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1.
Pediatr Pulmonol ; 54(7): 984-992, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30854795

RESUMEN

BACKGROUND: Despite the significant impact of chronic symptoms on quality of life with cystic fibrosis (CF), the role of palliative care in management of this disease is not well defined. The coping, goal assessment, and relief from evolving CF symptoms (CF-CARES) model is a primary palliative care intervention designed to provide chronic symptom management at all stages of the disease. The goal of this pilot study was to estimate the effectiveness of the CF-CARES intervention on improving chronic symptoms and quality of life for people living with CF. METHODS: A structured assessment was used to guide referral to supportive services intended to address burdensome symptoms. Follow-up assessments were performed approximately 3 and 6 months later. Longitudinal regression analyses of changes in symptoms and quality of life were performed for all participants regardless of utilization of supportive services. Subgroup analyses were performed for subjects participating in mental health and alternative health services. RESULTS: Forty-one subjects completed assessment and referral processes. The mean number of CF-associated symptoms decreased over time, as did respiratory symptom-related distress and depressive symptoms. Subjects utilizing alternative health services reported less psychological distress at follow-up. Among subjects with severe disease, mental health, and quality of life improved, especially for those using mental health services. CONCLUSIONS: The CF-CARES model resulted in significant mental health and quality-of-life benefits, suggesting the value of integrating symptom management interventions into routine CF care. Moreover, mental health services can play a key role in CF-specific primary palliative care, especially for those with advanced disease.


Asunto(s)
Fibrosis Quística/psicología , Cuidados Paliativos , Atención Primaria de Salud , Calidad de Vida , Adaptación Psicológica , Adolescente , Adulto , Depresión , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Proyectos Piloto , Adulto Joven
2.
Artículo en Inglés | MEDLINE | ID: mdl-28923873

RESUMEN

Bacterial persisters are a quasidormant subpopulation of cells that are tolerant to antibiotic treatment. The combination of the aminoglycoside tobramycin with fumarate as an antibacterial potentiator utilizes an antipersister strategy that is aimed at reducing recurrent Pseudomonas aeruginosa infections by enhancing the killing of P. aeruginosa persisters. Stationary-phase cultures of P. aeruginosa were used to generate persister cells. A range of tobramycin concentrations was tested with a range of metabolite concentrations to determine the potentiation effect of the metabolite under a variety of conditions, including a range of pH values and in the presence of azithromycin or cystic fibrosis (CF) patient sputum. In addition, 96-well dish biofilm and colony biofilm assays were performed, and the cytotoxicity of the tobramycin-fumarate combination was determined utilizing a lactate dehydrogenase (LDH) assay. Enhanced killing of up to 6 orders of magnitude of P. aeruginosa persisters over a range of CF isolates, including mucoid and nonmucoid strains, was observed for the tobramycin-fumarate combination compared to killing with tobramycin alone. Furthermore, significant fumarate-mediated potentiation was seen in the presence of azithromycin or CF patient sputum. Fumarate also reduced the cytotoxicity of tobramycin-treated P. aeruginosa to human epithelial airway cells. Finally, in mucoid and nonmucoid CF isolates, complete eradication of P. aeruginosa biofilm was observed in the colony biofilm assay due to fumarate potentiation. These data suggest that a combination of tobramycin with fumarate as an antibacterial potentiator may be an attractive therapeutic for eliminating recurrent P. aeruginosa infections in CF patients through the eradication of bacterial persisters.


Asunto(s)
Antibacterianos/farmacología , Fumaratos/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/farmacología , Azitromicina/farmacología , Biopelículas/crecimiento & desarrollo , Fibrosis Quística , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/microbiología , Esputo/química , Esputo/microbiología
3.
J Surg Res ; 183(2): 767-76, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23478086

RESUMEN

BACKGROUND: Cutaneous thermal injuries (i.e., burns) remain a common form of debilitating trauma, and outcomes are often worsened by wound infection with environmental bacteria, chiefly Pseudomonas aeruginosa. MATERIALS AND METHODS: We tested the effects of early administration of a single dose of azithromycin, with or without subsequent antipseudomonal antibiotics, in a mouse model of standardized thermal injury infected with P aeruginosa via both wound site and systemic infection. We also tested the antimicrobial effects of these antibiotics alone or combined in comparative biofilm and planktonic cultures in vitro. RESULTS: In our model, early azithromycin administration significantly reduced wound and systemic infection without altering wound site or circulating neutrophil activity. The antimicrobial effect of azithromycin was additive with ciprofloxacin but significantly reduced the antimicrobial effect of tobramycin. This pattern was reproduced in biofilm cultures and not observed in planktonic cultures of P aeruginosa. CONCLUSION: These data suggest that early administration of azithromycin following burn-related trauma and infection may reduce P aeruginosa infection and potential interactions with other antibiotics should be considered when designing future studies.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Quemaduras/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Infección de Heridas/microbiología , Animales , Ciprofloxacina/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Masculino , Ratones , Tobramicina/uso terapéutico , Resultado del Tratamiento , Infección de Heridas/tratamiento farmacológico
4.
Pediatr Pulmonol ; 46(2): 184-92, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20963843

RESUMEN

RATIONALE: In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways. METHODS: A multicenter randomized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinically stable adolescent and adult CF patients. Thirty-nine participants were randomized to biofilm or conventional treatment groups; 14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results. RESULTS: Of the agents tested, meropenem was most active against biofilm-grown bacteria, and was included in regimens for about half of each study group. For 19 of 39 randomized participants, randomization to the other study group would not have changed the antibiotic classes of the assigned regimen. Study groups were comparable at baseline, and had similar mean decreases in bacterial density, measured in log(10) colony forming units per gram of sputum (biofilm, -2.94 [SD 2.83] vs. conventional, -3.27 [SD 3.09]), and mean increases in forced expiratory volume in 1 sec, measured in liters (0.18 [SD 0.20] vs. 0.12 [SD 0.22]). CONCLUSIONS: In this pilot study, antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses. The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation.


Asunto(s)
Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Fibrosis Quística/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Adulto , Fibrosis Quística/complicaciones , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Quimioterapia Combinada , Femenino , Flujo Espiratorio Forzado , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Meropenem , Pruebas de Sensibilidad Microbiana/métodos , Proyectos Piloto , Infecciones del Sistema Respiratorio/microbiología , Esputo/efectos de los fármacos , Esputo/microbiología , Tienamicinas/uso terapéutico , Adulto Joven
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