TY - JOUR T1 - Shortened multidrug-resistant tuberculosis regimens overcome low-level fluoroquinolone resistance JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00223-2017 VL - 49 IS - 6 SP - 1700223 AU - Armand Van Deun AU - Chen-Yuan Chiang Y1 - 2017/06/01 UR - http://erj.ersjournals.com/content/49/6/1700223.abstract N2 - We read the research letter by Javaid et al. [1] with great interest. The recommendations from the World Health Organization (WHO) on the use of shortened multidrug-resistant tuberculosis (MDR-TB) regimens controversially indicated that “shortened MDR-TB regimens should not be used in patients who have documented or likely resistance to medicines in the regimen” [2], leading to the concept that MDR-TB patients with additional resistance to not only fluoroquinolones (FQs) or second-line injectables (SLIs), but also ethambutol (EMB), prothionamide (Pto) and pyrazinamide (PZA) would not be eligible for the regimens [3]. This is a highly conservative approach that will greatly limit the applicability of shortened MDR-TB regimens and deprive many MDR-TB patients in high-burden countries of short and highly effective regimens. The 9-month MDR-TB regimen piloted in Bangladesh comprised high-dose gatifloxacin (hGfx), clofazimine (Cfz), EMB and PZA throughout, supplemented by kanamycin (Km), Pto and high-dose isoniazid (hINH) during an intensive phase [4]. The regimen was initially designed to be used in settings with limited resources, where drug susceptibility testing was not available in a timely manner. It was designed as a standardised regimen, using clofazimine and first-line drugs to replace toxic and less effective second-line drugs such as cycloserine and para-aminosalicylic acid. The drugs that are crucial in achieving sputum conversion are hGfx and Km, and those crucial in shortening the duration of treatment are hGfx, Cfz and PZA [5]. Other drugs, in combination, play a supportive role and full susceptibility to these drugs was not expected in the original design. Most patients treated with shortened MDR-TB regimens in Bangladesh [4] and other countries [6] have been exposed to EMB for a prolonged period. Those with resistance to EMB were not excluded and replacement of EMB by another drug was not performed. hINH and Pto were combined complimentarily to address cross-resistance to Pto in inhA-mutant strains of Mycobacterium tuberculosis, since the serum level of hINH will exceed the minimum inhibitory concentration (MIC) of strains with inhA mutation by a wide margin, ensuring that at least one of hINH and Pto will be effective in most cases. Resistance to Pto was not associated with an unfavourable outcome [4] and hINH may also be able to suppress a substantial proportion of bacilli with katG mutation.Shortened unmodified MDR-TB regimens using high-dose gatifloxacin overcome low-level fluoroquinolone resistance http://ow.ly/VCHF30bt4kA ER -