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1.
EBioMedicine ; 102: 105042, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38471990

RESUMEN

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).


Asunto(s)
COVID-19 , Compuestos Organofosforados , Ubiquinona , Animales , Femenino , Humanos , Ratones , Antivirales , COVID-19/prevención & control , Profilaxis Posexposición , SARS-CoV-2 , Resultado del Tratamiento , Ubiquinona/análogos & derivados
2.
Am J Trop Med Hyg ; 86(2): 261-3, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22302860

RESUMEN

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.


Asunto(s)
Histoplasmosis/diagnóstico , Histoplasmosis/epidemiología , Neoplasias Cutáneas/tratamiento farmacológico , África/epidemiología , Anciano , Antifúngicos/uso terapéutico , Histoplasmosis/patología , Humanos , Itraconazol/uso terapéutico , Masculino , Peloterapia , Resultado del Tratamiento
3.
Diagn Microbiol Infect Dis ; 71(3): 286-90, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21855248

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is associated with a high mortality rate. Treatment is challenging in patients with allergy to vancomycin. Herein, we describe a case of MRSA bacteremia secondary to medical device infection with MRSA that was complicated by MRSA meningitis. This case provides evidence for a possible role of combination therapy of daptomycin, linezolid, and rifampin in cases of MRSA meningitis and bacteremia.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Meningitis Bacterianas/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Acetamidas/farmacología , Acetamidas/uso terapéutico , Antibacterianos/farmacología , Daptomicina/farmacología , Daptomicina/uso terapéutico , Quimioterapia Combinada , Humanos , Linezolid , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Oxazolidinonas/farmacología , Oxazolidinonas/uso terapéutico , Rifampin/farmacología , Rifampin/uso terapéutico , Resultado del Tratamiento
4.
J Med Microbiol ; 59(Pt 11): 1383-1386, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20688947
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