Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.
Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.
Authors: N Alsaad; T van der Laan; R van Altena; K R Wilting; T S van der Werf; Y Stienstra; D van Soolingen; J W C Alffenaar Journal: Int J Antimicrob Agents Date: 2013-08-23 Impact factor: 5.283
Authors: Saverio De Lorenzo; Jan Wilem Alffenaar; Giovanni Sotgiu; Rosella Centis; Lia D'Ambrosio; Simon Tiberi; Mathieu S Bolhuis; Richard van Altena; Piero Viggiani; Andrea Piana; Antonio Spanevello; Giovanni Battista Migliori Journal: Eur Respir J Date: 2012-09-20 Impact factor: 16.671
Authors: L Davies Forsman; C G Giske; J Bruchfeld; T Schön; P Juréen; K Ängeby Journal: Antimicrob Agents Chemother Date: 2015-03-30 Impact factor: 5.191
Authors: Kristina Shigyo; Oksana Ocheretina; Yves Mary Merveille; Warren D Johnson; Jean William Pape; Carl F Nathan; Daniel W Fitzgerald Journal: Antimicrob Agents Chemother Date: 2013-03-18 Impact factor: 5.191
Authors: Sander P van Rijn; Marlanka A Zuur; Richard Anthony; Bob Wilffert; Richard van Altena; Onno W Akkerman; Wiel C M de Lange; Tjip S van der Werf; Jos G W Kosterink; Jan-Willem C Alffenaar Journal: Antimicrob Agents Chemother Date: 2019-01-29 Impact factor: 5.191
Authors: Shahin Ranjbar; Viraga Haridas; Aya Nambu; Luke D Jasenosky; Supriya Sadhukhan; Thomas S Ebert; Veit Hornung; Gail H Cassell; James V Falvo; Anne E Goldfeld Journal: iScience Date: 2019-11-06
Authors: Christina Cahill; Dónal J Cox; Fiona O'Connell; Sharee A Basdeo; Karl M Gogan; Cilian Ó'Maoldomhnaigh; Jacintha O'Sullivan; Joseph Keane; James J Phelan Journal: Int J Mol Sci Date: 2021-11-10 Impact factor: 5.923
Authors: Christina Cahill; Fiona O'Connell; Karl M Gogan; Donal J Cox; Sharee A Basdeo; Jacintha O'Sullivan; Stephen V Gordon; Joseph Keane; James J Phelan Journal: Int J Mol Sci Date: 2021-03-13 Impact factor: 5.923