3 J Gandhara Nurs Alli Health Sci
ORIGINAL ARTICLE JGNAHS
:
:
January - June 2025
https://doi.org/10.37762/jgnahs.137
DIAGNOSTIC PERFORMANCE OF XPERT® MTB/XDR FOR DRUG-RESISTANT PULMONARY
TUBERCULOSIS
Muhammad Kashif Munir1, Faiz Ahmad Raza2, Muhammad Adnan3, Sana Rehman4, Ruqayya Khalid ,5
, Muhammad Saqib Saeed76
Asif Hanif
ABSTRACT
OBJECTIVES
The study aimed to determine the diagnostic accuracy of Xpert® MTB/XDR
assay for drug-resistant pulmonary tuberculosis by taking conventional drug
susceptibility testing (DST) as standard.
METHODOLOGY
In the cross-sectional analytical study, 1789 pulmonary TB suspects were
tested for Xpert® MTB/RIF assay from November 2022 to April 2023. Of
these 604 were Mycobacterium tuberculosis (MTB) positive and 57
rifampicin-resistant (RR). Two first -morning sputum specimens were
collected from all RR cases. One specimen was processed for Xpert®
MTB/XDR, and the other for Lowenstein Jensen (LJ) culture and
conventional DST.
RESULTS
Overall mean age was 36.6±16.6 years, and gender distribution was
comparable (49.1% vs. 50.9%). RR was 100.0% on Xpert® and 78.9% on
DST, MDR 77.2% on Xpert® and 66.7% on DST, pre-XDR 26.3% on Xpert®
and 31.6% on DST, and XDR 0.0% on Xpert ® and 5.3% on DST. Compared
to conventional DST, the accuracy of Xpert® was 79.0% for RR, 75.0% for
MDR, 81.0% for pre-XDR, and 95.0% for XDR-TB.
CONCLUSION
The Xpert® MTB/XDR assay demonstrated greater accuracy for drug-
resistant pulmonary tuberculosis, especially XDR-TB. However, more studies
are needed to validate the diagnostic performance of this new modality.
KEYWORDS: Drug Resistant, Tuberculosis, MDR, XDR, GeneXpert ®
How to cite this article
Munir MK, Raza FA, Adnan M,
Rehman S, Khalid R, Hanif A, etal.
Diagnostic Performance of Xpert®
MTB/XDR for Drug-Resistant
Pulmonary Tuberculosis. J Gandhara
Nurs Alli Health Sci. 2025;5(1): 3-8
Date of Submission:
Date Revised:
Date Acceptance:
1SRO, NIH-HRI TB Research Center,
King Edward Medical University,
Lahore
2PRO, NIH-HRI TB Research Center,
King Edward Medical University,
Lahore
4RO, Health Research Institute,
National Institute of Health, Islamabad
5Assistant Professor, Department of
Biochemistry, Kinnaird College for
Women, Lahore
6Assistant Professor, Department of
Pulmonology, King Edward Medical
University, Lahore
7Professor, Department of
Pulmonology, King Edward Medical
University, Lahore
Correspondence
3Muhammad Adnan, RO, Health
Research Institute, National Institute
of Health, Islamabad
+92-300-5494948
adnanpmrc@gmail.com
INTRODUCTION
beyond
The contagious nature of tuberculosis (TB) and its easy
transmission from person to person has set off a bunch
of micro-organisms known as Mycobacterium
tuberculosis complex (MTBC). On the other hand TB
infection deceits among the top ten causes of morbidity
and mortality through the single most communicable
disease.1 Characteristically MTBC infects the lungs in
humans to cause pulmonary TB however, micro-
organisms may approach every tissue in the body
the lungs to establish extra-pulmonary TB.2
Currents reports of the World Health Organization
(WHO) presented around eleven million patients who
had been infected with TB. An estimated rate of
incidence ranges from 114-140 patients 100 thousands
of the general population. Geologically, around 43%
global burden of TB is contained by Southeast East
Asia and Pakistan ranked the 5th highest TB-loaded
country around the globe stentorian 5.8% of the global
load.3 GeneXpert® MTB/RIF assay revolutionized not
only in early accurate diagnosis of TB but also
established the detection of drug resistance to
rifampicin. Drug-resistant (DR) TB along with
multidrug-resistant (MDR) TB poses a major risk to
Global Health. Drug-resistant TB has also been found
to be associated with various factors including non-
adherence and treatment default from patients, low-
quality drugs, low dosage of drugs, social stigma
among patients and various programmatic
deficiencies.4 Around 518000 new TB cases were
reported during 2019 in Pakistan comprising 15000
cases of Drug-resistant TB.5 Over the past couple of
decades, the emergence of DR-TB has presented an
even greater challenge, leading to confusion among
physicians and causing further distress for patients
30-10-2024
10-01-2025
12-01-2025
JGNAHS
4J Gandhara Nurs Alli Health SciJanuary - June 2025
affected by the disease. The options for treating DR-TB
cases are already limited, and the situation could
worsen if resistance develops against fluoroquinolones
and at least one of the three injectable drugs (amikacin,
capreomycin, or kanamycin), known as extensively
drug-resistant tuberculosis (XDR-TB).6
Implementation of End TB Strategy provides a right of
universal access to patients getting their drug
susceptibility testing (DST), which determines the
pathogen i.e. Mycobacterium tuberculosis (MTB)
being resistant or susceptible to specified anti-
tubercular drugs.3 After the success of GeneXpert®
MTB/RIF assay, another rapid Xpert® MTB/XDR test
also based on nucleic amplification detects TB along
drug susceptibility of various drugs other than
rifampicin in a single test cartridge. This test has been
recommended in all intermediate and peripheral
laboratories by the National TB Control Program. Like
MTB/RIF assay this test also detects MTB along
resistance to six drugs including isoniazid,
fluoroquinolones, ethionamide, amikacin,
capreomycin, and kanamycin simultaneously.7 Xpert®
MTB/XDR assay is based on real-time polymerase
chain reaction (PCR) which detects drug resistance
based on genetic mutations in various genes conferring
resistance to respective drugs. GeneXpert® MTB/RIF
assay proved to be very sensitive and accurate but
MTB/XDR assay is quite new and its accuracy may
vary in various regions due to differences in physical,
environmental and cultural characteristics. These
factors have been already proven to show their
influences on genetic characteristics and mutations.
Therefore it is necessary to observe its accuracy at the
local level for adoption and optimization results. Thus
present study aims to observe the accuracy of drug
susceptibility testing by Xpert® MTB/XDR assay.
METHODOLOGY
The cross-sectional analytical study was conducted at a
tertiary hospital from November 2022 to April 2023.
All patients tested rifampicin-resistant (RR) by Xpert®
MTB/RIF assay, aged 18 years and above, of either
gender were included. Samples from 1789 pulmonary
TB suspects were tested for Xpert® MTB/RIF assay, of
which 604 were found to have MTB and 57 were found
to have RR.A pre-designed proforma was used to
collect the demographic data, presence of any other
comorbidity and history of previous TB treatment.
Before taking an informed consent each patient was
explained about the purpose of the study. Patients
(n=57) were asked to provide two first-morning sputum
specimens. One sample was processed for Xpert®
MTB/XDR, while the other was processed for culture
and DST. Isolation of MTB was achieved by culture on
Lowenstein Jensen (LJ) media further drug proportion
method was used for DST. First-line drugs along their
final concentration in LJ media included in DST were
Isoniazid (0.2μg/ml), Rifampicin (40.0μg/ml),
Ethambutol (2.0μg/ml),8 Pyrazinamide (100.0μg/ml),9
and Streptomycin (4.0μg/ml). Second-line drugs were
Amikacin (4.0μg/ml), Kanamycin (5.0μg/ml),
Capreomycin (10.0μg/ml), Ofloxacin (2.0μg/ml),
Levofloxacin (1.0μg/ml), Moxifloxacin (0.5μg/ml),
Ethionamide (5.0μg/ml)8, Bedaquiline (1.0μg/ml),
Delamanid (1.0μg/ml),10 Clofazimine (1.0μg/ml), and
Linezolid (1.0μg/ml).11 MDR-TB is defined as
resistance to at least isoniazid and rifampicin, and
XDR-TB is defined as MDR-TB with additional
resistance to any fluoroquinolone, and to at least one
injectable second-line drug.12 Data was entered and
analyzed using Statistical Package for Social Sciences
(SPSS) version 26.0. Categorical data was presented in
frequency and percentages, while continuous data was
presented in mean and standard deviation. Comparative
data of DST for Xpert® MTB/XDR and conventional
drug proportion phenotypic susceptibility were
presented in frequency and percentages of new drug-
resistant TB patients and Cat I treated patients. The chi-
square test was also applied and p-value ≤0.05 was
considered significant. Cross tabulation was used to
calculate the sensitivity, specificity, positive predictive
value (PPV), negative predictive value (NPV) and
accuracy using MedCalc online software.
RESULTS
The overall mean age of respondents was 36.6±16.6
years with a higher mean age of males than females
(42.9±17.3 vs. 30.5±13.7 years, p 0.004).
Diagnostic Performance of Xpert® MTB/XDR for Drug
4J Gandhara Nurs Alli Health SciJanuary - June 2025
affected by the disease. The options for treating DR-TB
cases are already limited, and the situation could
worsen if resistance develops against fluoroquinolones
and at least one of the three injectable drugs (amikacin,
capreomycin, or kanamycin), known as extensively
drug-resistant tuberculosis (XDR-TB).6
Implementation of End TB Strategy provides a right of
universal access to patients getting their drug
susceptibility testing (DST), which determines the
pathogen i.e. Mycobacterium tuberculosis (MTB)
being resistant or susceptible to specified anti-
tubercular drugs.3 After the success of GeneXpert®
MTB/RIF assay, another rapid Xpert® MTB/XDR test
also based on nucleic amplification detects TB along
drug susceptibility of various drugs other than
rifampicin in a single test cartridge. This test has been
recommended in all intermediate and peripheral
laboratories by the National TB Control Program. Like
MTB/RIF assay this test also detects MTB along
resistance to six drugs including isoniazid,
fluoroquinolones, ethionamide, amikacin,
capreomycin, and kanamycin simultaneously.7 Xpert®
MTB/XDR assay is based on real-time polymerase
chain reaction (PCR) which detects drug resistance
based on genetic mutations in various genes conferring
resistance to respective drugs. GeneXpert® MTB/RIF
assay proved to be very sensitive and accurate but
MTB/XDR assay is quite new and its accuracy may
vary in various regions due to differences in physical,
environmental and cultural characteristics. These
factors have been already proven to show their
influences on genetic characteristics and mutations.
Therefore it is necessary to observe its accuracy at the
local level for adoption and optimization results. Thus
present study aims to observe the accuracy of drug
susceptibility testing by Xpert® MTB/XDR assay.
METHODOLOGY
The cross-sectional analytical study was conducted at a
tertiary hospital from November 2022 to April 2023.
All patients tested rifampicin-resistant (RR) by Xpert®
MTB/RIF assay, aged 18 years and above, of either
gender were included. Samples from 1789 pulmonary
TB suspects were tested for Xpert® MTB/RIF assay, of
which 604 were found to have MTB and 57 were found
to have RR.A pre-designed proforma was used to
collect the demographic data, presence of any other
comorbidity and history of previous TB treatment.
Before taking an informed consent each patient was
explained about the purpose of the study. Patients
(n=57) were asked to provide two first-morning sputum
specimens. One sample was processed for Xpert®
MTB/XDR, while the other was processed for culture
and DST. Isolation of MTB was achieved by culture on
Lowenstein Jensen (LJ) media further drug proportion
method was used for DST. First-line drugs along their
final concentration in LJ media included in DST were
Isoniazid (0.2μg/ml), Rifampicin (40.0μg/ml),
Ethambutol (2.0μg/ml),8 Pyrazinamide (100.0μg/ml),9
and Streptomycin (4.0μg/ml). Second-line drugs were
Amikacin (4.0μg/ml), Kanamycin (5.0μg/ml),
Capreomycin (10.0μg/ml), Ofloxacin (2.0μg/ml),
Levofloxacin (1.0μg/ml), Moxifloxacin (0.5μg/ml),
Ethionamide (5.0μg/ml)8, Bedaquiline (1.0μg/ml),
Delamanid (1.0μg/ml),10 Clofazimine (1.0μg/ml), and
Linezolid (1.0μg/ml).11 MDR-TB is defined as
resistance to at least isoniazid and rifampicin, and
XDR-TB is defined as MDR-TB with additional
resistance to any fluoroquinolone, and to at least one
injectable second-line drug.12 Data was entered and
analyzed using Statistical Package for Social Sciences
(SPSS) version 26.0. Categorical data was presented in
frequency and percentages, while continuous data was
presented in mean and standard deviation. Comparative
data of DST for Xpert® MTB/XDR and conventional
drug proportion phenotypic susceptibility were
presented in frequency and percentages of new drug-
resistant TB patients and Cat I treated patients. The chi-
square test was also applied and p-value ≤0.05 was
considered significant. Cross tabulation was used to
calculate the sensitivity, specificity, positive predictive
value (PPV), negative predictive value (NPV) and
accuracy using MedCalc online software.
RESULTS
The overall mean age of respondents was 36.6±16.6
years with a higher mean age of males than females
(42.9±17.3 vs. 30.5±13.7 years, p 0.004).
Diagnostic Performance of Xpert® MTB/XDR for Drug
5 J Gandhara Nurs Alli Health Sci
JGNAHS
January - June 2025
n %
Age (years)
< 25 22 38.6%
25-44 14 24.6%
45-64 17 29.8%
≥ 65 04 7.0%
Gender Male 28 49.1%
Female 29 50.9%
District
Lahore 46 80.7%
Gujranwala 03 5.3%
Sheikhupura 04 7.0%
Other 04 7.0%
Addiction
None 50 87.7%
Smoking 06 10.5%
Other 01 1.8%
Comorbidity
None 42 73.7%
Diabetes mellitus 13 22.8%
Heart disease 01 1.8%
Diabetes & Heart
disease 01 1.8%
History of previous
treatment
New 29 50.9%
Cat I 28 49.1%
History of second-
line treatment
Yes 03 5.3%
No 54 94.7%
Treatment Regimen
group
New 29 50.9%
Others previous
treated 25 43.9%
Failure 01 1.8%
Relapse 01 1.8%
Transfer In 01 1.8%
Table 1: Demographic Characteristics of the Study Population
The accuracy rate of Xpert® rifampicin-resistance with
conventional DST has remained to be 79.0% with a
sensitivity of 100.0%. However, specificity and NPV
could not be calculated due to the absence of
rifampicin negative on Xpert®. Isoniazid also
presented an accuracy of 84.2% with Xpert®.
Sensitivity, specificity, PPV, NPV and accuracy of all
drugs tested through Xpert® MTB/XDR are presented
in Table 2.
Table 2: Mono drug resistance by Xpert® compared to
conventional DST
Drug Sensitiviy
%
Specif
icity %
PPV % NPV % Accura
cy %
Isoniazid 90.7 64.3 88.6 69.2 84.2
Rifampicin 100.0 - 78.9 - 78.9
Ethionamide - 98.3 0 100.0 -
Ofloxacin - 71.9 0 100.0 -
Levofloxacin 65.2 97.1 93.8 80.5 84.2
Moxifloxacin 80.0 76.9 25.0 97.6 77.2
Amikacin 0.0 100.0 - 94.7 94.7
Kanamycin - 100.0 - 100.0 -
Capreomycin - 100.0 - 100.0 -
RR was 100.0% on Xpert® and 78.9% on DST, MDR
77.2% on Xpert® and 66.7% on DST, pre-XDR 26.3%
on Xpert® and 31.6% on DST, and XDR 0.0% on
Xpert® and 5.3% on DST. Compared to conventional
DST, the accuracy of Xpert® was 79.0% for RR, 75.0%
for MDR, 81.0% for pre-XDR, and 95.0% for XDR-
TB as shown in Table 3.
Table 3: Poly drug resistance by Xpert® compared to
conventional DST
RR: Rifampicin-resistant, MDR: Multidrug-resistant,
Pre-XDR: Pre-extensively drug-resistant, XDR:
Extensively drug-resistant, DST: Drug susceptibility
testing, PPV: Positive predictive value, NPV: Negative
predictive value.
All patients presenting RR conferred mutations in the
rpoB gene through GeneXpert®. The Xpert®
MTB/XDR assay conferred resistance in 77.2% of the
RR cases. Fluoroquinolone resistance was found in
28.1% of cases and no resistance was found in
injectable drugs i.e. Amikacin, kanamycin and
capreomycin as presented in Table 4. Chi-square test
was applied and an insignificant difference (p -value
>0.05) was found in new and Cat I treated cases.
Conventi
onal DST
Sensi
tivity
%
Speci
ficity
%
PPV
%
NPV
%
Accur
acy %
Yes No
Xpe
rt
RR Yes 45 12 100.0 0.0 78.9 0.0 78.9
No 0 0
MDR Yes 34 10 89.0 47.0 77.0 69.0 75.0
No 04 09
Pre-
XDR
Yes 11 04 61.0 90.0 73.0 83.0 81.0
No 07 35
Yes 0 0 0.0 100.0 0.0 95.0 95.0
No 03 54
XDR
Table 4: Drug susceptibility in New and Cat1 Treated TB cases
Xpert® Susceptibility Previous History of
Treatment
Total
New Cat I
n % n % n %
Isoniazid Resistant 23 79.3 21 75.0 44 77.2
Sensitive 06 20.7 07 25.0 13 22.8
Ethionam
ide
Resistant 01 3.4 0 0.0 01 1.8
Sensitive 28 96.6 28 100.0 56 98.2
Fluoroqui
nolones
Resistant 07 24.1 09 32.1 16 28.1
Sensitive 22 75.9 19 67.9 41 71.9
Amikacin,
Kanamycin
& Capreom
ycin
Resistant 0 0.0 0 0.0 0 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Conventional DST of first- and second-line drugs are
presented in Table 5. Chi-square test was applied and
only rifampicin showed a significant difference (p -
value <0.05) of susceptibility in new and previously
treated cases with Cat I, while all other drugs showed
insignificant differences (p-values >0.05). For
fluoroquinolones resistance, a significant difference
was found for levofloxacin (p-value = 0.001) and
moxifloxacin (p-value = 0.019).
Diagnostic Performance of Xpert® MTB/XDR for Drug
JGNAHS
January - June 2025
n %
Age (years)
< 25 22 38.6%
25-44 14 24.6%
45-64 17 29.8%
≥ 65 04 7.0%
Gender Male 28 49.1%
Female 29 50.9%
District
Lahore 46 80.7%
Gujranwala 03 5.3%
Sheikhupura 04 7.0%
Other 04 7.0%
Addiction
None 50 87.7%
Smoking 06 10.5%
Other 01 1.8%
Comorbidity
None 42 73.7%
Diabetes mellitus 13 22.8%
Heart disease 01 1.8%
Diabetes & Heart
disease 01 1.8%
History of previous
treatment
New 29 50.9%
Cat I 28 49.1%
History of second-
line treatment
Yes 03 5.3%
No 54 94.7%
Treatment Regimen
group
New 29 50.9%
Others previous
treated 25 43.9%
Failure 01 1.8%
Relapse 01 1.8%
Transfer In 01 1.8%
Table 1: Demographic Characteristics of the Study Population
The accuracy rate of Xpert® rifampicin-resistance with
conventional DST has remained to be 79.0% with a
sensitivity of 100.0%. However, specificity and NPV
could not be calculated due to the absence of
rifampicin negative on Xpert®. Isoniazid also
presented an accuracy of 84.2% with Xpert®.
Sensitivity, specificity, PPV, NPV and accuracy of all
drugs tested through Xpert® MTB/XDR are presented
in Table 2.
Table 2: Mono drug resistance by Xpert® compared to
conventional DST
Drug Sensitiviy
%
Specif
icity %
PPV % NPV % Accura
cy %
Isoniazid 90.7 64.3 88.6 69.2 84.2
Rifampicin 100.0 - 78.9 - 78.9
Ethionamide - 98.3 0 100.0 -
Ofloxacin - 71.9 0 100.0 -
Levofloxacin 65.2 97.1 93.8 80.5 84.2
Moxifloxacin 80.0 76.9 25.0 97.6 77.2
Amikacin 0.0 100.0 - 94.7 94.7
Kanamycin - 100.0 - 100.0 -
Capreomycin - 100.0 - 100.0 -
RR was 100.0% on Xpert® and 78.9% on DST, MDR
77.2% on Xpert® and 66.7% on DST, pre-XDR 26.3%
on Xpert® and 31.6% on DST, and XDR 0.0% on
Xpert® and 5.3% on DST. Compared to conventional
DST, the accuracy of Xpert® was 79.0% for RR, 75.0%
for MDR, 81.0% for pre-XDR, and 95.0% for XDR-
TB as shown in Table 3.
Table 3: Poly drug resistance by Xpert® compared to
conventional DST
RR: Rifampicin-resistant, MDR: Multidrug-resistant,
Pre-XDR: Pre-extensively drug-resistant, XDR:
Extensively drug-resistant, DST: Drug susceptibility
testing, PPV: Positive predictive value, NPV: Negative
predictive value.
All patients presenting RR conferred mutations in the
rpoB gene through GeneXpert®. The Xpert®
MTB/XDR assay conferred resistance in 77.2% of the
RR cases. Fluoroquinolone resistance was found in
28.1% of cases and no resistance was found in
injectable drugs i.e. Amikacin, kanamycin and
capreomycin as presented in Table 4. Chi-square test
was applied and an insignificant difference (p -value
>0.05) was found in new and Cat I treated cases.
Conventi
onal DST
Sensi
tivity
%
Speci
ficity
%
PPV
%
NPV
%
Accur
acy %
Yes No
Xpe
rt
RR Yes 45 12 100.0 0.0 78.9 0.0 78.9
No 0 0
MDR Yes 34 10 89.0 47.0 77.0 69.0 75.0
No 04 09
Pre-
XDR
Yes 11 04 61.0 90.0 73.0 83.0 81.0
No 07 35
Yes 0 0 0.0 100.0 0.0 95.0 95.0
No 03 54
XDR
Table 4: Drug susceptibility in New and Cat1 Treated TB cases
Xpert® Susceptibility Previous History of
Treatment
Total
New Cat I
n % n % n %
Isoniazid Resistant 23 79.3 21 75.0 44 77.2
Sensitive 06 20.7 07 25.0 13 22.8
Ethionam
ide
Resistant 01 3.4 0 0.0 01 1.8
Sensitive 28 96.6 28 100.0 56 98.2
Fluoroqui
nolones
Resistant 07 24.1 09 32.1 16 28.1
Sensitive 22 75.9 19 67.9 41 71.9
Amikacin,
Kanamycin
& Capreom
ycin
Resistant 0 0.0 0 0.0 0 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Conventional DST of first- and second-line drugs are
presented in Table 5. Chi-square test was applied and
only rifampicin showed a significant difference (p -
value <0.05) of susceptibility in new and previously
treated cases with Cat I, while all other drugs showed
insignificant differences (p-values >0.05). For
fluoroquinolones resistance, a significant difference
was found for levofloxacin (p-value = 0.001) and
moxifloxacin (p-value = 0.019).
Diagnostic Performance of Xpert® MTB/XDR for Drug
6J Gandhara Nurs Alli Health Sci
JGNAHS
January - June 2025
Previous History of
Treatment Total
New Cat I
n % n % n %
Rifampicin Resistant 19 65.5 26 92.9 45 78.9
Sensitive 10 34.5 02 7.1 12 21.1
Isoniazid Resistant 20 69.0 23 82.1 43 75.4
Sensitive 09 31.0 05 17.9 14 24.6
Ethambutol Resistant 02 6.9 00 0.0 02 3.5
Sensitive 27 93.1 28 100.0 55 96.5
Pyrazinamide Resistant 08 27.6 03 10.7 11 19.3
Sensitive 21 72.4 25 89.3 46 80.7
Streptomycin Resistant 07 24.1 08 28.6 15 26.3
Sensitive 22 75.9 20 71.4 42 73.7
Kanamycin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Amikacin Resistant 0 0.0 03 10.7 03 5.3
Sensitive 29 100.0 25 89.3 54 94.7
Capreomycin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Ofloxacin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Levofloxacin Resistant 09 31.0 14 50.0 23 40.4
Sensitive 20 69.0 14 50.0 34 59.6
Moxifloxacin Resistant 01 3.4 04 14.3 05 8.8
Sensitive 28 96.6 24 85.7 52 91.2
Ethionamide Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Clofazimine Resistant 01 3.4 02 7.1 03 5.3
Sensitive 28 96.6 26 92.9 54 94.7
Bedaquiline Resistant 01 3.4 03 10.7 04 7.0
Sensitive 28 96.6 25 89.3 53 93.0
Delamanid Resistant 01 3.4 01 3.6 02 3.5
Sensitive 28 96.6 27 96.4 55 96.5
Linezolid Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Table 5: Comparison of conventional susceptibility among new
and Cat I TB cases
DISCUSSION
With the advancement in technology, man has sought
after many valuable and safer technologies in the field
of medical technology. The invention of the PCR
technique by Kary Mullis in 1985 opened new horizons
in many fields of current science including medical
diagnostics. The infectious nature of various
microorganisms like MTBC are great biohazard for the
safety of lab personnel as the disease spreads through
airborne aerosols. The great advent of Xpert® over
conventional PCR is that the former uses single-step
closed cassettes consisting of various chambers for
DNA extraction, amplification and detection which
was a great breakthrough in the diagnosis of TB as well
as rifampicin resistance in just two hours. The
sensitivity of Xpert® MTB RIF was further enhanced
by introducing the second generation in the name
Xpert® MTB Ultra.13 A lot of literature on the accuracy
of GeneXpert® diagnosis of MTB is present but the
focus on comparing the conventional DST is
negligible. The accuracy of rifampicin resistance (RR)
in the present study remained at 78.95% when plotted
against the gold standard drug proportion method on LJ
media. Sensitivity in this case remained to be 100%
whereas specificity could not be calculated due to the
absence of rifampicin-sensitive cases on GeneXpert®.
Results accuracy are though in agreement with studies
presenting sensitivity of this test in the range of 61.8%
to 85% among pulmonary TB patients.14,15 Interestingly
all of the sensitivity, specificity, PPV, NPV and
accuracy were calculated for only Isoniazid,
Levofloxacin and moxifloxacin due to the presence of
all categories required in 2x2 table in this study. More
amusingly conventional DST presented 23(40.4%)
cases of levofloxacin resistance, 5(8.8%) moxifloxacin
and none of the cases resistant to Ofloxacin. All of
these three drugs belong to the same class of
fluoroquinolones. Genetically gyrA and gyrB are
reported to be associated with susceptibility of
fluoroquinolones. Only 16(28.1%) cases were found to
be resistant to Xpert®. Quinolone resistance
determining region (QRDR) includes 87-95 (261-285
nucleotides) codon region for gyrA and codon 531-544
or 492-505 (1596-1632 nucleotides) for gyrB are used
in Xpert® MTB/XDR.16 Even significant differences
(p-value <0.05) are reported for levofloxacin and
moxifloxacin but no resistance to Ofloxacin also
questioned the credibility of Xpert® MTB/XDR being
used for all quinolone. Ofloxacin is a second-
generation quinolone while levofloxacin and
moxifloxacin belong to the third generation of
quinolones. A study has presented cross-resistance
among Ofloxacin, moxifloxacin and levofloxacin by
finding mutations in the QRDR of gyrA. These
mutations have also been found to have a positive
correlation with higher minimum inhibitory
concentrations on LJ media.17 Debate among these
three quinolones in the treatment of drug-resistant TB
continuous on early bacterial activity, dosage, safety
profile and side effects like higher QT interval in
echocardiograph.18 Unlike other fluoroquinolones
chemical structure of Ofloxacin contains an oxazine
ring which links the nitrogen at the 1st position and
carbon at the 8th position of the quinolone ring thus
reported to suppress the drug metabolism in-vivo.19
Moxifloxacin bears a cyclopropyl substituent at the 1st
position and methoxy substituent at the 8th position
with two more differences than Ofloxacin. 20
Levofloxacin is a chiral fluorinated carboxy-quinolone
which is an enantiomer of Ofloxacin.21 Only three
(5.3%) cases were resistant to amikacin in phenotypic
DST whereas Xpert® MTB/XDR showed no mutation
in the rrs gene at present. Domenech et al, have
claimed a rare mutation in the rrs gene of MTB among
Diagnostic Performance of Xpert® MTB/XDR for Drug
JGNAHS
January - June 2025
Previous History of
Treatment Total
New Cat I
n % n % n %
Rifampicin Resistant 19 65.5 26 92.9 45 78.9
Sensitive 10 34.5 02 7.1 12 21.1
Isoniazid Resistant 20 69.0 23 82.1 43 75.4
Sensitive 09 31.0 05 17.9 14 24.6
Ethambutol Resistant 02 6.9 00 0.0 02 3.5
Sensitive 27 93.1 28 100.0 55 96.5
Pyrazinamide Resistant 08 27.6 03 10.7 11 19.3
Sensitive 21 72.4 25 89.3 46 80.7
Streptomycin Resistant 07 24.1 08 28.6 15 26.3
Sensitive 22 75.9 20 71.4 42 73.7
Kanamycin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Amikacin Resistant 0 0.0 03 10.7 03 5.3
Sensitive 29 100.0 25 89.3 54 94.7
Capreomycin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Ofloxacin Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Levofloxacin Resistant 09 31.0 14 50.0 23 40.4
Sensitive 20 69.0 14 50.0 34 59.6
Moxifloxacin Resistant 01 3.4 04 14.3 05 8.8
Sensitive 28 96.6 24 85.7 52 91.2
Ethionamide Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Clofazimine Resistant 01 3.4 02 7.1 03 5.3
Sensitive 28 96.6 26 92.9 54 94.7
Bedaquiline Resistant 01 3.4 03 10.7 04 7.0
Sensitive 28 96.6 25 89.3 53 93.0
Delamanid Resistant 01 3.4 01 3.6 02 3.5
Sensitive 28 96.6 27 96.4 55 96.5
Linezolid Resistant 00 0.0 00 0.0 00 0.0
Sensitive 29 100.0 28 100.0 57 100.0
Table 5: Comparison of conventional susceptibility among new
and Cat I TB cases
DISCUSSION
With the advancement in technology, man has sought
after many valuable and safer technologies in the field
of medical technology. The invention of the PCR
technique by Kary Mullis in 1985 opened new horizons
in many fields of current science including medical
diagnostics. The infectious nature of various
microorganisms like MTBC are great biohazard for the
safety of lab personnel as the disease spreads through
airborne aerosols. The great advent of Xpert® over
conventional PCR is that the former uses single-step
closed cassettes consisting of various chambers for
DNA extraction, amplification and detection which
was a great breakthrough in the diagnosis of TB as well
as rifampicin resistance in just two hours. The
sensitivity of Xpert® MTB RIF was further enhanced
by introducing the second generation in the name
Xpert® MTB Ultra.13 A lot of literature on the accuracy
of GeneXpert® diagnosis of MTB is present but the
focus on comparing the conventional DST is
negligible. The accuracy of rifampicin resistance (RR)
in the present study remained at 78.95% when plotted
against the gold standard drug proportion method on LJ
media. Sensitivity in this case remained to be 100%
whereas specificity could not be calculated due to the
absence of rifampicin-sensitive cases on GeneXpert®.
Results accuracy are though in agreement with studies
presenting sensitivity of this test in the range of 61.8%
to 85% among pulmonary TB patients.14,15 Interestingly
all of the sensitivity, specificity, PPV, NPV and
accuracy were calculated for only Isoniazid,
Levofloxacin and moxifloxacin due to the presence of
all categories required in 2x2 table in this study. More
amusingly conventional DST presented 23(40.4%)
cases of levofloxacin resistance, 5(8.8%) moxifloxacin
and none of the cases resistant to Ofloxacin. All of
these three drugs belong to the same class of
fluoroquinolones. Genetically gyrA and gyrB are
reported to be associated with susceptibility of
fluoroquinolones. Only 16(28.1%) cases were found to
be resistant to Xpert®. Quinolone resistance
determining region (QRDR) includes 87-95 (261-285
nucleotides) codon region for gyrA and codon 531-544
or 492-505 (1596-1632 nucleotides) for gyrB are used
in Xpert® MTB/XDR.16 Even significant differences
(p-value <0.05) are reported for levofloxacin and
moxifloxacin but no resistance to Ofloxacin also
questioned the credibility of Xpert® MTB/XDR being
used for all quinolone. Ofloxacin is a second-
generation quinolone while levofloxacin and
moxifloxacin belong to the third generation of
quinolones. A study has presented cross-resistance
among Ofloxacin, moxifloxacin and levofloxacin by
finding mutations in the QRDR of gyrA. These
mutations have also been found to have a positive
correlation with higher minimum inhibitory
concentrations on LJ media.17 Debate among these
three quinolones in the treatment of drug-resistant TB
continuous on early bacterial activity, dosage, safety
profile and side effects like higher QT interval in
echocardiograph.18 Unlike other fluoroquinolones
chemical structure of Ofloxacin contains an oxazine
ring which links the nitrogen at the 1st position and
carbon at the 8th position of the quinolone ring thus
reported to suppress the drug metabolism in-vivo.19
Moxifloxacin bears a cyclopropyl substituent at the 1st
position and methoxy substituent at the 8th position
with two more differences than Ofloxacin. 20
Levofloxacin is a chiral fluorinated carboxy-quinolone
which is an enantiomer of Ofloxacin.21 Only three
(5.3%) cases were resistant to amikacin in phenotypic
DST whereas Xpert® MTB/XDR showed no mutation
in the rrs gene at present. Domenech et al, have
claimed a rare mutation in the rrs gene of MTB among
Diagnostic Performance of Xpert® MTB/XDR for Drug
7 J Gandhara Nurs Alli Health Sci
JGNAHS
January - June 2025
DR isolates, further exact antibiotic resistance among
aminoglycosides conferring mutation in this specific
gene was also not reached previously. Additionally,
this gene does not converse cross-resistance among
other injectables i.e. capreomycin and kanamycin. A
substantial in vitro mutation fitness defect has also
been claimed to hurdle in its appearance thus making it
rare.22 Mutations in eis promoter have also been
debatable while a recent study has also claimed a novel
mutation in the rrs gene in kanamycin, capreomycin
and amikacin which are not comparable in this study as
none of the cases conferred resistance by Xpert®
MTB/XDR assay and all cases remained sensitive to
kanamycin and capreomycin phenotypically. Isoniazid
susceptibility presented good agreement rates of 75.4%
and 77.2% among GeneXpert® RR cases
phenotypically and genetically on Xpert® respectively.
Conclusively only 78.9% of RR cases by GeneXpert®
showed phenotypic resistance to rifampicin. Isoniazid
also showed a good agreement rate and sufficient gene
targets are included in the assay. Mutations in gyrA and
gyrB do not generalize the resistance among all
fluoroquinolones due to many differences in chemical
structures, absorbance and serum bioavailability of
drugs. Although Xpert® MDR-TB is a great addition to
prompt diagnosis of complex DR-TB cases more work
is needed to address the issues in finding genotypic
drug resistance for quinolones and all injectable drugs
for TB.
LIMITATIONS
The limitations of the study include observational study
design, purposive enrollment of patients and small
sample size.
CONCLUSIONS
The Xpert® MTB/XDR assay demonstrated greater
accuracy for drug-resistant pulmonary tuberculosis,
especially XDR-TB. However, more studies are needed
to validate the diagnostic performance of this new
modality.
CONFLICT OF INTEREST: None
FUNDING SOURCES: None
REFERENCES
1. World Health Organization (WHO). Global tuberculosis report
2020. 2020 [updated 2021, cited 2024]. Available from:
https://www.who.int/publications/i/item/9789240013131
2. Rehman S, Munir MK, Iqbal R, Saeed S. Pattern, diagnosis and
treatment outcome of extra pulmonary tuberculosis. Pak J Chest
Med. 2018;24(3):147-51.
3. World Health Organization (WHO). Global tuberculosis report
2021. 2021 [updated 2022, cited 2024]. Available from:
https://www.who.int/publications/i/item/9789240037021
4. Iqbal R, Munir MK, Rehman S, Saeed S. Drug resistant
tuberculosis: Pattern seen among patients visiting mayo
hospital, lahore. Pak J Med Res. 2018;57(4):132-7.
5. World Health Organization (WHO). Global tuberculosis report
2019. 2019 [cited 2024]. Available from:
http://www.who.int/tb/publications/global_report/en/
6. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T,
Lalloo U, et al. Extensively drug-resistant tuberculosis as a
cause of death in patients co-infected with tuberculosis and hiv
in a rural area of south africa. Lancet. 2006;368(9547):1575-80.
7. Pillay S, Steingart KR, Davies GR, Chaplin M, De Vos M,
Schumacher SG, et al. Xpert MTB/XDR for detection of
pulmonary tuberculosis and resistance to isoniazid,
fluoroquinolones, ethionamide, and amikacin. Cochrane
Database Syst Rev. 2022;5(5):CD014841. doi:
10.1002/14651858.CD014841.pub2.
8. Association of Public Health Laboratories (APHL). Drug
susceptibility testing for M. tuberculosis complex [Internet].
2020 [cited 2024]. Available from:
https://www.aphl.org/programs/infectious_disease/tuberculosis/
TBCore/DSTslides_updated_FINAL.pdf
9. Iqbal R, Tabbassum M, Shabbir I, Munir K, Khan S, Khan M.
Multi drug resistance tuberculosis: Pattern seen in last 13 years.
Pak J Med Res. 2011;50(1):10-4.
10. Yang JS, Kim KJ, Choi H, Lee SH. Delamanid, bedaquiline,
and linezolid minimum inhibitory concentration distributions
and resistance-related gene mutations in multidrug-resistant and
extensively drug-resistant tuberculosis in Korea. Ann Lab Med.
2018;38(6):563-8. Erratum in: Ann Lab Med. 2019;39(1):113.
doi: 10.3343/alm.2019.39.1.113.
11. Singh K, Sharma S, Banerjee T, Gupta A, Anupurba S.
Mutation detection and minimum inhibitory concentration
determination against linezolid and clofazimine in confirmed
XDR-TB clinical isolates. BMC Microbiol. 2022;22(1):236.
doi: 10.1186/s12866-022-02622-x.
12. World Health Organization. WHO announces updated
definitions of extensively drug-resistant tuberculosis [Internet].
www.who.int. 2021. Available from:
https://www.who.int/news/item/27-01-2021-who-announces-
updated-definitions-of-extensively-drug-resistant-tuberculosis
13. Li Z. The value of GeneXpert MTB/RIF for detection in
tuberculosis: A bibliometrics-based analysis and review. J Anal
Methods Chem. 2022;2022:2915018. doi:
10.1155/2022/2915018.
14. Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N,
Schumacher SG, et al. Xpert ultra versus xpert mtb/rif for
pulmonary tuberculosis and rifampicin resistance in adults with
presumptive pulmonary tuberculosis. Cochrane Database Syst
Rev. 2021(2):CD009593.
15. Shapiro AE, Ross JM, Yao M, Schiller I, Kohli M, Dendukuri
N, et al. Xpert mtb/rif and xpert ultra assays for screening for
pulmonary tuberculosis and rifampicin resistance in adults,
irrespective of signs or symptoms. Cochrane Database Syst
Rev. 2021(3):CD013694.
2015;59(9):5427
16. Cephide. Xpert MTB-XDR ENGLISH Package Insert 302-
3514 Rev C [Internet]. 2021 [cited 2024. Available from: Xpert
MTB-XDR ENGLISH Package Insert 302-3514 Rev C.fm
17. Willby M, Sikes RD, Malik S, Metchock B, Posey JE.
Correlation between gyra substitutions and ofloxacin,
levofloxacin, and moxifloxacin cross-resistance in
mycobacterium tuberculosis. Antimicrob Agents Chemother.
-34.
Diagnostic Performance of Xpert® MTB/XDR for Drug
JGNAHS
January - June 2025
DR isolates, further exact antibiotic resistance among
aminoglycosides conferring mutation in this specific
gene was also not reached previously. Additionally,
this gene does not converse cross-resistance among
other injectables i.e. capreomycin and kanamycin. A
substantial in vitro mutation fitness defect has also
been claimed to hurdle in its appearance thus making it
rare.22 Mutations in eis promoter have also been
debatable while a recent study has also claimed a novel
mutation in the rrs gene in kanamycin, capreomycin
and amikacin which are not comparable in this study as
none of the cases conferred resistance by Xpert®
MTB/XDR assay and all cases remained sensitive to
kanamycin and capreomycin phenotypically. Isoniazid
susceptibility presented good agreement rates of 75.4%
and 77.2% among GeneXpert® RR cases
phenotypically and genetically on Xpert® respectively.
Conclusively only 78.9% of RR cases by GeneXpert®
showed phenotypic resistance to rifampicin. Isoniazid
also showed a good agreement rate and sufficient gene
targets are included in the assay. Mutations in gyrA and
gyrB do not generalize the resistance among all
fluoroquinolones due to many differences in chemical
structures, absorbance and serum bioavailability of
drugs. Although Xpert® MDR-TB is a great addition to
prompt diagnosis of complex DR-TB cases more work
is needed to address the issues in finding genotypic
drug resistance for quinolones and all injectable drugs
for TB.
LIMITATIONS
The limitations of the study include observational study
design, purposive enrollment of patients and small
sample size.
CONCLUSIONS
The Xpert® MTB/XDR assay demonstrated greater
accuracy for drug-resistant pulmonary tuberculosis,
especially XDR-TB. However, more studies are needed
to validate the diagnostic performance of this new
modality.
CONFLICT OF INTEREST: None
FUNDING SOURCES: None
REFERENCES
1. World Health Organization (WHO). Global tuberculosis report
2020. 2020 [updated 2021, cited 2024]. Available from:
https://www.who.int/publications/i/item/9789240013131
2. Rehman S, Munir MK, Iqbal R, Saeed S. Pattern, diagnosis and
treatment outcome of extra pulmonary tuberculosis. Pak J Chest
Med. 2018;24(3):147-51.
3. World Health Organization (WHO). Global tuberculosis report
2021. 2021 [updated 2022, cited 2024]. Available from:
https://www.who.int/publications/i/item/9789240037021
4. Iqbal R, Munir MK, Rehman S, Saeed S. Drug resistant
tuberculosis: Pattern seen among patients visiting mayo
hospital, lahore. Pak J Med Res. 2018;57(4):132-7.
5. World Health Organization (WHO). Global tuberculosis report
2019. 2019 [cited 2024]. Available from:
http://www.who.int/tb/publications/global_report/en/
6. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T,
Lalloo U, et al. Extensively drug-resistant tuberculosis as a
cause of death in patients co-infected with tuberculosis and hiv
in a rural area of south africa. Lancet. 2006;368(9547):1575-80.
7. Pillay S, Steingart KR, Davies GR, Chaplin M, De Vos M,
Schumacher SG, et al. Xpert MTB/XDR for detection of
pulmonary tuberculosis and resistance to isoniazid,
fluoroquinolones, ethionamide, and amikacin. Cochrane
Database Syst Rev. 2022;5(5):CD014841. doi:
10.1002/14651858.CD014841.pub2.
8. Association of Public Health Laboratories (APHL). Drug
susceptibility testing for M. tuberculosis complex [Internet].
2020 [cited 2024]. Available from:
https://www.aphl.org/programs/infectious_disease/tuberculosis/
TBCore/DSTslides_updated_FINAL.pdf
9. Iqbal R, Tabbassum M, Shabbir I, Munir K, Khan S, Khan M.
Multi drug resistance tuberculosis: Pattern seen in last 13 years.
Pak J Med Res. 2011;50(1):10-4.
10. Yang JS, Kim KJ, Choi H, Lee SH. Delamanid, bedaquiline,
and linezolid minimum inhibitory concentration distributions
and resistance-related gene mutations in multidrug-resistant and
extensively drug-resistant tuberculosis in Korea. Ann Lab Med.
2018;38(6):563-8. Erratum in: Ann Lab Med. 2019;39(1):113.
doi: 10.3343/alm.2019.39.1.113.
11. Singh K, Sharma S, Banerjee T, Gupta A, Anupurba S.
Mutation detection and minimum inhibitory concentration
determination against linezolid and clofazimine in confirmed
XDR-TB clinical isolates. BMC Microbiol. 2022;22(1):236.
doi: 10.1186/s12866-022-02622-x.
12. World Health Organization. WHO announces updated
definitions of extensively drug-resistant tuberculosis [Internet].
www.who.int. 2021. Available from:
https://www.who.int/news/item/27-01-2021-who-announces-
updated-definitions-of-extensively-drug-resistant-tuberculosis
13. Li Z. The value of GeneXpert MTB/RIF for detection in
tuberculosis: A bibliometrics-based analysis and review. J Anal
Methods Chem. 2022;2022:2915018. doi:
10.1155/2022/2915018.
14. Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N,
Schumacher SG, et al. Xpert ultra versus xpert mtb/rif for
pulmonary tuberculosis and rifampicin resistance in adults with
presumptive pulmonary tuberculosis. Cochrane Database Syst
Rev. 2021(2):CD009593.
15. Shapiro AE, Ross JM, Yao M, Schiller I, Kohli M, Dendukuri
N, et al. Xpert mtb/rif and xpert ultra assays for screening for
pulmonary tuberculosis and rifampicin resistance in adults,
irrespective of signs or symptoms. Cochrane Database Syst
Rev. 2021(3):CD013694.
2015;59(9):5427
16. Cephide. Xpert MTB-XDR ENGLISH Package Insert 302-
3514 Rev C [Internet]. 2021 [cited 2024. Available from: Xpert
MTB-XDR ENGLISH Package Insert 302-3514 Rev C.fm
17. Willby M, Sikes RD, Malik S, Metchock B, Posey JE.
Correlation between gyra substitutions and ofloxacin,
levofloxacin, and moxifloxacin cross-resistance in
mycobacterium tuberculosis. Antimicrob Agents Chemother.
-34.
Diagnostic Performance of Xpert® MTB/XDR for Drug
8J Gandhara Nurs Alli Health Sci
JGNAHS
January - June 2025
LICENSE: JGMDS publishes its articles under a Creative Commons Attribution Non-Commercial Share-Alike license (CC-BY-NC-SA 4.0).
COPYRIGHTS: Authors retain the rights without any restrictions to freely download, print, share and disseminate the article for any lawful purpose.
It includes scholarlynetworks such as Research Gate, Google Scholar, LinkedIn, Academia.edu, Twitter, and other academic or professional networking sites.
18. Maitre T, Petitjean G, Chauffour A, Bernard C, El Helali N,
Jarlier V, et al. Are moxifloxacin and levofloxacin equally
effective to treat xdr tuberculosis? J Antimicrob Chemother.
2017;72(8):2326-33.
19. Al-Omar MA. Chapter 6 ofloxacin. Profiles Drug Subst Excip
Relat Methodol. 2009;34:265-98. doi: 10.1016/S1871-
5125(09)34006-6.
20. PubChem. Compound summary moxifloxacin [Internet].
Available from:
https://pubchem.ncbi.nlm.nih.gov/compound/Moxifloxacin.
21. Food and Drug Administration. LEVAQUIN® (Levofloxacin)
[Internet]. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/02
0634s040,020635s043,021721s007lbl.pdf.
22. Domenech P, Mouhoub E, Reed MB. Experimental
confirmation that an uncommon rrs gene mutation (g878a) of
Mycobacterium tuberculosis confers resistance to streptomycin.
Antimicrob Agents Chemother. 2022;66(3):e0191521. doi:
10.1128/AAC.01915-21.
CONTRIBUTORS
1. Muhammad Kashif Munir - Concept & Design; Data
Analysis/Interpretation; Critical Revision; Supervision; Final
Approval
2. Faiz Ahmad Raza - Data Analysis/Interpretation; Critical
Revision; Final Approval
3. Muhammad Adnan - Data Analysis/Interpretation; Drafting
Manuscript; Critical Revision; Final Approval
4. Sana Rehman - Data Analysis/Interpretation; Drafting
Manuscript; Critical Revision; Final Approval
5. Ruqyya Khalid - Drafting Manuscript; Critical Revision; Final
Approval
6. Asif Hanif - Data Acquisition; Critical Revision; Final
Approval
7. Muhammad Saqib Saeed - Concept & Design; Data
Acquisition; Critical Revision; Supervision; Final Approval
Diagnostic Performance of Xpert® MTB/XDR for Drug
JGNAHS
January - June 2025
LICENSE: JGMDS publishes its articles under a Creative Commons Attribution Non-Commercial Share-Alike license (CC-BY-NC-SA 4.0).
COPYRIGHTS: Authors retain the rights without any restrictions to freely download, print, share and disseminate the article for any lawful purpose.
It includes scholarlynetworks such as Research Gate, Google Scholar, LinkedIn, Academia.edu, Twitter, and other academic or professional networking sites.
18. Maitre T, Petitjean G, Chauffour A, Bernard C, El Helali N,
Jarlier V, et al. Are moxifloxacin and levofloxacin equally
effective to treat xdr tuberculosis? J Antimicrob Chemother.
2017;72(8):2326-33.
19. Al-Omar MA. Chapter 6 ofloxacin. Profiles Drug Subst Excip
Relat Methodol. 2009;34:265-98. doi: 10.1016/S1871-
5125(09)34006-6.
20. PubChem. Compound summary moxifloxacin [Internet].
Available from:
https://pubchem.ncbi.nlm.nih.gov/compound/Moxifloxacin.
21. Food and Drug Administration. LEVAQUIN® (Levofloxacin)
[Internet]. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/02
0634s040,020635s043,021721s007lbl.pdf.
22. Domenech P, Mouhoub E, Reed MB. Experimental
confirmation that an uncommon rrs gene mutation (g878a) of
Mycobacterium tuberculosis confers resistance to streptomycin.
Antimicrob Agents Chemother. 2022;66(3):e0191521. doi:
10.1128/AAC.01915-21.
CONTRIBUTORS
1. Muhammad Kashif Munir - Concept & Design; Data
Analysis/Interpretation; Critical Revision; Supervision; Final
Approval
2. Faiz Ahmad Raza - Data Analysis/Interpretation; Critical
Revision; Final Approval
3. Muhammad Adnan - Data Analysis/Interpretation; Drafting
Manuscript; Critical Revision; Final Approval
4. Sana Rehman - Data Analysis/Interpretation; Drafting
Manuscript; Critical Revision; Final Approval
5. Ruqyya Khalid - Drafting Manuscript; Critical Revision; Final
Approval
6. Asif Hanif - Data Acquisition; Critical Revision; Final
Approval
7. Muhammad Saqib Saeed - Concept & Design; Data
Acquisition; Critical Revision; Supervision; Final Approval
Diagnostic Performance of Xpert® MTB/XDR for Drug