Linezolid Induced

Anemia In MDR TB
Patients

Oleh : dr. Dian Maulisa Fitriani

Pembimbing : dr. Parluhutan Siagian Sp. P(K), FISR

FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA

DEPARTEMEN PULMONOLOGI DAN KEDOKTERAN RESPIRASI
2021
 Introduction

Globally, it has been

estimated that 10.0 million
people had TB in 2019

And half a million (range

400 000–535 000) new cases
of MDR/RR-TB in 2019
 Introduction
When compared to patients
with drug susceptible Linezolid-related
disease, patients with hematological effects are
MDR/RR-TB require mild to moderate, while
treatment with regimens that reversible anemia usually
are longer and have a higher occurs after 4 weeks of
potential for adverse events treatment

Linezolid should be included

in the treatment of
MDR/RR-TB patients on
longer regimens (strong
Recommendation)
Below will be reported 3
cases of Linezolid induced
anemia in MDR-TB
Patients.
Case 1
 Case 1

A 49-years-old male patient presented History of anti tuberculosis

with shortness of breath, cough and loss treatment (+) 1st category in 2019

01 of appetite in two month. Loss of weight

10 kg within six month. He is an active
02 for 9 month based on clinical and
radiological finding
smoker with severe IB. History of
Diabetes Mellitus (+).

Patient had been tested for

sputum XpertMTB/Rif on 23
03 February 2021 with result MTB
(+) Rif Res
 Base Line Test
TEST RESULT
Haemoglobine 14,2
White blood Cell 7620
Platelete 182000
SGOT 81
SGPT 64
Calcium 8.5
Natrium 133
Potassium 4.4
Clorida 104
Ureum 21
Creatinin 0.99
Uric acid 4.3
T3 1.02
T4 9.56
TSH 1.44
Glucose adr 297
HBa1c 9,1%
 • Routine blood test showed
the patient was anemic
• Haemoglobin 3.2g%,
White Blood Cell
7.220/mm3, Platelate
134.000/mm3
• The longer MDR-TB
treatment was stopped

1st March 2021 27th May 2021 4th June 2021

• Started a longer regimen of • Intensive phase was

MDR-TB treatment
• Initial phase regimen was
Bedaquilin, Levofloxacin,
Linezolid, Clofazimin and
Cycloserin.
introduced again with the
following regimen of
Bedaquiline, Moxifloxacin,
Clofazimin, Cycloserin and
Pyrazinamide up until now.
Case 2
 Case 2

A 53-years-old male with

chief complain weak for one
week. History of cough and
loss of appetite in three
month. Loss of weight 6 kg
within three month. History
of bloody cough was not
found. He is an active
smoker with severe IB.
History of anti tuberculosis
treatment (+) 1st category in
2015 for 3 month based on Patient had been tested
clinical and radiological XpertMTB/Rif on 18 March
finding and the patient stop 2021 with result MTB (+) Rif
the treatment due to feeling Res
better.
 Base Line Test
TEST RESULT
Haemoglobine 12,3
White blood Cell 10870
Platelete 182000
SGOT 11
SGPT 10
Calcium 7.5
Natrium 132
Potassium 4.5
Clorida 92
Ureum 32
Creatinin 1.29
Uric acid 5.5
T3 0.5
T4 6.3
TSH 1.25
Glucose adr 266
HBa1c 9,1%
 Routine blood test showed
Haemoglobin 5.2 g% White
Blood Cell 6210/mm3,
Platelate 112.000/mm3
And treatment was stopped
30th March 2021 2nd June 2021
• Started on longer regimen of
MDR-TB treatment with initial
phase regimen was
Bedaquilin, Levofloxacin,
Linezolid, Clofazimin and
Cycloserin
Introduced again with regimen of
Bedaquiline, Levofloxacin,
Clofazimin, Cycloserin and
Pyrazinamide
6th June 2021 8th June 2021
After transfusion of PRC, blood
routine test was performed and
White blood Cell level was
decrease into 3.420/µL, with
Platelate 10.000/mm3 and
Haemoglobin 10,0 g%
Case 3
 Case 3

A 49-years-old Patient had been

History of anti
female patient tested sputum
tuberculosis
presented with XpertMTB/Rif on
treatment (+) 1st
shortness of breath 16 March 2021 with
category in 2020 for
worsening in 1 result MTB (+) Rif
6 month based on
week, cough and Res
clinical, radiological
loss of appetite in
and mcrobiologic
six month. Loss of
findings
weight 5 kg within 4
month.
 Base Line Test
TEST RESULT
Haemoglobine 12,2
White blood Cell 8170
Platelete 311000
SGOT 27
SGPT 18
Calcium 8,1
Natrium 134
Potassium 4.5
Clorida 100
Ureum 28
Creatinin 0.64
Uric acid 5.5
T3 0.45
T4 6.3
TSH 1.25
Glucose adr 77
 Case 3

21th March 2021 11th June 2021

6th June 2021

Start long regimen of MDR-TB Intensive phase was introduced

treatment with initial phase again with regimen of
Blood test showed Haemoglobin
regimen was Bedaquili, Bedaquiline, Levofloxacin,
6.3 g% White Blood Cell
Levofloxacin, Linezolid, Clofazimin, Cycloserin and
12900/mm3, Platelate
Clofazimin and Cycloserin Ethambutol
186.000/mm3
And treatment was stopped
Linezolid has been associated with In this report all cases had been
adverse hematological effect. The most reported above with anemia but,
common adverse effects include two patients (case 1 & 2) also had
diarrhea, nausea, and headache; less thrombocytopenia
common side
effects include hypertension,
lactic acidosis, and elevated
liver enzymes

Discussion
 Mechanism of Action of Linezolid

In-vitro studies suggest that Linezolid interacts with translation components that are responsible for mRNA bindings.
Linezolid and other oxazolidinones act by binding to bacterial 23S part of the 50S ribosomal subunit, Thereby,
hindering the formation of a 70S initiation complex and do not allow it to start translation process further. The 70S
initiation complex is crucial for bacterial translation and mitochondrial protein synthesis .
 Haematological Adverse Event in Linezolid

Primary mechanism of Bernstein et al., found in

myelosuppression is bone marrow’s patient
The mechanisms
inhibition of who taking linezolid
underlying Linezolid
mitochondrial protein which producing adequate
induced anemia are
synthesis via blocking numbers of
not clear, but the
initiation complexes that megakaryocytes to
vacuolated
affect mitochondrial maintain the normal
pronormoblasts
respiration platelet level in the blood.
suggested an anemia
which further leads to These findings indicate
similar to the
anemia. But various that there is no bone
mechanism for
studies also suggest that marrow suppression,
chloramphenicol-
drug induced rather there is some
induced
anemia is an immunological platelet
myelosuppression
immunological reaction destruction

In this cases all patient do not
had pre-existing anemia
before the linezolide threrapy,
but two patient (case 1 & 2)
had diabetes mellitus and
the heamoglobine after
linezolid therapy much
lower than patient in case 3.
Discussion
Linezolid use particularly All cases reported
prolonged linezolid above had anemia
courses (>14 days), has after 2 - 3 months of
been associated with starting the longer
hematological AEs, including regimen MDR-TB
anemia, leucopenia, therapy.
thrombocytopenia or even
pancytopenia.
All three Group A agents and at least one Group B agent should be
included to ensure that treatment starts with at least four TB agents likely
to be effective

If only one or two Group A agents are used, both Group B agents are
to be included. If the regimen cannot be composed with agents from
Groups A and B alone, Group C agents are added to complete it.

All cases reported above was introduced again longer regimen MDR-TB
without linezolid and linezolid was replaced with one of Group C
 Conclusion

Linezolid should be included in the treatment of MDR/RR-TB

patients on longer regimens

Linezolid use particularly prolonged linezolid courses (>14

days), has been associated with hematological AEs, including
anemia, leucopenia, thrombocytopenia or even pancytopenia

Continuous monitoring of blood parameters of patients

undergoing long‑term Lnz therapy on regular intervals should be
ensured.
Thank You !