RESUMEN
BACKGROUND: Under certain circumstances, clinicians treating patients with isavuconazole for invasive aspergillosis or mucormycosis may use therapeutic drug monitoring. However, the accuracy and reproducibility of the various assays used by different laboratories for the quantification of isavuconazole plasma concentrations have yet to be determined. METHODS: Human plasma samples spiked with known concentrations of isavuconazole were provided to 27 European laboratories that took part in a "round-robin" test (an interlaboratory test performed independently at least 2 times; 2 rounds performed in the current study). Assay methods included liquid chromatography-tandem mass spectrometry (LC-MS/MS), LC with ultraviolet detection (LC-UV), LC with fluorescence detection (LC-FL), and bioassay. The accuracy and reproducibility compared with the known concentrations for each sample in each round were compared overall, between assays, and between laboratories. RESULTS: Twenty-seven laboratories participated in the study (LC-MS/MS, n = 15; LC-UV; n = 9; LC-FL, n = 1; bioassay, n = 2). In round 1, for nominal concentrations of 1000, 1700, 2500, and 4000 ng/mL, the mean (SD) determined concentrations were 1007 (183), 1710 (323), 2528 (540), and 3898 (842) ng/mL, respectively. In round 2, for nominal concentrations of 1200, 1800, 2400, and 4000 ng/mL, the mean (SD) determined concentrations were 1411 (303), 2111 (409), 2789 (511), and 4723 (798) ng/mL, respectively. Over both rounds, determined concentrations were consistently within 15% of the nominal concentrations for 10 laboratories (LC-MS/MS, n = 4; LC-UV, n = 5; bioassay, n = 1) and consistently exceeded the upper 15% margin for 7 laboratories (LC-MS/MS and LC-UV, n = 3 each; LC-FL, n = 1). CONCLUSIONS: Alignment of methodologies among laboratories may be warranted to improve the accuracy and reproducibility of therapeutic drug measurements.
Asunto(s)
Bioensayo/métodos , Nitrilos/sangre , Plasma/química , Piridinas/sangre , Triazoles/sangre , Cromatografía Liquida/métodos , Monitoreo de Drogas/métodos , Europa (Continente) , Humanos , Laboratorios , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
To relieve the dryness of atopic dermatitis skin, a lipid formulation of fusidic acid and betamethasone 17-valerate (Fucicort Lipid cream) was developed as an additional treatment option to the established Fucicort cream. The two formulations were compared in patients with clinically infected atopic dermatitis. A total of 629 patients were randomized to twice daily double-blind treatment for 2 weeks with either Fucicort Lipid cream, Fucicort cream, or the new lipid cream vehicle. Clinical assessment was based on a Total Severity Score of the eczematous lesions. Bacteriological samples were taken at inclusion and at subsequent visit(s) if clinically infected lesions persisted. At the end of treatment, the mean reduction in Total Severity score was 82.9% in the lipid cream group, 82.7% in the cream group, and 33.0% in the vehicle group. The percentage of patients with a successful bacteriological response was 89.7%, 89.6% and 25.0%, respectively. Thus, the clinical and anti-bacterial effect of the lipid cream was found to be similar to that of the established cream formulation, and significantly better than that of the vehicle. The new lipid formulation, therefore, offers an efficient, safe and well-tolerated alternative for the short-term treatment of clinically infected atopic dermatitis.
Asunto(s)
Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Valerato de Betametasona/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Ácido Fusídico/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Administración Tópica , Adulto , Dermatitis Atópica/complicaciones , Femenino , Humanos , Masculino , Estudios Prospectivos , Seguridad , Enfermedades Cutáneas Infecciosas/complicaciones , Resultado del TratamientoRESUMEN
Fusidic acid-resistant epidemic Staphylococcus aureus strains causing impetigo bullosa have been reported in Scandinavia. We show that these strains form part of a European epidemic clonotype that carries the fusB determinant. In contrast, resistance to fusidic acid in a collection of nonepidemic strains resulted primarily from mutations in fusA.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Ácido Fusídico/farmacología , Factor G de Elongación Peptídica/genética , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Cartilla de ADN , ADN Bacteriano/genética , Farmacorresistencia Bacteriana , Electroforesis en Gel de Campo Pulsado , Europa (Continente)/epidemiología , Genes Bacterianos/genética , Humanos , Impétigo/microbiología , Pruebas de Sensibilidad Microbiana , Familia de Multigenes , Mutación/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Infecciones Estafilocócicas/epidemiologíaRESUMEN
A novel fusidic acid type antibiotic having the side chain linked to the tetracyclic ring system via a spiro-cyclopropane system is described. 17S,20S-Methanofusidic acid is obtained by an efficient synthetic route including cyclopropanation of the Delta17(20) bond with attack solely from the least hindered alpha-face. The spiro-cyclopropane system orients the side chain into a bioactive conformational space. The new 17S,20S-methanofusidic acid exerts antibacterial activity against several Gram-positive species with potency essentially equal to natural fusidic acid.