SETTING: Tuberculosis Centre, University Medical Centre, Groningen, The Netherlands. OBJECTIVES: To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and minimal inhibitory concentration (MIC). DESIGN: Intralesional concentrations were measured 2 h after drug administration (six pleural effusions, 10 psoas abscesses). RESULTS: A wide range of concentrations was found for pleural effusions and psoas abscesses. Concentrations were below MIC values in none of 15 patients for INH, in two of 13 for RMP, and in eight of nine for PZA. The Cmax:MIC ratio was always >4 for INH, in four of 13 for RMP, and in none of nine for PZA. In 5/8 patients receiving all three drugs, both RMP and PZA had Cmax:MIC ratios <4, indicating sub-therapeutic drug levels. CONCLUSION: Penetration of INH was always sufficient, penetration of RMP mostly below the desired ratio, and for PZA on average 10 times too low. Five of eight patients on all three drugs had Cmax:MIC ratios <4. This indicates intralesional sub-therapeutic drug levels for RMP and PZA, and local monotherapy with INH. This could induce drug resistance. Drainage as additional therapy seems indicated.
SETTING:Tuberculosis Centre, University Medical Centre, Groningen, The Netherlands. OBJECTIVES: To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and minimal inhibitory concentration (MIC). DESIGN: Intralesional concentrations were measured 2 h after drug administration (six pleural effusions, 10 psoas abscesses). RESULTS: A wide range of concentrations was found for pleural effusions and psoas abscesses. Concentrations were below MIC values in none of 15 patients for INH, in two of 13 for RMP, and in eight of nine for PZA. The Cmax:MIC ratio was always >4 for INH, in four of 13 for RMP, and in none of nine for PZA. In 5/8 patients receiving all three drugs, both RMP and PZA had Cmax:MIC ratios <4, indicating sub-therapeutic drug levels. CONCLUSION: Penetration of INH was always sufficient, penetration of RMP mostly below the desired ratio, and for PZA on average 10 times too low. Five of eight patients on all three drugs had Cmax:MIC ratios <4. This indicates intralesional sub-therapeutic drug levels for RMP and PZA, and local monotherapy with INH. This could induce drug resistance. Drainage as additional therapy seems indicated.
Authors: Jaclyn C Flanigan; Lucia B Jilaveanu; Mark Faries; Mario Sznol; Stephan Ariyan; James B Yu; Jonathan P S Knisely; Veronica L Chiang; Harriet M Kluger Journal: Curr Probl Cancer Date: 2011 Jul-Aug Impact factor: 3.187
Authors: Abigail L Manson; Keira A Cohen; Thomas Abeel; Christopher A Desjardins; Derek T Armstrong; Clifton E Barry; Jeannette Brand; Sinéad B Chapman; Sang-Nae Cho; Andrei Gabrielian; James Gomez; Andreea M Jodals; Moses Joloba; Pontus Jureen; Jong Seok Lee; Lesibana Malinga; Mamoudou Maiga; Dale Nordenberg; Ecaterina Noroc; Elena Romancenco; Alex Salazar; Willy Ssengooba; A A Velayati; Kathryn Winglee; Aksana Zalutskaya; Laura E Via; Gail H Cassell; Susan E Dorman; Jerrold Ellner; Parissa Farnia; James E Galagan; Alex Rosenthal; Valeriu Crudu; Daniela Homorodean; Po-Ren Hsueh; Sujatha Narayanan; Alexander S Pym; Alena Skrahina; Soumya Swaminathan; Martie Van der Walt; David Alland; William R Bishai; Ted Cohen; Sven Hoffner; Bruce W Birren; Ashlee M Earl Journal: Nat Genet Date: 2017-01-16 Impact factor: 38.330