TY - JOUR
T1 - 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
AU - Tornheim, Jeffrey A.
AU - Udwadia, Zarir F.
AU - Arora, Prerna R.
AU - Gajjar, Ishita
AU - Sharma, Samridhi
AU - Karane, Megha
AU - Sawant, Namrata
AU - Kharat, Nisha
AU - Blum, Alexander J.
AU - Shivakumar, Shri Vijay Bala Yogendra
AU - Gupte, Akshay N.
AU - Gupte, Nikhil
AU - Mullerpattan, Jai B.
AU - Pinto, Lancelot M.
AU - Ashavaid, Tester F.
AU - Gupta, Amita
AU - Rodrigues, Camilla
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - India
KW - MDR-TB
KW - drug resistance
KW - drug susceptibility testing
KW - moxifloxacin
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U2 - 10.1093/ofid/ofab615
DO - 10.1093/ofid/ofab615
M3 - Article
C2 - 35097152
AN - SCOPUS:85124909717
SN - 2328-8957
VL - 9
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 2
M1 - ofab615
ER -