)]. The lowest geometric mean (GM) MIC (MICs in g/ml) (0.39 and 0.7 by visual reading and colorimetric method, respectively) and MIC ranges (0.125 to 2.0) were obtained for minocycline, while the highest MICs were shown for erythromycin (GM of 7.58 and 12.25 by visual reading and colorimetric method, respectively, and MIC ranged from 2 to 32). This significant in vitro activity makes these classes of antibiotics good candidates for experimental treatment of pythiosis.

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“…This study has taken forward our earlier in vitro and in vivo results wherein we have demonstrated the inhibition of P. insidiosum by antibacterial agents while being used as monotherapy. 16–19 This has been observed by us in rabbit Pythium model that linezolid performed significantly better than tigecycline and azithromycin in reducing the infection load. Reduction in the clinical score was highest in rabbits treated with linezolid.…”

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confidence: 80%

Randomized Double-Masked Placebo-Controlled Trial for the Management of Pythium Keratitis: Combination of Antibiotics Versus Monotherapy

Tanna

Bagga

Sharma

et al. 2023

Cornea

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Purpose:The aim of this study was to compare the efficacy of monotherapy (topical linezolid 0.2%) versus a combination of antibiotics (topical linezolid 0.2% and topical azithromycin 1%) for the treatment of Pythium insidiosum keratitis.Methods:Cases of P. insidiosum keratitis were prospectively randomized into group A on topical 0.2% linezolid along with topical placebo (sodium carboxymethyl cellulose [CMC] 0.5%) and group B on a combination of topical 0.2% linezolid and topical 1% azithromycin. Both groups were compared by proportion of both clinical resolution and worsening of keratitis along with the number of therapeutic penetrating keratoplasty (TPK) performed at 3 months.Results:We initially planned N = 66 patients but later limited to 20 (N = 10 in each group) patients owing to one interim analysis. The average size of the infiltrate in group A and B was 5.6 ± 1.5 mm and 4.8 ± 2.0 mm, respectively, with a mean Logarithm of the Minimum Angle of Resolution (logMAR) visual acuity of 2.74 ± 0.55 and 1.79 ± 1.19. At 3 months, from group A, 7 (70%) patients needed TPK and 2 patients had signs of resolution, whereas from group B, 6 (60%) patients achieved complete resolution (P = 0.0003) and 2 were improving while only 1 needed TPK (P = 0.02). The median duration of treatment in group A and B, with the study drugs, was 31 days (17.8–47.8) and 101.5 days (80–123.3), P value = 0.003, respectively. Final visual acuity at 3 months was 2.50 ± 0.81 and 0.75 ± 0.87, P = 0.02, respectively.Conclusions:A combination of topical linezolid and topical azithromycin was found to have superior efficacy than the monotherapy with topical linezolid for the management of Pythium keratitis.

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Protection ofPythiumSpecies Against Antibacterial Antibiotics by Cholesterol

Cited by 8 publications

References 0 publications

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

In Vitro Susceptibility of Pythium insidiosum to Macrolides and Tetracycline Antibiotics

Randomized Double-Masked Placebo-Controlled Trial for the Management of Pythium Keratitis: Combination of Antibiotics Versus Monotherapy

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