levoleucovorin and Candidiasis

The increasing number of Candida infections, especially those caused by non-C. albicans species and resistant strains, is a serious medical problem.. In this study, the antifungal activity of base analogues, 5-flucytosine (5-FC) and 5-fluorouracil (5-FU), was tested against planktonic cells as well as against mature biofilm.. Tests were performed according the EUCAST methodology. Antibiofilm effectiveness of tested drugs was determined by the crystal violet staining method. The cytotoxicity assays was performed according to the ISO 10993-5 norm.. 5-FC and 5-FU were effective against fifteen fluconazole resistant Candida glabrata strains with an average minimal inhibitory concentration (MIC) of 0.152mg/L and 0.39mg/L, respectively. Folinic acid (folinate- e.g., leucovorin) is a common drug used in oncology simultaneously with 5-FU. In our tests folinate was able to lower MIC for 5-FC from 0.152 to 0.058mg/L (P<0.05). In the biofilm assay 5-FU and 5-FC alone did not induce any changes in the biomass of mature biofilm. Addition of folinate to each base analogue resulted in up to 90% reduction of biomass. Viability tests show that a concentration of 64mg/L of 5-FC and 5-FU supplemented with folinate can be fungicidal against mature biofilms of some Candida isolates. No cytotoxic effect was found for combination of FOL and 5-FC.. Therapy of 5-FU+folinate is well known in cancer treatment, in this study we reveal the beneficial effect of folinate on antifungal activity of 5-FC as well as the antifungal potential of 5-FU+folinate.

Topics: Antifungal Agents; Biofilms; Candida albicans; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Flucytosine; Fluorouracil; Gentian Violet; Leucovorin; Microbial Sensitivity Tests; Microbial Viability

Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis.. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation.. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases.. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Candidiasis; Endoscopy; Esophageal Neoplasms; Fluorouracil; Hematoporphyrins; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Photochemotherapy; Photosensitizing Agents; Treatment Outcome

Elucidation of the mechanism of action of epigallocatechin-3-gallate (EGCG) against Candida albicans and demonstration of the connection between its antifolate activity and other metabolic pathways involved in C. albicans survival are the major objectives of this study.. C. albicans ATCC 10231 and 12 clinical isolates were used. MICs of EGCG against C. albicans were determined according to NCCLS. C. albicans dihydrofolate reductase (DHFR) was purified using methotrexate-affinity chromatography and its inhibition by EGCG studied by spectroscopic techniques. Synergy experiments were performed by chequerboard tests by combining eight doubling concentrations of EGCG with another eight dilutions of azole compounds or terbinafine. Reversion experiments with leucovorin or S-adenosylmethionine were carried out, and the content of ergosterol was determined by a spectrophotometric method.. EGCG is an efficient inhibitor of C. albicans DHFR (K(i) = 0.7 microM). As with other antifolates, the effects of EGCG on C. albicans can be highly attenuated by growing the cells in the presence of leucovorin. EGCG showed synergy with inhibitors of the ergosterol biosynthesis pathway in C. albicans such as azole antifungals and terbinafine. We demonstrate that by disturbing the folate metabolism, EGCG can inhibit ergosterol production. The molecular connection between the pathways is discussed.. EGCG acts as an antifolate compound on C. albicans, disturbing its folic acid metabolism. This effect could explain the molecular mechanism for the synergy between EGCG and azole antifungals, and could represent a starting point for therapies involving antifolates and azoles used as an alternative for the treatment of C. albicans infections.

Topics: Antifungal Agents; Azoles; Candida albicans; Candidiasis; Catechin; Drug Synergism; Enzyme Inhibitors; Ergosterol; Folic Acid; Folic Acid Antagonists; Fungal Proteins; Leucovorin; Microbial Sensitivity Tests; Models, Biological; Naphthalenes; S-Adenosylmethionine; Spectrum Analysis; Terbinafine; Tetrahydrofolate Dehydrogenase; Vitamin B Complex

Topics: Administration, Oral; Adolescent; Amphotericin B; Anorexia; Blood Platelets; Blood Transfusion; Candidiasis; Drug Eruptions; Humans; Infusions, Parenteral; Injections, Intramuscular; Leucovorin; Methotrexate; Nausea; Osteosarcoma; Pneumothorax; Stomatitis; Vomiting