short treatment

1. Management of Drug
Resistance-TB
(DR-TB) Short Regimen
LUCKY MUNSAKA
(Dip.Pharm)
SUPERVISOR : MRS UCHIZI CHOLA
(MSc.Epi, B.Pharm, Dip.Pharm)

2. Outline
• Introduction
• Drug resistance - Types and Definitions
• Management of DR-TB ( latest updates)
• Criteria(Eligibility) for short regimen
• Subgroups for consideration
• Monitoring parameters
• Conclusion
• Take home massage
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3. Introduction
• In 2015, 10.4 million people globally developed tuberculosis (TB) and 1.4
million died, with TB remaining one of the top 10 causes of death
• Of the estimated 580,000 people newly eligible for multi-drug resistant TB
(MDR-TB) treatment, only 125,000 (20%) were enrolled on treatment.
• MDR-TB is a growing problem in Zambia. The WHO Global TB Report
2016 estimated there were 1,500 MDR/rifampicin resistant TB (RR-TB)
cases among notified pulmonary TB cases in Zambia in 2015; in the same
year, only 196 patients were laboratory confirmed with MDR/RR-TB, and 99
patients were started on treatment.
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4. Intro cont..
• In May 2011, the WHO produced policy guidance recommending
GeneXpert MTB/RIF (Xpert MTB/RIF) as the preferred rapid molecular
diagnostic test for rifampicin resistance (RR) for all patients with signs and
symptoms of TB
• In May 2016, the WHO issued recommendations on the use of a shorter
DR-TB treatment regimen [5] for uncomplicated MDR-TB treatment.
• Approximately 1 person dies of TB in India each minute (Times of
India, August 29, 2003).
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5. 5

6. Definitions
• Rifampicin-resistant tuberculosis (RR-TB) : a clinical isolate confirmed
to be M. tuberculosis resistant to rifampicin, with or without resistance to
other anti-TB drugs.
• Mono-drug resistant tuberculosis : a clinical isolate confirmed to be M.
tuberculosis that is resistant to one first-line anti-TB drug only.
• Multi-drug resistant tuberculosis (MDR-TB) : a clinical isolate
confirmed to be M. tuberculosis that is resistant to at least both isoniazid
and rifampicin.
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7. Definitions cont…..
• Poly-drug resistant tuberculosis (PDR-TB): a clinical isolate confirmed
to be M. tuberculosis that is resistant to more than one first-line anti-TB
drug (other than both isoniazid and rifampicin).
• Total Drug Resistance (TDR) : is Resistance to all first-line anti-TB drugs
(FLD) and second-line anti-TB drugs (SLD) that were tested.
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8. Drug resistance
• When drug resistance is demonstrated in a patient who has never received
anti-TB treatment previously, it is termed primary (Initial) resistance, i.e. TB
patient’s initial M.TB population resistant to drugs
• Secondary (Acquired) resistance is that which occurs as a result of specific
previous treatment, i.e. Drug-resistant M. TB in initial population, selected by
inappropriate drug use (inadequate treatment or non-adherence)
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9. 9

10. Management
1. Diagnosis
• In Zambia, the diagnosis of MDR TB is done using
I. Xpert MTB/RIF
II. Line Probe Assay (first and second line)
III. culture and phenotypic Drug Susceptibility Test (DST).
• Xpert MTB/RIF is recommended as the first diagnostic test in all adults
and children with signs and symptoms of TB where available
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11. Management cont…
2. Treatment
• Total treatment duration is 9-12 months
• Intensive phase 4-6 months depending on culture convention
• If culture convention occurs in 2nd month intensive phase is 4 months
• If no culture convention intensive phase is for 6 months
• Continuation phase 5 months
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12. Medicines recommended for the
treatment of RR-TB and MDR-TB
Group A. Fluoroquinolones2 Levofloxacin
Moxifloxacin
Lfx
Mfx
Group B. Second-line
injectable agents
Amikacin
Capreomycin
Kanamycin
Am
Cm
Km
Group C. Other core second-
line agents2
Ethionamide / prothionamide
Cycloserine / terizidone
Linezolid
Clofazimine3
Eto / Pto
Cs / Trd
Lzd
Cfz
Group D. Add-on agents
(not part of the core MDR-TB
regimen)
D1 Pyrazinamide
High-dose isoniazid
Ethambutol
Z
HHD
E
D2 Bedaquiline
Delamanid
Bdq
Dlm
D3 para-aminosalicylic acid
Imipenem–cilastatin
Meropenem + amoxicillin-
clavulanate4
(Thioacetazone)5
PAS
Ipm
Mpm + Amx-Clv
(T)
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13. Management cont…
Standardized shorter DR-TB regimen
4-6 Km-Mfx-Cfz-Eto-Z-E-HHD / 5 Mfx-Cfz-E-Z
Add vitamin B6 100 mg/day in intensive phase
• Recommendation applies to adults, children, PLHIV
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14. Patients eligible for the shorter DR-TB
treatment regimen
• Patients with DR-TB who have not been previously treated with
second line drugs;
• Patients with low risk for resistance to FQs and/or SLI or with
DST results excluding resistance to FQ and/or SLI;
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15. • Children ≤ 8 years of age, HIV infected patients, or patients with non-
severe forms of EPTB who;
have not been previously treated with SLD;
have a low risk of resistance to FQ and/or SLI;
in the absence of bacteriologic confirmation of DR-TB, who are clinically
diagnosed with DR-TB based on risk factors (e.g. close contact of a known
DR-TB patient)
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16. Patients not eligible for the shorter DR-
TB treatment regimen
• Patients with confirmed resistance to FQ or SLI by either SL-LPA
or phenotypic DST
• Patients with suspected resistance to FQ or SLI based on contact
with patient with this resistance pattern or other risk factor
• Confirmed resistance or suspected ineffectiveness to a medicine
in the shorter regimen (excluding isoniazid). This includes
resistance to either the fluoroquinolones (FQ), the second line
injectable agents (SLID), or both (either pre-XDR-TB or XDR-TB)
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17. • Patients with exposure to SLD for >1 month (e.g. patients already on
treatment with a conventional DR-TB treatment regimen for more than a
month or patients with history of previous DR-TB treatment)
• Patients with intolerance to any of the medicines in the shorter treatment
regimen
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18. • Pregnant women
• Patients with extra-pulmonary TB; an exception be make for patients with
TB pleural effusion and children with TB lymphadenitis, who may be
considered for the shorter treatment regimen
• Patients with higher risk of treatment failure, such as severe TB disease
(e.g. multiple cavities, extensive parenchymal damage) or a severely low
BMI
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19. Subgroups for considerations for shorter
regimen
1. Rifampicin-resistant TB (RR-TB) without MDR-TB : All patients –
children or adult – with RR-TB in whom isoniazid resistance is not
confirmed may be treated with the shorter MDRTB treatment regimen.
2. Resistance additional to MDR-TB : For patients infected with
strains known or strongly suspected of being resistant to one or more
drugs in the shorter MDR-TB treatment regimen (e.g. pyrazinamide)
it is recommended not to use the shorter regimen until ruled out by
DST
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20. Subgroups cont…
3. People living with HIV : Need to be given the same consideration for
treatment with the shorter MDR-TB treatment regimen as HIV seronegative.
4. Children : with confirmed RR-TB / MDR-TB be given same consideration
for treatment with a shorter MDR-TB treatment regimen as adults.
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21. Subgroups cont…
5. Pregnant women : it is recommended that a longer
individualized regimen be used which can allow the inclusion of
four or more effective second-line TB medicines with no known
teratogenic properties
6. Extra pulmonary disease : No recommendation is thus
possible at this stage to use the shorter regimen in patients with
extra pulmonary MDR-TB/RR-TB
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22. Monitoring parameters for drugs
used
DRUG SIDE EFFECTS MONITORING PARAMETER
Clofazimine (Cfz)  Orange/red discoloration of skin,
conjunctiva, cornea and
body fluids.
Symptomatic monitoring.
Ethambutol (Emb)  Retrobulbar neuritis (dose-related
–exacerbated during renal failure)
Baseline and monthly visual acuity
and colour discrimination
Ethionamide (Eto)  Gastrointestinal upset and
anorexia
 Hepatotoxicity.
 Gynaecomastia, hair loss, acne,
impotence,
 menstrual irregularity, and
reversible hypothyroidism
 thyroid stimulating hormone for
evidence of hypothyroidism
therapeutic drug monitoring
required if
malabsorption is suspected.
 LFTs
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23. Isoniazid (Inh)  Hepatitis (age-related).
 Peripheral neuropathy.
 Hypersensitivity reactions.
For patients receiving multiple
TB drugs or other hepatotoxic
drugs, or with underlying liver
disease
(including viral hepatitis), baseline
liver function testing is
recommended
Kanamycin (Km)  Nephrotoxicity
 Ototoxicity (hearing loss) and
vestibular toxicity
 Monitor renal function by
documenting creatinine at least
monthly
 Question patient regularly
about vestibular complaints
and perform serial vestibular
exams
Moxifloxacin (Mfx)  Nausea and diarrhea.
 Headache and dizziness.
Symptomatic monitoring.
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DRUGS SIDE EFFECTS MONITORING PARAMETERS

24. Pyrazinamide (Pza)  Gout (hyperuricaemia)
and arthralgias.
 Hepatotoxicity.
 Rash.
 Photosensitivity.
 Gastrointestinal
upset.
Monitor transaminases
and uric acid.
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DRUGS SIDE EFFECTS MONITORING PARAMETERS

25. Conclusion
• A shorter MDR-TB treatment regimen is recommended under
specific conditions
• Drugs used in the design of longer MDR-TB treatment regimens
are now regrouped differently based upon current evidence on
their effectiveness and safety.
• Clofazimine and linezolid are now recommended as core second-
line medicines in the MDR-TB regimen
• p-aminosalicylic acid is an add-on agent.
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26. Conclusion cont…
• DR-TB treatment is recommended for all patients with RR-TB,
regardless of confirmation of isoniazid resistance
• Specific recommendations are made on the treatment of children with
RR-TB or MDR-TB
• Clarithromycin and other macrolides are no longer included among
the medicines to be used for the treatment of MDR/RR-TB
• Evidence-informed recommendations on the role of surgery are now
included
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27. Carry Home Message
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Better to Prevent DR-TB
Regular Drugs
Appropriate Dosages
Full
Duration
Health Education
Direct Supervision
5/16/2019

28. References
1. World Health Organization Global Tuberculosis Report 2016.
2. World Health Organization. Automated Real-time Nucleic Acid
Amplification Technology for Rapid and Simultaneous Detection of
Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System 2011.
3. World Health Organization treatment guidelines for drug-resistant
tuberculosis: 2016 update.
4. World Health Organization. Active tuberculosis drug safety monitoring
and management (aDSM). Framework for implemention. November 2015.
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