RESUMEN
Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC-MS/MS in 30 study participants-20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA Cmax was 0.4 mg/L-and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.
Asunto(s)
Úlcera de Buruli , Claritromicina , Preparaciones de Acción Retardada , Mycobacterium ulcerans , Rifampin , Humanos , Claritromicina/farmacocinética , Claritromicina/administración & dosificación , Masculino , Femenino , Adulto , Rifampin/farmacocinética , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Persona de Mediana Edad , Úlcera de Buruli/tratamiento farmacológico , Úlcera de Buruli/microbiología , Mycobacterium ulcerans/efectos de los fármacos , Preparaciones de Acción Retardada/farmacocinética , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Anciano , Adulto Joven , Área Bajo la Curva , Espectrometría de Masas en TándemRESUMEN
Buruli ulcer (BU) is a tropical, infectious skin disease. The resulting ulcer can take a long time to heal, and a high standard of wound care is essential. Currently, the only dressing used for BU wound care is gauze, and its removal causes pain and bleeding. We performed a pilot implementation project using HydroTac(®) (HARTMANN, Heidenheim, Germany), a modern dressing combining foam with a hydrogel component. For future BU treatment, we recommend to use a more absorbent dressing than the HydroTac dressing used in the current project. However, we show that modern dressings can be applied to BUs and that HydroTac dressings yield clean, healing wounds, and prevent the pain and bleeding associated with gauze dressings. Wound care is a vital but to date neglected aspect of BU management.
Asunto(s)
Vendajes , Úlcera de Buruli/terapia , Cicatrización de Heridas , Adolescente , Úlcera de Buruli/microbiología , Niño , Ghana , Humanos , Hidrogeles/química , Proyectos PilotoRESUMEN
INTRODUCTION: Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU. METHODS: The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable. RESULTS: Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ(2)), larger lesions (p = .021 by Χ(2)) and genetic factors. The polymorphisms 3'UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms. CONCLUSIONS: Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene.
Asunto(s)
Antiinfecciosos/administración & dosificación , Úlcera de Buruli/tratamiento farmacológico , Úlcera de Buruli/genética , Proteínas de Transporte de Catión/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Úlcera de Buruli/patología , Femenino , Genotipo , Humanos , Masculino , Radioinmunoensayo , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Buruli ulcer (BU) is an infectious skin disease that occurs mainly in West and Central Africa. It can lead to severe disability and stigma because of scarring and contractures. Effective treatment with antibiotics is available, but patients often report to the hospital too late to prevent surgery and the disabling consequences of the disease. In a highly endemic district in Ghana, intensified public health efforts, mainly revolving around training and motivating community-based surveillance volunteers (CBSVs), were implemented. As a result, 70% of cases were reported in the earliest-World Health Organization category I-stage of the disease, potentially minimizing the need for surgery. CBSVs referred more cases in total and more cases in the early stages of the disease than any other source. CBSVs are an important resource in the early detection of BU.
Asunto(s)
Úlcera de Buruli/prevención & control , Vigilancia de la Población , Voluntarios , Úlcera de Buruli/epidemiología , Enfermedades Endémicas , Ghana/epidemiología , HumanosRESUMEN
Buruli ulcer (BU) is a disease affecting the skin, subcutaneous fat, and bone tissues. Wound care is important in the prevention of disabilities. Awareness of current wound care practices in BU-endemic regions is necessary for future wound care interventions. Thirty-one health care workers in Ghana and Benin were interviewed with a semi-structured interview, complemented by structural observations. Quantitative data were analyzed through t tests and one-way analysis of variance, and qualitative data through descriptive statistics. There appeared to be a general understanding of wound assessment. A large variety of different topical antiseptics was reported to be used, pressure irrigation was never reported. Gauze was the main dressing type and a moist environment was preferred, but could not be maintained. Bleeding and pain were observed frequently. Standard of wound care differed importantly between health care personnel and between institutions and adherence to World Health Organization guidelines was low.