scholarly journals Amphotericin B Colloidal Dispersion Combined with Flucytosine with or without Fluconazole for Treatment of Murine Cryptococcal Meningitis

1998 ◽  
Vol 42 (3) ◽  
pp. 528-533 ◽  
Author(s):  
DeAnn M. Diamond ◽  
Madeline Bauer ◽  
Barbra E. Daniel ◽  
Mary Ann E. Leal ◽  
Debra Johnson ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Sole Source ◽  
Colloidal Dispersion ◽  
Intracerebral Injection ◽  
Triple Combination ◽  
Antifungal Effect ◽  
The Brain ◽  
Antifungal Efficacy

ABSTRACT Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused byCryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral injection of C. neoformans. Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity.

scholarly journals Amphotericin B and Fluconazole, a Potent Combination Therapy for Cryptococcal Meningitis

2004 ◽  
Vol 48 (3) ◽  
pp. 985-991 ◽  
Author(s):  
Robert A. Larsen ◽  
Madeline Bauer ◽  
Ann M. Thomas ◽  
J. Richard Graybill
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Sole Source ◽  
Intracerebral Injection ◽  
Full Potential ◽  
Relative Safety ◽  
Antifungal Effects ◽  
Dose Combination ◽  
Widespread Availability ◽  
The Brain

ABSTRACT We evaluated the antifungal activities of amphotericin B, fluconazole, and flucytosine, alone and in combination, in a murine model of cryptococcal meningitis. The objectives were to determine the greatest antifungal effects achievable with these drugs alone or in combination. Meningitis was established in male BALB/c mice weighing 23 to 25 g by intracerebral injection of Cryptococcus neoformans. Treatment was started on day 2. Amphotericin B was tested at 0.3 to 1.3 mg/kg of body weight/day by slow intravenous injection. Fluconazole at 10 to 40 mg/kg/day and flucytosine at 20 to 105 mg/kg/day were administered in the sole source of drinking water. The mice were killed at 16 days, and the numbers of fungal colonies in the brain were quantified. The association between the response and the dose combination was evaluated by local nonparametric response surface methods; 99% confidence intervals were used to evaluate the antifungal effects. Ninety-five percent of the mice treated with amphotericin B at 0.5 mg/kg survived to the end of the experiment, regardless of the fluconazole or flucytosine dose used. The greatest activity was seen with amphotericin B plus fluconazole with or without flucytosine. However, the addition of flucytosine did not increase the antifungal activity. Given the widespread availability of amphotericin B and fluconazole and the relative safety profile of fluconazole compared to that of flucytosine, the full potential of this two-drug combination deserves further evaluation.

scholarly journals Antibacterial and Antifungal Capacity of Three Commercially Available Mouthwashes with Different Concentrations of Chlorhexidine

2021 ◽  
pp. 380-391
Author(s):  
Daniel Chavarría-Bolaños ◽  
Vicente Esparza-Villalpando ◽  
Karol Ramírez
Keyword(s):  
Escherichia Coli ◽  
Dental Plaque ◽  
Inhibitory Effect ◽  
Low Doses ◽  
Antifungal Effect ◽  
Antibacterial And Antifungal ◽  
Antiseptic Solutions ◽  
Antifungal Efficacy ◽  
Support Evidence

Chlorhexidine was introduced almost seven decades ago and has a myriad of applications in dentistry. Few studies have evaluated the antimicrobial and antifungal capacity of different concentrations of chlorhexidine mouthwashes. Therefore, the aim of this study, was to evaluate in vitro, the antibacterial and antifungal capacity of three commercially available mouthwashes in Costa Rica, with different concentrations of chlorhexidine, 0.12%, 0.06%, and 0.03%. The experimental method selected was the Kirby-Bauer method to evaluate the antibacterial and antifungal effect of each compound by measuring the inhibitory effect on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Candida albicans strains, exposed to the antiseptic solutions. All samples showed some degree of antibacterial and antifungal effect. Even though we provide in vitro results, our findings are of relevance since all the species used in our experiment are microorganisms that may be present in dental plaque. Our results further support evidence that oral hygiene regimens may include mouthwashes with low doses of chlorhexidine and maintain reasonable antibacterial and antifungal efficacy.

scholarly journals A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.

2019 ◽  
Vol 4 ◽  
pp. 8 ◽  
Author(s):  
Nguyen Thi Thuy Ngan ◽  
Nguyen Thi Hoang Mai ◽  
Nguyen Le Nhu Tung ◽  
Nguyen Phu Huong Lan ◽  
Luong Thi Hue Tai ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Treatment Guidelines ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Receptor Modulator ◽  
Open Label Trial ◽  
Early Fungicidal Activity

Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole. Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively. Discussion: The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation. Trial registration: Clinicaltrials.gov NCT03112031 (11/04/2017)

scholarly journals Comparison of In Vitro Activity of Liposomal Nystatin againstAspergillus Species with Those of Nystatin, Amphotericin B (AB) Deoxycholate, AB Colloidal Dispersion, Liposomal AB, AB Lipid Complex, and Itraconazole

1999 ◽  
Vol 43 (5) ◽  
pp. 1264-1266 ◽  
Author(s):  
Karen L. Oakley ◽  
Caroline B. Moore ◽  
David W. Denning
Keyword(s):  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Antifungal Agents ◽  
Geometric Mean ◽  
Colloidal Dispersion ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Lipid Complex

ABSTRACT We compared the in vitro activity of liposomal nystatin (Nyotran) with those of other antifungal agents against 60Aspergillus isolates. Twelve isolates were itraconazole resistant. For all isolates, geometric mean (GM) MICs (micrograms per milliliter) were 2.30 for liposomal nystatin, 0.58 for itraconazole, 0.86 for amphotericin B (AB) deoxycholate, 9.51 for nystatin, 2.07 for liposomal AB, 2.57 for AB lipid complex, and 0.86 for AB colloidal dispersion. Aspergillus terreus (GM, 8.72 μg/ml; range, 8 to 16 μg/ml) was significantly less susceptible to all of the polyene drugs than all other species (P = 0.0001).

scholarly journals In VitroActivities of a Wide Panel of Antifungal Drugs against Various Scopulariopsis and Microascus Species

2015 ◽  
Vol 59 (9) ◽  
pp. 5827-5829 ◽  
Author(s):  
Magdalena Skóra ◽  
Małgorzata Bulanda ◽  
Tomasz Jagielski
Keyword(s):  
Amphotericin B ◽  
Effective Concentration ◽  
Antifungal Drugs ◽  
Antifungal Effect ◽  
Content Type ◽  
Minimal Effective Concentration

ABSTRACTThein vitroactivities of 11 antifungal drugs against 68ScopulariopsisandMicroascusstrains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50and MEC50were 1 µg/ml for both drugs, whereas the MIC90and MEC90were 4 µg/ml and 16 µg/ml, respectively.

Fluconazole and Amphotericin B for Cryptococcal Meningitis

1996 ◽  
Vol 30 (12) ◽  
pp. 1408-1410 ◽  
Author(s):  
Amy B Clark ◽  
Bob L Lobo ◽  
Michael S Gelfand
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Patient Population ◽  
Standard Therapy ◽  
Alternative Therapy ◽  
Poor Response ◽  
Case Summary

OBJECTIVE: To describe a patient with cryptococcal meningitis treated with the combination of amphotericin B and fluconazole. CASE SUMMARY: A 41-year-old woman with cryptococcal meningitis who was not infected with HIV was treated with a combination of amphotericin B and fluconazole because she did not respond to amphotericin B alone and could not tolerate amphotericin B with flucytosine. She improved clinically, but it is unclear whether the combination was beneficial. DISCUSSION: Standard therapy for cryptococcal meningitis is amphotericin B with or without flucytosine. Fluconazole is an alternative therapy, but its efficacy has not been documented in the patient population not infected with HIV. Theoretically, the combination of amphotericin B and fluconazole is antagonistic, but in vitro and in vivo data suggest that antagonism may not occur. The combination of amphotericin B and fluconazole in cryptococcal meningitis has not been evaluated in clinical trials, and its use is not recommended. CONCLUSIONS: A patient with cryptococcal meningitis was treated with the combination of amphotericin B and fluconazole because of a poor response to amphotericin B monotherapy and intolerance to flucytosine. It is unclear whether her clinical response was a result of the combination.

scholarly journals Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

2007 ◽  
Vol 44 (2) ◽  
pp. 47-56 ◽  
Author(s):  
J. Porubcová ◽  
E. Dvorožňáková ◽  
Z. Ševčíková
Keyword(s):  
Immune Response ◽  
Amphotericin B ◽  
Echinococcus Multilocularis ◽  
Proliferative Response ◽  
Larval Growth ◽  
Colloidal Dispersion ◽  
Cell Subpopulation ◽  
Th2 Immune Response ◽  
Ifn Γ

AbstractThe effect of amphotericin B colloidal dispersion (ABCD) on selected immunological parameters and growth of the larval cysts in mice infected intraperitoneally with Echinococcus multilocularis protoscoleces was observed. ABCD was administered at a dose 10 mg/kg body weight twice a week from week 5 to 10 post infection (p.i.). The Echinococcus infection suppressed the proliferative response of splenic T lymphocytes to nonspecific mitogen concanavalin A throughout almost the whole course of the experiment and ABCD administration did not affect this inhibittion. The increase in the proliferative response of B lymphocytes to lipopolysaccharide was found in infected mice with ABCD treatment from week 6 to 10 p.i. ABCD induced a significant rise of the splenic CD4 T cell subpopulation in infected mice only on week 6 p.i. The CD8 T subpopulation was not influenced by the therapy. The level of serum Th1 cytokine IFN-γ in infected and ABCD treated mice was elevated only at week 8 p.i., while the level of serum Th2 cytokine IL-5 was not influenced by the therapy. The ABCD treatment inhibited the IFN-γ production by splenocytes in vitro from week 6 to 10 p.i. On the contrary, the IL-5 production in vitro was stimulated at weeks 8 and 12 p.i. None antiparasitic effect of ABCD on larval growth was determined.Results suggest that amphotericin B colloidal dispersion did not affect the inhibited Th1 immune response after parasite infection. On the contrary, ABCD advanced the Th2 immune response development, which allows the progressive growth of the parasite.

scholarly journals Dosage-Dependent Antifungal Efficacy of V-Echinocandin (LY303366) against Experimental Fluconazole-Resistant Oropharyngeal and Esophageal Candidiasis

2001 ◽  
Vol 45 (2) ◽  
pp. 471-479 ◽  
Author(s):  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Andreas H. Groll ◽  
Tin Sein ◽  
Robert L. Schaufele ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Study Groups ◽  
Esophageal Candidiasis ◽  
Echinocandin B ◽  
Hepatic Transaminase ◽  
Fluconazole Resistant ◽  
Semisynthetic Derivative ◽  
Antifungal Efficacy

ABSTRACT V-echinocandin (VER-002; LY303366) is a semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1, 3)-β-d-glucan synthase. We studied the antifungal efficacy, the concentrations in saliva and tissue, and the safety of VER-002 at escalating dosages against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant Candida albicans in immunocompromised rabbits. Study groups consisted of untreated controls, animals treated with VER-002 at 1, 2.5, and 5 mg/kg of body weight/day intravenously (i.v.), animals treated with fluconazole at 2 mg/kg/day i.v., or animals treated with amphotericin B at 0.3 mg/kg/day. VER-002-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, esophagus, stomach, and duodenum in comparison to that for untreated controls. VER-002 also was superior to amphotericin B and fluconazole in clearing the organism from all sites studied. These in vivo findings are consistent with the results of in vitro time-kill assays, which demonstrated that VER-002 has concentration-dependent fungicidal activity. Esophageal tissue VER-002 concentrations were dosage proportional and exceeded the MIC at all dosages. Echinocandin concentrations in saliva were greater than or equal to the MICs at all dosages. There was no elevation of serum hepatic transaminase, alkaline phosphatase, bilirubin, potassium, or creatinine levels in VER-002-treated rabbits. In summary, the echinocandin VER-002 was well tolerated, penetrated the esophagus and salivary glands, and demonstrated dosage-dependent antifungal activity against fluconazole-resistant esophageal candidiasis in immunocompromised rabbits.

In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

2007 ◽  
Vol 293 (5) ◽  
pp. C1698-C1708 ◽  
Author(s):  
Y. Jeffrey Wu ◽  
Leslie L. Muldoon ◽  
Csanad Varallyay ◽  
Sheila Markwardt ◽  
Richard E. Jones ◽  
...  
Keyword(s):  
Cell Sorting ◽  
B Lymphocyte ◽  
Protamine Sulfate ◽  
Mononuclear Leukocytes ◽  
Intracerebral Injection ◽  
Sulfate Complex ◽  
Human Dose ◽  
The Brain

Cellular labeling with ferumoxides (Feridex IV) superparamagnetic iron oxide nanoparticles can be used to monitor cells in vivo by MRI. The objective of this study was to use histology and MRI to evaluate an in vivo, as opposed to in vitro, technique for labeling of mononuclear leukocytes as a means of tracking inflammatory processes in the brain. Long-Evans rats were intravenously injected with 20 mg/kg ferumoxides, ferumoxtran-10, or ferumoxytol with or without protamine sulfate. Leukocytes and splenocytes were evaluated by cell sorting and iron histochemistry or were implanted into the brain for MRI. Injection of ferumoxides/protamine sulfate complex IV resulted in iron labeling of leukocytes (ranging from 7.4 ± 0.5% to 12.5 ± 0.9% with average 9.2 ± 0.8%) compared with ferumoxides (ranging from 3.9 ± 0.4% to 6.3 ± 0.5% with average 5.0 ± 0.5%) or protamine sulfate alone (ranging from 0% to 0.9 ± 0.7% with average 0.3 ± 0.3%). Cell sorting analysis indicated that iron-labeled cells were enriched for cell types positive for the myelomonocytic marker (CD11b/c) and the B lymphocyte marker (CD45RA) and depleted in the T cell marker (CD3). Neither ferumoxtran-10 nor ferumoxytol with protamine sulfate labeled leukocytes. In vivo ferumoxides/protamine sulfate-loaded leukocytes and splenocytes were detected by MRI after intracerebral injection. Ferumoxides/protamine complex labeled CD45RA-positive and CD11b/c-positive leukocytes in vivo without immediate toxicity. The dose of feumoxides in this report is much higher than the approved human dose, so additional animal studies are required before this approach could be translated to the clinic. These results might provide useful information for monitoring leukocyte trafficking into the brain.

scholarly journals Antifungal properties of sodium peroxide and sodium hypochlorite as a denture cleanser for full acrylic denture in vitro

2008 ◽  
Vol 20 (1) ◽  
Author(s):  
Gantini Subrata
Keyword(s):  
Sodium Hypochlorite ◽  
Contact Time ◽  
Optimum Concentration ◽  
Sodium Peroxide ◽  
Antifungal Effect ◽  
Low Concentration ◽  
Base Solution ◽  
Denture Cleansers ◽  
Antifungal Efficacy

Widely used materials are reported as denture cleansers are peroxide and hypochlorite. Many contradictions on the effectiveness of the commercial peroxide base solution against Candida albicans (C. albicans). Low concentration sodium hypochlorite (0.5%) is used as a household sanitizer. But it is still unknown whether it has an antifungal effect, what is the optimum concentration and contact time to destroy the yeast. The purpose of this study is to examine the antifungal efficacy of commercial peroxide-based soaking solution and low concentration sodium hypochlorite against C. albicans, to determine the optimum concentration and contact time, and at the end, to obtain an effective denture soaking solution which is safe to use, easy to get, affordable and could be used to destroy C. albicans on dentures. The research conducted was an in vitro practical test for surface disinfectant. Sixty plates of acrylic which were already incubated with C. albicans are immersed in peroxide and hypochlorite base soaking solution in different concentration and contact time. The result showed that peroxide base was not effective to C. albicans and hypochlorite base solution can destroy C. albicans in 10 minutes at a concentration of 0,125%. Thus, the use of low concentration sodium hypochlorite as a denture soaking solution can be suggested.

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