19Acta Med Indones - Indones J Intern Med • Vol 54 • Number 1 • January 2022

ORIGINAL ARTICLE

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

Tutik Kusmiati1,2, Ni Made Mertaniasih3*, Johanes Nugroho Eko Putranto4,
Budi Suprapti5, Nadya Luthfah4, Soedarsono2, Winariani Koesoemoprodjo2,
Aryani Prawita Sari2

1 Doctoral Program of Medical Science, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia.
2 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine Universitas Airlangga, Surabaya,

Indonesia.
3 Department of Clinical Microbiology, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia.
4 Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga, Surabaya,

Indonesia.
5 Department of Clinical Pharmacy, Faculty of Pharmacy Universitas Airlangga, Surabaya, Indonesia.

*Corresponding Author:
Ni Made Mertaniasih, MD. Department of Clinical Microbiology, Faculty of Medicine Universitas Airlangga. Jl.
Mayjen Prof. Dr. Moestopo No. 47, Surabaya, Indonesia. Email: nmademertaniasih@gmail.com.

ABSTRACT
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.

Keywords: Drug-resistant Tuberculosis, shorter treatment regimen, QTc interval.

Tutik Kusmiati Acta Med Indones-Indones J Intern Med

INTRODUCTION
Tuberculosis (TB) caused by Mycobacterium

tuberculosis strains resistant to anti-TB drugs
is becoming a global health concern with an
increasing number of cases. World Health
Organization (WHO) reported 465,000 cases of
Drug-Resistant Tuberculosis (DR-TB) in 2020
with a treatment success rate of 57%. Indonesia
currently ranks 5th for countries with high DR-TB
cases with a treatment success rate of less than
50%, due to the high mortality rate and loss to
follow-up.1 In 2016, the WHO recommended a
standardized shorter regimen off 9-12 months to
treat Multidrug-Resistant/Rifampicin-Resistant
(MDR/RR-TB) patients with a specific inclusion
criteria.2 Indonesia started to implement the
shorter regimen in 2017.3 However, not all
MDR/RR-TB patients were treated with shorter
regimens until the end of treatment and 16/224
(7%) of patients switched their regimens from
shorter regimen to individual regimens due to
the presence of prolonged QT.4 Another study
reported the incidence of increased QTc interval
of >30 ms in 21/98 (21.4%) and >60 ms in 10/98
(10.2%) of DR-TB patients who received shorter
regimens.5 Interval QT prolongation is a serious
adverse effect and can potentially cause Torsade
de Pointes (TdP) and sudden cardiac death.6
Moxifloxacin is one of the components of shorter
regimen and is often criticized for its higher
risk of QTc interval prolongation and TdP.[4,6]
According to the national program, moxifloxacin
was given in 400 mg, 600 mg, or 800 mg dosages
based on body weight.3

Inflammatory activation due to systemic
inflammation was indicated as a new potential
cause of acquired long QT syndrome via
cytokine-mediated changes in cardiomyocyte
ion channels.7 Impaired expression and or
function of several cardiac ion channels was
affected by systemically or locally released
inflammatory cytokines (mainly TNF-α, IL-
1, and IL-6), resulting in a decrease of K+
currents and or an increase of ICaL. Cardiac or
systemic inflammation promotes QTc-interval
prolongation via cytokine-mediated effects,
and this may increase sudden cardiac death
risk.8

C-reactive protein (CRP) is one of the acute
phase proteins that increases during systemic
inflammation.9,10 It is also commonly used as
a prognostic marker in TB.11 Elevated CRP
serum level is a strong independent predictor
of heart disease and cardiovascular disease
in asymptomatic individuals.9,10 Xie et al.
(2015) suggested that CRP may directly or
indirectly influence QTc interval via influencing
the expression of K+ channel interaction
protein 2 (KChIP2) and formation of transient
outward potassium current (Ito.f) density of
cardiomyocytes.12

P r o l o n g a t i o n o f Q Tc i n t e r v a l i s
usually asymptomatic and requires routine
electrocardiography (ECG) monitoring during
treatment using QT-prolonging drug.2,13 Hence,
it is very important to thoroughly assess DR-TB
patients before attributing QTc prolongation
solely due to anti-TB drugs.14 Although several
studies have reported QT prolongation in DR-
TB, the correlation of inflammatory markers
and QTc interval is still rarely being studied. In
this study, we aimed to evaluate the correlation
of moxifloxacin concentration, CRP, and
inflammatory cytokines with QTc interval in
DR-TB patients treated with shorter regimen.

METHODS
An observational analytic study with

consecutive sampling was conducted from
September 2019 to February 2020 in Dr.
Soetomo Hospital Surabaya, one of East
Indonesia TB referral hospitals. Study subjects
were RR pulmonary TB patients based on the
GeneXpert examinations with age 18 to 65 years
old who will start the intensive phase and who
are on the continuation phase of shorter treatment
regimens. RR-TB patients with baseline QTc
>500 ms, potassium <3.5 mmol/L, magnesium
<1.7 mmol/L, calcium <8.5 mmol/L, creatinine
clearance <30 cc/m, aspartate aminotransferase -
alanine aminotransferase (AST-ALT) >5x upper
limit normal (ULN), body mass index (BMI)
<18 kg/m2, on anti-arrhythmia therapy, anti-
depressant therapy, with bradycardia, anti-fungal
treatment (azoles), erythromycin therapy, and
phenytoin therapy were excluded from this study.

Vol 54 • Number 1 • January 2022 Correlation of Moxifloxacin Concentratin, C-Reactive Protein

The respondents were given an explanation
of the research and publications to be carried out.
All respondents information is kept confidential
and only used for research purposes. After getting
an explanation, the respondent is allowed to
refuse the study or resign in the middle of the
study. The respondents gave their written consent
and permission for publication of the letters and
to participate in the research. We confirm that
all the research meets the ethical guidelines and
in accordance with the Declaration of Helsinki.

Ethics
An informed consent was signed by all

participants and the ethics committee of
Dr. Soetomo Hospital with ethical clearance
number 1444/KEPK/VIII/2019 on August 23rd,
2019.

Operational Definition

Rifampicin-resistant tuberculosis (RR-TB)
was defined as the results of Mycobacterium
tuberculosis detected with rifampicin resistance
based on GeneXpert MTB/RIF.15 RR-TB patients
in intensive phase were defined as RR-TB
patients who are eligible for shorter regimens and
will start intensive phase of treatment. RR-TB
patients in continuation phase were defined as
RR-TB patients who have completed the intensive
phase (4-6 months), i.e. those who have sputum
smear conversion after the 4th, 5th, or 6th month.
Shorter regimens were as recommended by the
WHO in 2016 and the national program in 2019,
consisted of 4-6 Km – Mfx – Eto(Pro) – HHigh
Dose – Cfz – E – Z / 5 Mfx – Cfz – E – Z for
9-11 months.2,16 Electrocardiography (ECG)
was defined as a 12-lead surface heart recording
using an ECG machine. The QT interval is that
portion of the ECG that begins at the start of the
QRS complex and ends at the termination of
the T wave. The QTc referred to the corrected
QT interval using the Fredericia formula.14
The changes of QTc (ΔQTc) referred to the
difference between the QT interval at baseline and
the QT interval at 2 hours after taking the 48th-hour
dose, and 1 hour before taking the 72nd-hour dose.

Concentration of Moxifloxacin
Blood samples were collected and put into

heparin tubes at 2 hours after taking the 48th-hour

dose and 1 hour before taking the 72nd-hour dose.
Blood samples were centrifuged and the plasma
was stored in the deep freezer with a temperature
of -800 C. The moxifloxacin concentration was
measured by a validated method using High-
Performance Liquid Chromatography (HPLC).
The separation of moxifloxacin from the plasma
matrix using protein precipitation, followed by
measurements using the Waters HPLC Alliance
e2695 with a detector of Waters 2998 Photodiode
Array (PDA). 240 µL of acetonitrile solution
(100%) was added to the 200 µl of plasma
sample. The sample was then vortexed for 1
minute and centrifuged at a speed of 10,000 g for
5 minutes. A total of 200 µl of supernatant was
put into the vial and injected into the HPLC with
an injection volume of 10 µl. Separation using
a SunfireTM C18 column (4.6 x 100 mm, 5 µm;
Waters, Ireland). The mobile phase consisted
of 0.4% TEA in aquabides with a pH of ±3 and
100% of acetonitrile (75%:25% (v/v)). The flow
rate is 1 ml/min and the PDA detector was set at
a wavelength of 296 nm. Accuracy for standard
concentration curves is between 95.5% to
103.4%, depends on the standard concentration
level. The coefficient of variation for intra- and
inter-assay was less than 7.2% for the range from
0.204 to 10,200µg / mL. The lowest limit value
which can be quantified was 0.204 µg/mL.

Measurement of CRP Levels
Venous blood samples from each subject

were collected into heparin tubes. Serum was
separated by centrifugation at 3,000 rpm for 5
minutes and stored at 40 C for 24 hours for the
analysis.9 CRP levels were determined by an
immunoturbidimetric assay using SIEMENS
Dimension clinical chemistry system for
quantitative determination of CRP in serum and
plasma. This instrument automatically calculates
and prints the concentration of CRP in [mg/L]
mg/dL. Analytical measurement range was 0.5-
250.0 mg/L or 0.05-25.00 mg/dL.

Measurement of Inflammatory Cytokines
Levels

Samples of venous blood with an amount of
5 cc were taken from each patient and put into
EDTA serum tubes. All samples were stored in a
deep freezer with a temperature of -800 C. After

Tutik Kusmiati Acta Med Indones-Indones J Intern Med

the samples had sufficient amounts, all samples
were put at room temperature for 2 hours or at
40 C for a night. The samples were centrifuged
for 15 minutes to separate the blood plasma and
serum. The cytokines levels were measured using
the ELISA method with a kit of Elabsiences.

QTc Interval Measurement
QT interval was measured automatically

using ECG machine merc BLT E30 (Guangdong
Biolight Meditech, Germany, 2017) at baseline
before treatment, 2 hours after taking the 48th-
hour dose, and 1 hour before taking the 72nd-hour
dose. Heart rate-corrected QT (QTc) interval was
calculated using Fredericia formula,[14] manually
by cardiologists.

Data Analysis and Ethical Statement
The data obtained in this study were presented

as tables and graphics. Data were analyzed using
SPSS 21.0 software (IBM Corp., Armonk,
NY, USA). P-value <0.05 was considered
as significant statistically. This study was
conducted in accordance with the Declaration
of Helsinki. An informed consent was signed by
all participants. This study was approved by the
ethics committee of Dr. Soetomo Hospital with
ethical clearance number 1444/KEPK/VIII/2019
on August 23rd, 2019.

RESULTS
This study included 29 RR-TB patients

on intensive phase and 16 RR-TB patients on
continuation phase of shorter regimens. The
clinical symptoms found in this study were
cough, fever, chest pain, haemoptysis, weight
loss, night sweats, dyspnea at rest, and dyspnea
during activity. Table 1 showed that the clinical
symptoms of RR-TB patients improved in
continuation phase, but there is no significant
difference between the reported symptoms in
intensive phase and continuation phase. Albumin,
CRP, IL-1β, QTc baseline, and QTc at 2 hours
after the 48th dose showed significant differences
between RR-TB patients on intensive phase and
continuation phase with p = 0.002, <0.001, 0.040,
<0.001, and 0.026, respectively. While TNF-α,
IL-6, moxifloxacin concentration at 2 hours after
the 48th dose, moxifloxacin concentration and
QTc at 1 hour before 72nd dose between RR-TB

patients on intensive phase and continuation
phase showed no significant difference with p =
0.530, 0.477, 0.686, 0.610, and 0.325. This was
presented in Table 1.

Table 2 showed that CRP, TNF-α, IL-1β,
and IL-6 did not correlate with QTc interval in
intensive phase with p = 0.226, 0.281, 0.509,
and 0.886, respectively. CRP, TNF-α, IL-1β, and
IL-6 also did not correlate with QTc interval in
continuation phase with p = 0.805, 0.865, 0.406,
and 0.586, respectively. This result indicated that
inflammatory markers could not predict QTc
interval in our study.

At 2 hours after the 48th dose, it was known
that moxifloxacin concentration did not correlate
with QTc interval and ΔQTc, both in intensive
phase (p = 0.576 and 0.415) and continuation
phase (p = 0.691 and 0.353). At 1 hour before the
72nd- hour dose, moxifloxacin concentration also
did not correlate with QTc interval and ΔQTc in
intensive phase with p = 0.531 and 0.813, and
in continuation phase with p = 0.209 and 0.464,
as presented in Table 3.

Scatter plot in Figure 1 showed that the
distribution of CRP, TNF-α, IL-1β, and IL-6 did
not correlate with QTc interval. Levels of CRP,
TNF-α, IL-1β, and IL-6 are overlapping between
intensive and continuation phases, while QTc
interval showed an increased in continuation
phase.

T h e d i s t r i b u t i o n o f m o x i f l o x a c i n
concentration and QTc interval at 2 hours after
taking the 48th-hour dose and 1 hour before taking
the 72nd-hour dose did not form a specific pattern
as presented in Figure 2. This scatter plot showed
that moxifloxacin concentration did not correlate
with QTc interval, as the results of correlation
analysis in Table 3.

DISCUSSION
Multidrug-Resistant/Rifampicin-Resistant

TB (MDR/RR-TB) is an emerging threat to TB
control, with clinical presentation of patients with
MDR/RR-TB being identical to that of patients
with drug-susceptible disease.[17] All patients
with RR-TB in this study were symptomatic,
most commonly with cough (66.7% in intensive
phase and 33.3% in continuation phase),
other symptoms including fever, chest pain,

Vol 54 • Number 1 • January 2022 Correlation of Moxifloxacin Concentratin, C-Reactive Protein

Table 1. Characteristics of Study Subjects

Characteristics RR-TB on Start of Intensive Phase (N=29)
RR-TB on Start of

Continuation Phase (N=16) P-value

Age (years)* 37 (18-62) 44 (19-56) 0.569
Sex**

Women
Men

13 (59%)
16 (70%)

9 (41%)
7 (30%)

0.673

BMI (m/kg2)* 20.4 (18.03-28.65) 19.06 (18.26-27.68) 0.530
Diabetes mellitus** 14 (73.7%) 5 (26.3%) 0.429
Cough** 28 (66.7%) 14 (33.3%) 0.285
Fever** 12 (75%) 4 (25%) 0.272
Chest pain** 6 (100%) 0 (0%) 0.075
Haemoptysis** 9 (64.3%) 5 (35.7%) 1.000
Weight loss** 14 (60.9%) 9 (39.1%) 0.608
Night sweats** 10 (71.4%) 4 (28.6%) 0.738
Dyspnea at rest** 3 (60%) 2 (40%) 1.000
Dyspnea during activity** 7 (70%) 3 (30%) 1.000
Potassium (mmol/l)*** 4.3 ± 0.45 3.96 ± 0.4 0.019
Calcium mg/dl)*** 9.03 ±0.46 8.67 ± 0.2 0.001
Albumin*** 3.43 ± 0.28 3.65 ± 0.14 0.002
CRP (mg/dl)* 1.5 (0.2-10.9) 0.15 (0.1-0.6) <0.001
TNF-α (pg/mL)* 6.8 (0.13-36.22) 4.79 (0-43.34) 0.530
IL-1β (pg/mL)* 20.13 (2.23-708.7) 7.42 (0.6-113.47) 0.040
IL-6 (pg/mL)* 43.17 (10.14-1076) 40.61 (4.47-113.99) 0.477
QTc Baseline(ms)*** 417.28 ± 31.2 455.94 ± 16.6 <0.001
Moxifloxacin **
600
800

17 (60.8%)
12 (70.6%)

11 (39.2%)
5 (29.4%)

0.727

Moxy Conc (48+2) (µg/mL)*** 4.3 ± 2.32 4.61 ± 2.54 0.686
QTc 48+2 (ms)*** 444.38 ± 31.25 467.94 ± 35.7 0.026
∆QTc (48+2)-Baseline (ms)* 20 ((-17) – (81)) 2.5 ((-44) – (115)) 0.036
Moxy Conc (72-1) (µg/mL)* 1.01 (0.01 – 3.27) 0.91 (0.01 – 1.61) 0.610
QTc 72-1 (ms)* 448 (386-518) 447 (428-524) 0.325
∆QTc (48+2) - (72-1) (ms)* 0 ((-75) – (60)) 7.5 ((-77) – (52)) 0.122

* Median (min-max) using Mann-Whitney Test; ** Chi-square; ***Mean ± Standard Deviation using T-test; BMI = Body Mass
Index.

Table 2. Correlation Analysis at Baseline using Pearson or Spearman-rho Test

Intensive phase QTc baseline Continuation
phase

QTc baseline

R P R P
CRP (mg/dL) -0.232 0.226 CRP (mg/dL) 0.067 0.805
TNF-α (pg/mL) 0.207 0.281 TNF-α (pg/mL) 0.046 0.865
IL-1β (pg/mL) 0.128 0.509 IL-1β (pg/mL) -0.223 0.406
IL-6 (pg/mL) -0.028 0.886 IL-6 (pg/mL) -0.147 0.586

R: Correlation Coefficient; P: Sig. (2-tailed).

Table 3. Correlation Analysis at 2 Hours after the 48th Dose and at 1 Hour before the 72nd- Hour Dose

Moxi Conc at 48+2 Moxi Conc at 72-1
Intensive phase QTc at 48+2 R -0.108 QTc at 72-1 R 0.121

P 0.576 P 0.531
∆QTc ((48+2) –

Baseline))
R -0.157 ∆QTc ((48+2) –

(72-1))
R -0.046

P 0.415 P 0.813
Continuation
phase

QTc at 48+2 R 0.108 QTc at 72-1 R -0.332
P 0.691 P 0.209

∆QTc ((48+2) –
Baseline))

R 0.249 ∆QTc ((48+2) –
(72-1))

R -0.197
P 0.353 P 0.464

Correlation Analysis using Pearson or Spearman-rho Test; R: Correlation Coefficient; P: Sig. (2-tailed).

Tutik Kusmiati Acta Med Indones-Indones J Intern Med

haemoptysis, weight loss, night sweats, dyspnea
at rest, and dyspnea during activity. A study in
93 MDR-TB patients by Brode et al. (2015)
also reported productive cough as the most
common symptoms in MDR-TB, followed
by weight loss, malaise, fever, haemoptysis,
night sweats, and chest pain.18 The symptoms
were more often reported in intensive phase,
then improved in continuation phase (Table
1), as the intensive phase of RR-TB treatment
aimed to significantly decrease the bacillary
burden. The improved symptoms may results
from the decreased bacillary burden and the
decreased inflammation (inflammation caused
by Mycobacterium tuberculosis infection) after
intensive phase of treatment.

Interval QTc prolongation is a serious

effect and is often reported in DR-TB patients
treated with shorter regimens. Moxifloxacin is
considered as a QT-prolonging drug and is often
criticized to cause QTc prolongation in DR-TB
patients.1,6 Moreover, QT prolongation related
to inflammatory factors also has been widely
reported, as has been known that inflammation
occurs as a response to injury, lipid peroxidation,
and infection, including TB infection.26

In this study, RR-TB patients on intensive
phase of shorter regimen have a higher level of
CRP, TNF-α, IL-1β, and IL-6 levels, compared
to those in continuation phase. CRP and IL-1β,
and QTc baseline were significantly different
between RR-TB patients on intensive phase and
continuation phase with p-value of <0.001, 0.040,
and <0.001, respectively. While TNF-α and IL-6

Figure 1. Scatter Plot of Inflammatory Cytokines (TNF-α, IL-1β, and IL-6), C-Reactive Protein, and Baseline of QTc Interval
in RR-TB Patients.

Vol 54 • Number 1 • January 2022 Correlation of Moxifloxacin Concentratin, C-Reactive Protein

between RR-TB patients on intensive phase
and continuation phase showed no significant
difference with p = 0.530 and 0.477, respectively
(Table 1). A higher level of inflammatory
biomarkers in intensive phase showed that the
inflammation due to Mycobacterium tuberculosis
infection was still high because the patients have
just received DR-TB treatment, while patients on
continuation phase have been treated for a few
months and have experienced sputum conversion
which indicated decreased inflammation in
lung tissue. Pulmonary TB infection ellicits
an inflammatory process in lung tissue, which
is correlated with CRP levels changes,27 and
induction of inflammatory cytokines to regulate
immune system.25 This immune process depends
on Th1-cell activity, including TNF-α. IL-1β
directly kills Mycobacterium tuberculosis in
macrophages. IL-6 is a requirement in host
resistance to infection. IFN-γ , TNF-α , IL-12.28

At baseline examination, QTc interval
in continuation phase was found higher than
intensive phase (Table 1), while correlation
analysis in Table 2 showed that CRP, TNF-α,
IL-1β, and IL-6 did not correlate with QTc
interval in intensive phase and continuation
phase. This was different from previous studies
that reported a correlation between inflammation
marker and QTc prolongation. CRP levels
were found higher and correlated with QTc
prolongation in hypertensive and rheumatoid
arthritis patients.21-23 Other studies reported
increased TNF-α in elderly general population,
elevated IL-6 levels in patients who experienced
TdP, and higher levels of IL-1β in patients with
connective tissue diseases, all being risk factors
for long QTc intervals.

T h e c o r r e l a t i o n b e t w e e n C R P a n d
cardiovascular risk is through systemic
inflammation. Inflammatory cytokines such
as TNF-α, IL-6, and IL-1 act directly on
cardiomyocyte ion channels expression and
function, and may represent a risk factor for QTc
prolongation.7 Another study found that IL-6
negatively affected cardiomyocyte ion channel
function and increased risk for QT prolongation,
suggesting that patients with high levels of IL-6
should receive routine ECG and counseling if
other QTc prolonging risk factors are present.

Systemic inflammation promotes QTc-interval
prolongation via cytokine-mediated effects.
Released inflammatory cytokines are able to
directly affect the expression and/or function
of several cardiac ion channels, resulting in a
decrease of K+ current and/or an increase of
calcium current. While in this present study,
it was shown that inflammation due to DR-TB
infection did not correlate with QTc interval
(Table 2).

Another factor was considered for acquiring
QTc prolongation, and moxifloxacin as a
component in the standardized shorter regimen
was suspected to induce QTc prolongation. The
mechanism of drug-induced QT prolongation
is due to blockage of the human ether a-go-go
gene (hERG) that is responsible for the inward
potassium rectifier (IKr) repolarizing current.
[31-33] Our study showed that at 2 hours after the
48th dose, moxifloxacin concentration did not
correlate with QTc interval, both in intensive
and continuation phases. At 1 hour before the
72nd- hour dose, moxifloxacin also did not affect
QTc interval in intensive and continuation phases
(Table 3). Yoon et al. (2017) also revealed the
safe use of moxifloxacin on QTc changes in
DR-TB patients. Moxifloxacin at the dosage of
400, 600, or 800 mg does not correlate with the
QTc interval.

Moxifloxacin is relatively safe, and the
prolongation caused by moxifloxacin is
considered minimal or moderate, but should be
carefully monitored when other risk factors are
present. QT prolongation is usually asymptomatic
and requires routine ECG monitoring during QT
drug use, to ensure the safe use of moxifloxacin
and prevent serious adverse effects which can be
life-threatening.

CONCLUSION
O u r s t u d y f o u n d t h a t m o x i f l o x a c i n

concentration, CRP, and inflammatory cytokines
did not correlate with QTc interval in DR-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 DR-TB
patients received shorter regimens.

Tutik Kusmiati Acta Med Indones-Indones J Intern Med

ACKNOWLEDGMENTS
The authors would like to thank Mrs. Atika,

M.Sc., who helped us in statistical analysis.

CONFLICT OF INTERESTS
The authors report no conflicts of interest

in this work.

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