RESUMEN
IMPORTANCE: Skin cancer is the most common cancer in the United States, and men experience higher rates of skin cancer than women. Despite publicized preventative measures, men are less likely than women to use sunscreen. OBJECTIVE: To assess men's motivations, behaviors, and preferred product characteristics towards daily sunscreen use. DESIGN AND SETTING: Cross-sectional online survey of 705 men, administered July– August 2019, using Survey Monkey and distributed through Amazon Mechanical Turk. PARTICIPANTS: Men ages 20–70, having completed at least High School/GED, and living in the United States were eligible. Sampling strategy ensured diversity in terms of race, ethnicity, and sexual orientation. Main Outcome(s) and Measures: Men’s sunscreen use, behaviors, and preferred skincare product characteristics. RESULTS: Final participants included 705 men. The most frequent skincare products used regularly were liquid soap/body wash (65%), bar soap (47%), and moisturizers (32%). Most men (n=612; 83%) reported not using sunscreen daily, and 38% reported using sunscreen weekly. Income was related to daily and weekly sunscreen use, as males who earned between $40-$50,000 annually used sunscreen less often compared to people who earned $100,000 annually (OR 0.54%, 95% CI −0.34% to .88%; P = .01). Age, sexual orientation, race, ethnicity, and region were not related to daily or weekly sunscreen use. Main motivators for daily sunscreen use included reducing skin cancer risk (n=575; 82%) and looking younger (n=299; 42%). CONCLUSIONS AND RELEVANCE: This survey shows lapses in evidenced-based sunscreen behaviors to reduce skin cancer among men. Campaigns to reduce skin cancer should focus on increasing men's interest in daily sunscreen use and adherence to wearing sun-protective products. J Drugs Dermatol. 2021;20(1):88-93. doi:10.36849/JDD.5470.
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Hombres/psicología , Cuidados de la Piel/psicología , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control , Protectores Solares/administración & dosificación , Adulto , Anciano , Comportamiento del Consumidor/estadística & datos numéricos , Estudios Transversales , Femenino , Educación en Salud , Humanos , Masculino , Persona de Mediana Edad , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Cuidados de la Piel/estadística & datos numéricos , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Quemadura Solar/complicaciones , Quemadura Solar/patología , Encuestas y Cuestionarios/estadística & datos numéricos , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: This clinical study assessed the safety and efficacy of an investigational topical product for the treatment of onychomycosis (nail fungus). METHOD: A prospective, multi-center, single-arm, self-controlled clinical investigation was done with adult subjects that met the inclusion criteria, primarily culture-confirmed dermatophyte infection of at least one great toe. Subjects self-treated in a weekly regimen of topical application for six months, with clinical assessment at one, three, and six months. Primary efficacy endpoint was clearance of fungal nail infection after six months of weekly treatment. Primary safety endpoint was freedom from product-related adverse events for the duration of the treatment term. RESULTS: Fifty males and 13 females, ages 24 to 65, infected with Trichophyton (n=62) or Epidermophyton (n=1) were enrolled; 53 completed six months of assessment. Sixty percent showed improvement in clinical parameters (nail color, nail plate involvement, onycholysis, thickness, and hyperkeratosis) at six months. Cumulative rates of dermatophyte-negative culture results (test of cure) were 28, 36, and 62 percent of subjects after one, three, and six months of treatment, respectively. Three minor adverse events were device-related, with no unanticipated or serious adverse events. LIMITATIONS: This study was single-arm and self-controlled; 53 of 63 enrolled subjects completed the study. CONCLUSION: This study describes a new topical medical device with safety and efficacy profiles that compare favorably to results reported for topically applied onychomycosis drug treatments.
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Materiales Biocompatibles/uso terapéutico , Onicomicosis/tratamiento farmacológico , Polímeros/uso terapéutico , Administración Tópica , Adulto , Anciano , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/efectos adversos , Epidermophyton/aislamiento & purificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Onicomicosis/microbiología , Polímeros/administración & dosificación , Polímeros/efectos adversos , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Trichophyton/aislamiento & purificación , Adulto JovenRESUMEN
Despite substantially higher skin cancer risks, little research has investigated men's attitudes about skin cancer and how those attitudes relate to their risks of developing skin cancer. This study aims to close the gap in research, regarding men's perceptions and behaviors about skin cancer, sun exposure, and tanning. This study utilized a cross-sectional survey of 705 men recruited from Amazon Mechanical Turk (MTurk), reporting attitudes and behaviors towards sun exposure, tanning, and sun protection. While the majority of men reported large daily outdoor activities, that their skin frequently burns with sun exposure, and riskier perceptions of tanning, only a minority reported daily use of sunscreen or most other sun protective behaviors. More sun protection methods were associated with more frequent use of sunscreen and less positive tanning perceptions. Men consistently engaged in high-risk behaviors for developing skin cancer, but they did not engage highly in protective behaviors to mitigate their risk. The findings can help improve clinical and public health interventions to lower men's risk of skin cancer with strong messages about sunscreen use and sun protective methods.
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Neoplasias Cutáneas , Quemadura Solar , Estudios Transversales , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Hombres , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/prevención & control , Quemadura Solar/tratamiento farmacológico , Protectores Solares/uso terapéuticoRESUMEN
Bacillus anthracis, the causative agent of anthrax, can produce fatal disease when it is inhaled or ingested by humans. Dalbavancin, a novel, semisynthetic lipoglycopeptide, has potent activity, greater than that of vancomycin, against Gram-positive bacteria and a half-life in humans that supports once-weekly dosing. Dalbavancin demonstrated potent in vitro activity against B. anthracis (MIC range, < or =0.03 to 0.5 mg/liter; MIC(50) and MIC(90), 0.06 and 0.25 mg/liter, respectively), which led us to test its efficacy in a murine inhalation anthrax model. The peak concentrations of dalbavancin in mouse plasma after the administration of single intraperitoneal doses of 5 and 20 mg/kg of body weight were 15 and 71 mg/kg, respectively. At 20 mg/kg, the dalbavancin activity was detectable for 6 days after administration (terminal half-life, 53 h), indicating that long intervals between doses were feasible. The mice were challenged with 50 to 100 times the median lethal dose of the Ames strain of B. anthracis, an inoculum that kills untreated animals within 4 days. The efficacy of dalbavancin was 80 to 100%, as determined by the rate of survival at 42 days, when treatment was initiated 24 h postchallenge with regimens of 15 to 120 mg/kg every 36 h (q36h) or 30 to 240 mg/kg every 72 h (q72h). A regimen of ciprofloxacin known to protect 100% of animals was tested in parallel. Delayed dalbavancin treatment (beginning 36 or 48 h postchallenge) with 60 mg/kg q36h or 120 mg/kg q72h still provided 70 to 100% survival. The low MICs and long duration of efficacy in vivo suggest that dalbavancin may have potential as an alternative treatment or for the prophylaxis of B. anthracis infections.
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Carbunco/tratamiento farmacológico , Antibacterianos , Bacillus anthracis/efectos de los fármacos , Teicoplanina/análogos & derivados , Administración por Inhalación , Animales , Carbunco/microbiología , Carbunco/mortalidad , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Bacillus anthracis/patogenicidad , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Teicoplanina/administración & dosificación , Teicoplanina/farmacocinética , Teicoplanina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis. METHODS: Adults with invasive candidiasis were randomly assigned to receive either intravenous anidulafungin or intravenous fluconazole. All patients could receive oral fluconazole after 10 days of intravenous therapy. The primary efficacy analysis assessed the global response (clinical and microbiologic) at the end of intravenous therapy in patients who had a positive baseline culture. Efficacy was also assessed at other time points. RESULTS: Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a "center effect"; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, -1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P=0.13). CONCLUSIONS: Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. (ClinicalTrials.gov number, NCT00056368 [ClinicalTrials.gov]).
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Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Fluconazol/uso terapéutico , Fungemia/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anidulafungina , Antifúngicos/efectos adversos , Candida/aislamiento & purificación , Candidiasis/mortalidad , Método Doble Ciego , Equinocandinas , Femenino , Fluconazol/efectos adversos , Fungemia/mortalidad , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/efectos adversos , Resultado del TratamientoRESUMEN
The hierarchical structure of bone, involving micro-scale organization and interaction of material components, is a critical determinant of macro-scale mechanics. Changes in whole-bone morphology in response to the actions of individual genes, physiological loading during life, or evolutionary processes, may be accompanied by alterations in underlying mineralization or architecture. Here, we used nanoindentation to precisely measure compressive stiffness in the femoral mid-diaphysis of mice that had experienced 37 generations of selective breeding for high levels of voluntary wheel running (HR). Mice (n = 48 total), half from HR lines and half from non-selected control (C) lines, were divided into two experimental groups, one with 13-14 weeks of access to a running wheel and one housed without wheels (n = 12 in each group). At the end of the experiment, gross and micro-computed tomography (microCT)-based morphometric traits were measured, and reduced elastic modulus (E(r)) was estimated separately for four anatomical quadrants of the femoral cortex: anterior, posterior, lateral, and medial. Two-way, mixed-model analysis of covariance (ancova) showed that body mass was a highly significant predictor of all morphometric traits and that structural change is more apparent at the microCT level than in conventional morphometrics of whole bones. Both line type (HR vs. C) and presence of the mini-muscle phenotype (caused by a Mendelian recessive allele and characterized by a approximately 50% reduction in mass of the gastrocnemius muscle complex) were significant predictors of femoral cortical cross-sectional anatomy. Measurement of reduced modulus obtained by nanoindentation was repeatable within a single quadrant and sensitive enough to detect inter-individual differences. Although we found no significant effects of line type (HR vs. C) or physical activity (wheel vs. no wheel) on mean stiffness, anterior and posterior quadrants were significantly stiffer (P < 0.0001) than medial and lateral quadrants (32.67 and 33.09 GPa vs. 29.78 and 30.46 GPa, respectively). Our findings of no significant difference in compressive stiffness in the anterior and posterior quadrants agree with previous results for mice, but differ from those for large mammals. Integrating these results with others from ongoing research on these mice, we hypothesize that the skeletons of female HR mice may be less sensitive to the effects of chronic exercise, due to decreased circulating leptin levels and potentially altered endocannabinoid signaling.
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Huesos/fisiología , Actividad Motora/fisiología , Selección Genética , Adaptación Fisiológica/fisiología , Animales , Evolución Biológica , Índice de Masa Corporal , Cruzamiento , Fuerza Compresiva , Femenino , Ratones , Ratones Endogámicos ICR , Modelos Animales , Reproducibilidad de los Resultados , Microtomografía por Rayos X/métodosRESUMEN
The glycine receptor (GlyR) is a ligand-gated ion channel and member of the nicotinic acetylcholine receptor superfamily. Acting as allosteric modulators of receptor function, drugs such as alcohol and volatile anesthetics enhance the function of GlyRs. The actions of these drugs at inhibitory receptors in the brain and spinal cord are thought to produce many of the physiological effects associated with their use. The actions of ethanol on the GlyR have been well studied on the macroscopic, whole cell level. We examined the effects of 3 microM glycine +/- 50 or 200 mM ethanol on outside-out patches pulled from Xenopus laevis oocytes expressing wild-type alpha1 GlyR, to determine the effects of alcohol at the single-channel level. Alcohol enhanced GlyR function in a very specific manner. It had minimal effects on open and closed dwell times and likelihood. Instead, ethanol potentiated GlyR function almost exclusively by increasing burst durations and increasing the number of channel openings per burst, without affecting the percentage of open time within bursts. Kinetic modeling suggests that ethanol increases burst durations by decreasing the rate of glycine unbinding.
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Etanol/farmacología , Receptores de Glicina/antagonistas & inhibidores , Receptores de Glicina/fisiología , Animales , Sinergismo Farmacológico , Femenino , Activación del Canal Iónico/efectos de los fármacos , Activación del Canal Iónico/fisiología , Oocitos/metabolismo , Técnicas de Placa-Clamp/métodos , Unión Proteica/efectos de los fármacos , Unión Proteica/fisiología , Receptores de Glicina/metabolismo , Xenopus laevisRESUMEN
Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t>MIC). The concentration-dependent target was an area under the concentration-time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was
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Antibacterianos/farmacocinética , Simulación por Computador , Modelos Biológicos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Teicoplanina/análogos & derivados , Antibacterianos/administración & dosificación , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Esquema de Medicación , Humanos , Pruebas de Sensibilidad Microbiana , Método de Montecarlo , Enfermedades Cutáneas Bacterianas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Streptococcus/efectos de los fármacos , Streptococcus/crecimiento & desarrollo , Teicoplanina/administración & dosificación , Teicoplanina/farmacocinética , Vancomicina/farmacocinéticaRESUMEN
Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin.
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Antibacterianos/farmacología , Bacteriemia/microbiología , Cateterismo , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Teicoplanina/análogos & derivados , Antibacterianos/química , Bacteriemia/etiología , ADN Bacteriano/análisis , Electroforesis en Gel de Campo Pulsado , Bacterias Grampositivas/genética , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/etiología , Humanos , Pruebas de Sensibilidad Microbiana , Ensayos Clínicos Controlados Aleatorios como Asunto , Teicoplanina/química , Teicoplanina/farmacología , Vancomicina/farmacologíaRESUMEN
Dalbavancin is an injectable, next generation lipoglycopeptide with an extended serum elimination half-life. Once-weekly dosing has been successful for treatment of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR-BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was initiated in 2003, and results are reported here for the 2004 United States (USA) component. A total of 3322 Gram-positive cocci were tested by reference broth microdilution methods. Organism species tested included: Staphylococcus aureus (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82% oxacillin-resistant), beta-hemolytic streptococci (241), viridans group streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06-0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the tested streptococci was 0.03 microg/mL. Dalbavancin was more active against tested SSTI pathogens than comparator agents having complete susceptibility rates (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32-fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold) were less active than dalbavancin. In conclusion, dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptides, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared with prior sampled years (2002-2003) in the USA.
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Antibacterianos/farmacología , Infecciones por Bacterias Grampositivas/microbiología , Cocos Grampositivos/efectos de los fármacos , Teicoplanina/análogos & derivados , Farmacorresistencia Bacteriana , Cocos Grampositivos/aislamiento & purificación , Humanos , Control de Infecciones , Pruebas de Sensibilidad Microbiana , Teicoplanina/farmacología , Estados UnidosRESUMEN
Anidulafungin, an echinocandin, is in late stage development for the treatment of fungal infections. We investigated the activity of anidulafungin in combination with other antifungal agents (fluconazole, itraconazole, ketoconazole, amphotericin B and 5-fluorocytosine) against four isolates each of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, and two isolates of Candida krusei using a macrobroth chequerboard method with interactions evaluated by fractional inhibitory concentration indices (FICIs). Additive activity (FICI > 0.5 to 1) or indifference (FICI > 1 to < 4) was observed in 85 of 90 interactions of anidulafungin with another antifungal agent. Synergy with itraconazole (FICI
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Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Candida/efectos de los fármacos , Flucitosina/administración & dosificación , Péptidos Cíclicos/administración & dosificación , Anidulafungina , Animales , Candida/aislamiento & purificación , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Candida glabrata/efectos de los fármacos , Candida glabrata/aislamiento & purificación , Candida tropicalis/efectos de los fármacos , Candida tropicalis/aislamiento & purificación , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Interacciones Farmacológicas , Equinocandinas , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs. METHODS: A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). RESULTS: Infected patients who received weekly dalbavancin (n=33) had an overall success rate (87.0%; 95% confidence interval [CI], 73.2%-100.0%) that was significantly higher than that of those who received vancomycin (n=34) (50.0%; 95% CI, 31.5%-68.5%). Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs. CONCLUSIONS: Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus, including MRSA.
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Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Catéteres de Permanencia/efectos adversos , Teicoplanina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Teicoplanina/efectos adversos , Teicoplanina/uso terapéutico , Vancomicina/efectos adversos , Vancomicina/uso terapéuticoRESUMEN
Dalbavancin, a novel glycopeptide with a long elimination half-life ( approximately 9-12 days), was compared to standard antimicrobial therapy for skin and soft-tissue infections (SSTIs). In a randomized, controlled, open-label, phase 2 proof-of-concept trial, adults received 1100 mg of dalbavancin (as a single intravenous infusion), 1000 mg of dalbavancin intravenously and then 500 mg intravenously 1 week later, or a prospectively defined standard-of-care regimen. A gram-positive pathogen was isolated from samples obtained from 41 (66%) of 62 patients at baseline; Staphylococcus aureus was the most prevalent species (83% of pathogens). Clinical success rates at a follow-up visit (test of cure) were 94.1% among patients treated with 2 doses of dalbavancin, 61.5% among patients treated with 1 dose of dalbavancin, and 76.2% among patients treated with a standard-of-care regimen. All treatment regimens were well tolerated; drug-related adverse reaction rates were similar across the 3 groups. These findings suggest that a regimen of 2 doses of dalbavancin administered 1 week apart is effective in the treatment of complicated, gram-positive bacterial SSTIs and warrants further study.
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Antiinfecciosos/uso terapéutico , Glicopéptidos/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Adulto , Antiinfecciosos/efectos adversos , Tolerancia a Medicamentos , Femenino , Glicopéptidos/efectos adversos , Humanos , Masculino , Enfermedades Cutáneas Infecciosas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Staphylococcus aureus , Teicoplanina/análogos & derivados , Resultado del TratamientoRESUMEN
Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in 601 patients with endoscopically and microbiologically documented esophageal candidiasis. Patients received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found to be statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratory parameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazole for the treatment of esophageal candidiasis, when assessed at the completion of therapy.
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Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Enfermedades del Esófago/microbiología , Fluconazol/uso terapéutico , Péptidos Cíclicos/uso terapéutico , Administración Oral , Adulto , Anciano , Anidulafungina , Antifúngicos/administración & dosificación , Método Doble Ciego , Equinocandinas , Enfermedades del Esófago/tratamiento farmacológico , Femenino , Fluconazol/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/administración & dosificaciónRESUMEN
Resistance to rifampicin (RIF) is a broad subject covering not just the mechanism of clinical resistance, nearly always due to a genetic change in the ß subunit of bacterial RNA polymerase (RNAP), but also how studies of resistant polymerases have helped us understand the structure of the enzyme, the intricacies of the transcription process and its role in complex physiological pathways. This review can only scratch the surface of these phenomena. The identification, in strains of Escherichia coli, of the positions within ß of the mutations determining resistance is discussed in some detail, as are mutations in organisms that are therapeutic targets of RIF, in particular Mycobacterium tuberculosis. Interestingly, changes in the same three codons of the consensus sequence occur repeatedly in unrelated RIF-resistant (RIF(r)) clinical isolates of several different bacterial species, and a single mutation predominates in mycobacteria. The utilization of our knowledge of these mutations to develop rapid screening tests for detecting resistance is briefly discussed. Cross-resistance among rifamycins has been a topic of controversy; current thinking is that there is no difference in the susceptibility of RNAP mutants to RIF, rifapentine and rifabutin. Also summarized are intrinsic RIF resistance and other resistance mechanisms.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Rifampin/farmacología , Animales , ARN Polimerasas Dirigidas por ADN/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Rifabutina/farmacología , Rifampin/análogos & derivadosRESUMEN
Glycine receptor function mediates most inhibitory neurotransmission in the brainstem and spinal cord and is enhanced by alcohols, volatile anesthetics, inhaled drugs of abuse, and endogenous compounds including zinc. Because zinc exists ubiquitously throughout the brain, investigations of its effects on the enhancement of GlyR function by alcohols and anesthetics are important to understanding the effects of these agents in vivo. In the present study, the effects of zinc plus ethanol, pentanol, or isoflurane were tested on homomeric alpha1 glycine receptors to determine if concurrent applications of physiological concentrations of zinc with each of these modulators changed the magnitude of their effects. Homomeric alpha1 glycine receptors were expressed in Xenopus laevis oocytes, and the two-electrode voltage-clamp technique was used to measure glycine-mediated currents in the presence of combinations of zinc with ethanol, pentanol or isoflurane. The combined effects of zinc plus ethanol were greater than the sum of the effects produced by either compound alone. However, this was not seen when zinc was combined with either pentanol or isoflurane. Chelation of zinc by tricine decreased the effects of sub-maximal, but not maximal, concentrations of glycine, and diminished the magnitude of ethanol enhancement observed. These findings suggest a zinc/ethanol interaction at the alpha1 GlyR that results in the enhancement of the effects of ethanol action on GlyR function.
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Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Potenciales de la Membrana/fisiología , Receptores de Glicina/metabolismo , Zinc/farmacología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Estimulación Eléctrica/métodos , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Microinyecciones/métodos , Oocitos , Técnicas de Placa-Clamp , Receptores de Glicina/genética , Análisis Espectral/métodos , XenopusRESUMEN
BACKGROUND: Azole-refractory mucosal candidiasis is a debilitating disease frequently seen in patients who are immunosuppressed as a result of HIV, malignancy, posttransplant immunosuppressive therapy, persistent neutropenia, steroid use, or diabetes. Anidulafungin has potent activity against a broad spectrum of Candida species, including strains resistant to azoles and amphotericin B. We performed an open-label, noncomparative study to examine efficacy and safety of anidulafungin in patients with azole-refractory oropharyngeal and esophageal candidiasis. METHODS: Patients enrolled met diagnostic criteria for azole-refractory mucosal candidiasis. They received intravenous anidulafungin 100 mg on day 1 followed by daily 50-mg doses on day 2 through day 14 or for a maximum of 21 days. Primary efficacy variables were clinical response (for oropharyngeal candidiasis) and endoscopic and clinical response (for esophageal candidiasis) at the end of therapy. RESULTS: Nineteen patients were enrolled; 89% had advanced HIV infection. Clinical success was observed in 95% of patients at end of therapy, and endoscopic success was observed in 92% of patients with esophageal candidiasis. At follow-up, clinical success was maintained in 47% of patients. The most common adverse event, experienced by 4 patients, was nausea and/or vomiting. CONCLUSIONS: Anidulafungin was well tolerated and efficacious in the treatment of patients with azole-refractory esophageal and oropharyngeal candidiasis.
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Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antifúngicos/uso terapéutico , Candidiasis Bucal/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Equinocandinas/uso terapéutico , Enfermedades del Esófago/tratamiento farmacológico , Membrana Mucosa , Adulto , Anidulafungina , Azoles/uso terapéutico , Candidiasis/complicaciones , Farmacorresistencia Fúngica , Equinocandinas/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in humans and offers promise for a convenient weekly dosing regimen. We studied the in vitro bactericidal activity of dalbavancin against target organisms, using the concentrations that are maintained in human blood with the proposed dosage regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were