Potentially High Number of Ineffective Drugs with the Standard Shorter Course Regimen for Multidrug-Resistant Tuberculosis Treatment in Haiti

Abstract

Multidrug-resistant tuberculosis (MDR-TB) outcomes are poor partly because of the long treatment duration; the World Health Organization conditionally recommends a shorter course regimen to potentially improve treatment outcomes. Here, we describe the drug susceptibility patterns of a cohort of MDR-TB patients in Haiti and determine the number of likely effective drugs if they were treated with the recommended shorter course regimen. We retrospectively examined drug susceptibility patterns of adults initiating MDR-TB treatment between 2008 and 2015 at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections in Port-au-Prince, Haiti. First-and second-line drug susceptibility testing (DST) was analyzed and used to determine the number of presumed effective drugs. Of the 239 patients analyzed, 226 (95%), 183 (77%), 135 (57%), and 38 (16%) isolates were resistant to high-dose isoniazid, ethambutol, pyrazinamide, and ethionamide, respectively. Eight patients (3%) had resistance to either a fluoroquinolone or a second-line injectable and none had extensively resistant TB. Of the 239 patients, 132 (55%) would have fewer than five likely effective drugs in the intensive phase of the recommended shorter course regimen and 121 (51%) would have two or fewer likely effective drugs in the continuation phase. Because of the high rates of resistance to first-line TB medications, about 50% of MDR-TB patients would be left with only two effective drugs in the continuation phase of the recommended shorter course regimen, raising concerns about the effectiveness of this regimen in Haiti and the importance of using DST to guide treatment.

Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis

“…These associations were not statistically significant, albeit the trial was not powered for each outcome. Second, because the shorter regimen is standardised, whether it is effective in the face of resistance to its component medications has remained a matter of debate [5][6][7][8][9][10]. The WHO recommendation against use of the shorter regimen in the presence of resistance to any of its component medications has been questioned as being too restrictive [8,11].…”

What’s Next for the Standard Short-Course Regimen for Treatment of Multidrug-Resistant Tuberculosis

“…In this issue of the AJTMH , Walsh et al report high rates of resistance to several drugs used in the STR based on drug susceptibility testing (DST) of isolates from 239 consecutive MDR-TB patients diagnosed between 2008 and 2015 at the GHESKIO clinic in Haiti. 4 They found resistance in 95% of patients to high-dose isoniazid, 57% to pyrazinamide, 77% to ethambutol, and 16% to ethionamide. Very few isolates were resistant to fluoroquinolones or second-line injectables (3%), and few patients had previous exposure to SLD (0.4%), which are considered contraindications for use of the STR in current WHO recommendations.…”