Open AccessIncreased Moxifloxacin Dosing Among Patients With Multidrug-Resistant Tuberculosis With Low-Level Resistance to Moxifloxacin Did Not Improve Treatment Outcomes in a Tertiary Care Center in Mumbai, India
Author(s) -
Jeffrey A. Tornheim,
Zarir F Udwadia,
Prerna Arora,
Ishita Gajjar,
Samridhi Sharma,
Megha Karane,
Namrata Sawant,
Nisha Kharat,
Alan Blum,
Shri Vijay Bala Yogendra Shivakumar,
Akshay Gupte,
Nikhil Gupte,
Jai Mullerpattan,
Lancelot Pinto,
Tester F. Ashavaid,
Amita Gupta,
Camilla Rodrigues
Publication year - 2021
Publication title -
open forum infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.546
H-Index - 35
ISSN - 2328-8957
DOI - 10.1093/ofid/ofab615
Subject(s) - moxifloxacin , medicine , hazard ratio , regimen , isoniazid , tuberculosis , cohort , drug resistance , culture conversion , rifabutin , confidence interval , antibiotics , sputum , microbiology and biotechnology , clarithromycin , pathology , helicobacter pylori , biology
Background Mycobacterium tuberculosis (Mtb) strains resistant to isoniazid and rifampin (multidrug-resistant tuberculosis [MDR-TB]) are increasingly reported worldwide, requiring renewed focus on the nuances of drug resistance. Patients with low-level moxifloxacin resistance may benefit from higher doses, but limited clinical data on this strategy are available. Methods We conducted a 5-year observational cohort study of MDR-TB patients at a tertiary care center in India. Participants with Mtb isolates resistant to isoniazid, rifampin, and moxifloxacin (at the 0.5 µg/mL threshold) were analyzed according to receipt of high-dose moxifloxacin (600 mg daily) as part of a susceptibility-guided treatment regimen. Univariable and multivariable Cox proportional hazard models assessed the relationship between high-dose moxifloxacin and unfavorable treatment outcomes. Results Of 354 participants with MDR-TB resistant to moxifloxacin, 291 (82.2%) received high-dose moxifloxacin. The majority experienced good treatment outcomes (200 [56.5%]), which was similar between groups (56.7% vs 54.0%, P = .74). Unfavorable outcomes were associated with greater extent of radiographic disease, lower initial body mass index, and concurrent treatment with fewer drugs with confirmed phenotypic susceptibility. Treatment with high-dose moxifloxacin was not associated with improved outcomes in either unadjusted (hazard ratio [HR], 1.2 [95% confidence interval {CI}, .6–2.4]) or adjusted (HR, 0.8 [95% CI, .5–1.4]) models but was associated with joint pain (HR, 3.2 [95% CI, 1.2–8.8]). Conclusions In a large observational cohort, adding high-dose (600 mg) moxifloxacin to a drug susceptibility test–based treatment regimen for MDR-TB was associated with increased treatment-associated side effects without improving overall outcomes and should be avoided for empiric treatment of moxifloxacin-resistant MDR-TB.