Increased 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

Jeffrey A Tornheim; Zarir F Udwadia; Prerna R Arora; Ishita Gajjar; Samridhi Sharma; Megha Karane; Namrata Sawant; Nisha Kharat; Alexander J Blum; Shri Vijay Bala Yogendra Shivakumar; Akshay N Gupte; Nikhil Gupte; Jai B Mullerpattan; Lancelot M Pinto; Tester F Ashavaid; Amita Gupta; Camilla Rodrigues

doi:10.1093/ofid/ofab615

Increased 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

Open Forum Infect Dis. 2021 Dec 23;9(2):ofab615. doi: 10.1093/ofid/ofab615. eCollection 2022 Feb.

Authors

Jeffrey A Tornheim¹, Zarir F Udwadia², Prerna R Arora³, Ishita Gajjar³, Samridhi Sharma³, Megha Karane³, Namrata Sawant³, Nisha Kharat³, Alexander J Blum⁴, Shri Vijay Bala Yogendra Shivakumar⁵, Akshay N Gupte¹, Nikhil Gupte^{1

5}, Jai B Mullerpattan², Lancelot M Pinto², Tester F Ashavaid³, Amita Gupta^{1

6}, Camilla Rodrigues⁷

Affiliations

¹ Center for Clinical Global Health Education, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Respiratory Medicine, P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India.
³ Department of Laboratory Medicine, P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India.
⁴ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Johns Hopkins University-India Office (Center for Clinical Global Health Education), Pune, Maharashtra, India.
⁶ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁷ Department of Microbiology, P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India.

Abstract

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.

Keywords: India; MDR-TB; drug resistance; drug susceptibility testing; moxifloxacin.