Cryptococcosis is an invasive mycosis caused mainly by Cryptococcus gattii and C. neoformans and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against Cryptococcus spp. However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against C. neoformans and C. gattii. In this study, DH inhibited the growth of several C. neoformans and C. gattii strains at concentrations ranging from 15.62 to 62.50 μg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 μg/mL. In biofilm, DH treatment reduced Cryptococcus spp. biomass at a level comparable to AMB, with a significant reduction (85%) for C. neoformans biofilms. The metabolic activity of C. neoformans and C. gattii biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of C. neoformans and C. gattii, opening perspectives for further studies with DH in vivo.
- MeSH
- Antifungal Agents * pharmacology MeSH
- Biofilms * drug effects MeSH
- Cryptococcus gattii * drug effects MeSH
- Cryptococcus neoformans * drug effects growth & development MeSH
- Duloxetine Hydrochloride * pharmacology MeSH
- Cryptococcosis drug therapy microbiology MeSH
- Microbial Sensitivity Tests * MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Aspergillus fumigatus pathogenicity MeSH
- Bacterial Infections diagnosis therapy MeSH
- Candida albicans pathogenicity MeSH
- Cryptococcus gattii pathogenicity MeSH
- Cryptococcus neoformans pathogenicity MeSH
- Cytomegalovirus Infections diagnostic imaging diagnosis therapy MeSH
- Herpesviridae Infections diagnosis drug therapy MeSH
- Epstein-Barr Virus Infections diagnosis MeSH
- Infections diagnosis therapy MeSH
- Humans MeSH
- Mucorales pathogenicity MeSH
- Mycoses diagnostic imaging diagnosis therapy MeSH
- Pneumocystis pathogenicity MeSH
- Strongyloides pathogenicity MeSH
- Toxoplasma pathogenicity MeSH
- Lung Transplantation * MeSH
- Check Tag
- Humans MeSH
Kryptokokální meningitida (KM) je potenciálně fatální onemocnění. Popisujeme úspěšnou léčbu pomocí Ommaya rezervoáru a intratekální injekce amfotericinu B ke zvládnutí refrakterní cerebrální kryptokokózy způsobené Cryptococcus gattii AFLP4/VGI. U 63letého pacienta s hypertermií a bolestmi hlavy v trvání 2 týdnů byla diagnostikována KM. Byla zahájena kombinovaná léčba amfotericinem B a 5-flucytosinem a následována léčbou flukonazolem. Po 7 měsících byl refrakterní k tradiční léčbě KM a byla zvolena záchranná léčba pomocí Ommaya rezervoáru a intratékální injekce amfotericinu B. Neurologické příznaky postupně odezněly bez zřejmého relapsu během 12 měsíců sledování. Izolát byl přešetřen kultivací na médiu s kanavaninem, glycinem a bromthymolovou modří a molekulární typizací pomocí URA5 byl identifikován Cryptococcus gattii AFLP4/VGI. Ommaya rezervoár lze doporučit jako alternativní léčbu KM vyvolané Cryptococcus gattii AFLP4/VGI, která špatně odpovídá na standardní léčebné režimy.
Cryptococcal meningitis (CM) is a potentially fatal disease. We report successful treatment with the Ommaya reservoir and intrathecal injection of amphotericin B for the control of refractory cerebral cryptococcosis due to Cryptococcus gattii AFLP4/VGI. A 63-year-old male patient presented with a 2-week history of fever and headache, and was he diagnosed with CM. Combined amphotericin B and 5-flucytosine treatment was initiated and followed by fluconazole therapy. After 7 months, he was refractory to traditional CM treatment and received salvage therapy with an Ommaya reservoir and intrathecal injection of amphotericin B. His neurological symptoms recovered gradually with no evidence of relapse during 12-month follow-up. The isolate was re-identified by culturing in canavanine-glycine-bromothymol Blue media and by molecular typing using URA5 as Cryptococcus gattii AFLP4/VGI. The Ommaya reservoir could serve as an alternative treatment for Cryptococcus gattii AFLP4/VGI-induced CM, which responds poorly to standard regimens.
- Keywords
- Ommaya rezervoár,
- MeSH
- Amphotericin B therapeutic use MeSH
- Antifungal Agents therapeutic use MeSH
- Cryptococcus gattii isolation & purification MeSH
- Flucytosine therapeutic use MeSH
- Fluconazole MeSH
- Hydrocephalus etiology MeSH
- Drug Therapy, Combination MeSH
- Meningitis, Cryptococcal * diagnosis drug therapy physiopathology MeSH
- Drug Resistance MeSH
- Drug Delivery Systems MeSH
- Middle Aged MeSH
- Humans MeSH
- Cerebral Ventricles * drug effects MeSH
- Recurrence MeSH
- Injections, Spinal MeSH
- Catheters, Indwelling * MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
Cryptococcosis is caused by members of the Cryptococcus neoformans/Cryptococcus gattii species complex. Based on molecular identification, these two species have been further differentiated into molecular types. The aim of this work was to characterize clinical cryptococcal isolates recovered from six hospitals in Northeast Mexico from 1995 to 2011. One hundred and sixty-six isolates, which were characterized by biochemical tests and in vitro susceptibility to amphotericin B, fluconazole, and voriconazole, and M13 PCR fingerprinting, were included in this study. Utilizing phenotypic tests, 153 isolates (92.16 %) were identified as C. neoformans and 13 (7.83 %) as C. gattii. All isolates were susceptible to all antifungals tested. Employing M13 PCR fingerprinting, eight molecular types were detected. VNI was the most common genotype (124 cases; 74.6 %), followed by VNII (15 cases; 9 %), VNIII (8 cases; 4.8 %), VNIV (6 cases; 3.6 %), VGI (6 cases; 3.6 %), VGII (3 cases; 1.8 %), and VGIII and VGIV (2 cases, 1.2 % each). We confirm the presence of C. gattii in clinical isolates in Northeast Mexico, and a high clonal diversity in the studied strains of C. neoformans/C. gattii species complex.
- MeSH
- Antifungal Agents pharmacology MeSH
- Cryptococcus gattii classification genetics isolation & purification MeSH
- Cryptococcus neoformans classification genetics isolation & purification MeSH
- DNA Fingerprinting MeSH
- Adult MeSH
- Cryptococcosis epidemiology microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Adolescent MeSH
- Young Adult MeSH
- Molecular Epidemiology MeSH
- Molecular Typing * MeSH
- Mycological Typing Techniques * MeSH
- Hospitals MeSH
- Polymerase Chain Reaction MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Mexico epidemiology MeSH
- MeSH
- Cryptococcus gattii * genetics isolation & purification classification pathogenicity growth & development MeSH
- Epidemics MeSH
- Climate Change MeSH
- Cryptococcosis etiology microbiology veterinary MeSH
- Yeasts genetics classification pathogenicity growth & development MeSH
- Humans MeSH
- Disease Transmission, Infectious MeSH
- Temperature MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
