Correlation of Moxifloxacin Concentration, C-Reactive Protein, and Inflammatory Cytokines on QTc Interval in Rifampicin-Resistant Tuberculosis Patients Treated with Shorter Regimens

Tutik Kusmiati, Ni Made Mertaniasih, Johanes Nugroho Eko Putranto, Budi Suprapti, Nadya Luthfah, Soedarsono Soedarsono, Winariani Koesoemoprodjo, Aryani Prawita Sari


Background: Drug-resistant tuberculosis (DR-TB) is a global health concern. QTc prolongation is a serious adverse effect in DR-TB patients receiving a shorter regimen. This study aimed to evaluate the correlation of moxifloxacin concentration, CRP, and inflammatory cytokines with QTc interval in DR-TB patients treated with a shorter regimen. Methods: This study was performed in 2 groups of rifampicin-resistant (RR-TB) patients receiving shorter regimens. Correlation for all variables was analyzed. Results: CRP, IL-1β, and QTc baseline showed significant differences between 45 RR-TB patients on intensive phase and continuation phase with p-value of <0.001, 0.040, and <0.001, respectively. TNF-α and IL-6 between RR-TB patients on intensive phase and continuation phase showed no significant difference with p=0.530 and 0.477, respectively. CRP, TNF-α, IL-1 β, and IL-6 did not correlate with QTc interval in intensive phase (p=0.226, 0.281, 0.509, and 0.886, respectively), and also in continuation phase (0.805, 0.865, 0.406, 0.586, respectively). At 2 hours after taking the 48th-dose, moxifloxacin concentration did not correlate with QTc interval, both in intensive phase (p=0.576) and in continuation phase (p=0.691). At 1 hour before taking the 72nd-hour dose, moxifloxacin concentration also did not correlate with QTc interval in intensive phase (p=0.531) and continuation phase (p=0.209). Conclusion: Moxifloxacin concentration, CRP, and inflammatory cytokines did not correlate with QTc interval in RR-TB patients treated with shorter regimens. The use of moxifloxacin is safe but should be routinely monitored and considered the presence of other risk factors for QTc prolongation in RR-TB patients who received shorter regimens.


pulmonology; tropical disease; infection


World Health Organization. Global Tuberculosis Report. Geneva: World Health Organization; 2020.

World Health Organization. WHO Treatment Guidelines for Drug-Resistant Tuberculosis: 2016 Update. Geneva: World Health Organization; 2016.

Indonesian Ministry of Health. Technical Guideline for Drug-Resistant Tuberculosis Treatment with Shorter Regimens in Health Care Facility. Jakarta: Indonesian Ministry of Health; 2017.

Soedarsono S, Kusmiati T, Wulaningrum PA, et al. Factors Cause of Switching Shorter Regimen to Longer Regimen in Multidrug-Resistant/ Rifampicin-Resistant Tuberculosis Treated Patients in Dr. Soetomo Hospital Surabaya, Indonesia. Indian J Med Forensic Med Toxicol 2021; 15: 1589-1595.

Kusmiati T, Mertaniasih NM, Putranto JN, et al. Factors that Contribute to the QTc Interval Prolongation in DR-TB Patients on STR Regimen. Indian J Med Forensic Med Toxicol 2020; 15: 1618-1625.

Khan F, Ismail M, Khan Q, Ali Z. Moxifloxacin-induced QT interval prolongation and torsades de pointes: a narrative review. Expert Opin Drug Saf 2018; 17(10).

Lazzerini PE, Laghi-Pasini F, Bertolozzi I, Morozzi G, Lorenzini S, Simpatico A, et al. Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes. Heart (British Cardiac Society) 2017; 103 (22):1821-1829. doi:10.1136/heartjnl-2016-311079.

Lazzerini PE, Capecchi PL, El- Sherif N, Pasini FL, Boutjdir M. Emerging Arrhythmic Risk of Autoimmune and Inflammatory Cardiac Channelopathies. J Am Heart Assoc 2018; 7: e010595. Doi: 10.1161/JAHA.118.010595.

Kim E, Joo S, Kim J, Ahn J, Kim J, et al. Association between C-reactive protein and QTc interval in middle-aged men and women. Eur J Epidemiol 2006; 21(9): 653–659.

Sproston NR, Ashworth. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol 2018; 9: 754.

Pansey P, Shukla S, Acharya S. Serum C-reactive protien (CRP) - a dependent prognostic marker in pulmonary tuberculosis. International Journal of Contemporary Medical Research 2017;4(10):2111-2114.

Xie Y, Mai JT, Wang F, Lin YQ, Yuan WL, Luo NS, Fang MC, Wang JF, Chen YX. Effects of C-reactive protein on K+ channel interaction protein 2 in cardiomyocytes. Am J Trans Res 2015; 7(5): 922-931.

Yoon HY, Jo KW, Nam GB, Shim TS. Clinical significance of QT-prolonging drug use in patients with MDR-TB or NTM disease. Int J Tuberc Lung Dis 2017; 21(9): 996-1001.

United States Agency for International Development. Guide for QTc monitoring and management of drug-resistant TB patients with QT-prolonging agents. New York: USAID; 2018.

Indonesian Ministry of Health. Technical Guideline for Programmatic Management of Drug Resistant Tuberculosis. Jakarta: Indonesian Ministry of Health; 2014.

Indonesian Ministry of Health. Guidelines for Drug-Resistant Tuberculosis Management in Health Care Facility. Jakarta: Indonesian Ministry of Health; 2019.

Weyer K. Multidrug-Resistant Tuberculosis. CME 2005; 23(2): 74-84.

Brode SK, Varadi R, McNamee J, Malek N, Stewart S, Jamieson FB, et al. Can Respir J 2015; 22(2): 97-102.

Migliori GB, Tiberi S, Zumla A, Petersen E, Chakaya JM, Wejse C, et al. MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network. Int J Infect Dis 2020; 92S: S15-S25.

Kusmiati T, Suci YD, Dewi KP, et al. QTc Interval Prolongation in Drug Resistant Tuberculosis Patients Treated with Shorter Treatment Regimens. Med Leg J Update 2021; 21: 1208-1215.

Chang KT, Shu HS, Chu CY, Lee WH, Hsu PC, Du HM, et al. Association between C-reactive protein, corrected QT interval and presence of QT prolongation in hypertensive patients. Kaohsiung Journal of Medical Sciences 2014; 30: 310-5.

Kobayashi H, Kobayashi Y, Yokoe I, Kitamura N, Nishiwaki A, Takei M, et al. Heart rate–corrected QT interval duration in rheumatoid arthritis and its reduction with treatment with the interleukin 6 inhibitor tocilizumab. J Rheumatol 2018;45:1620-7.

Panoulas VF, Toms TE, Douglas KM, Sandoo A, Metsios GS, Kalinoglou AS, et al. Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid arthritis: an association driven by high inflammatory burden. Rheumatology 2014;53:131-7.

Medenwald D., Kors JA, Loppnow H, Thiery J, Kluttig A, Nuding S, et al. Inflammation and Prolonged QT Time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. PLoS ONE 2014; 9(4):e95994.

Pisoni CN, Reina S, Arakaki D, Eimon A, Carrizo C, Borda E. Elevated IL-1beta levels in anti-Ro/SSA connective tissue diseases patients with prolonged corrected QTc interval. Clin Exp Rheumatol 2015; 33(5): 715–20.

Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation 2004; 109[suppl II]:II-2–II-10.).

Soedarsono S, Subiantoro MC. Changes of CRP serum levels in pulmonary TB patients with AFB smear-positive sputum before and two months after receiving anti-tuberculosis drug treatment. Indian J Tuberc 2019; 66: 134-8.

Romero-Adrian TB, Leal-Montiel J, Fernandez G, Valecillo A. Role of Cytokines and Other Factors Involved in the Mycobacterium tuberculosis Infection. World J Immunol 2015; 5(1): 16-50.

Chandrashekara S. C - reactive protein: An inflammatory marker with specific role in physiology, pathology, and diagnosis. IJRCI 2014; 2(S1): SR3. DOI: 10.15305/ijrci/v2iS1/117.

Aromolaran AS, Srivastava U, Ali A, Chahine M, Lazaro D, El-Sherif N, et al. Interleukin-6 inhibition of hERG underlies risk for acquired long QT in cardiac and systemic inflammation. PloS ONE 2018; 13(12): e0208321.

Watson KJ, Gorczyca WP, Umland J, et al. Pharmacokinetic–pharmacodynamic modelling of the effect of Moxifloxacin on QTc prolongation in telemetered cynomolgus monkeys. J Pharmacol Toxicol Methods 2011; 63: 304-313.

Nachimutu S, Assar MD, Schussler JM. Drug-Induced QT Interval Prolongation: Mechanisms and Clinical Management. Ther Adv Drug Saf 2012; 3: 241-253.

Cubeddu, L. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias. Curr Cardiol Rev 2016; 12: 141-154.

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