TREATMENT OF MDR TB

1. TREATMENT MDR/XDR TB
PRESENTER : Maj S S RAWAL

2. INDEX
• DRUG RESISTANCE
• TREATMENT OF MONO /POLY DRUG
RESISTANCE , MDR/XDR TB
• BDQ
• MDR IN SPECIAL SITUATIONS

3. REFERENCES

4. DRUG RESISTANCE
• MONO RESISTANCE(MR) : biological specimenn
resistant to one first line anti-TB drug only
• POLY-DRUG RESISTANCE (PDR) : biological
specimen resistant to more than one first line
anti –TB drug, other than both INH and
rifampcin.
• MULTI DRUG RESISTENCE(MDR) : biological
specimen resistant to both INH and rifampcin ,
with or without resistance to other first line
drugs.

5. DRUG RESISTANCE
• RIFAMPICIN RESISTANCE (RR) :Resistance to
rifampicin , with or without resistance to INH.
• EXTENSIVE DRUG RESISTANCE (XDR): An MDR TB
case whose biological specimen is additionally
resistance to FQ( Ofloxacin,Levofloxacin and
Moxifloxacin) and a second line injectable
(kanamycin,Amikacin,or Capreomycin) from a
quality assured laboratory

7. RR & INH SENSITIVE/UNKNOWN
• Resistance to R with or without resistance to
other anti TB drugs excluding INH
• To be managed as MDR TB cases
• New patient- diagnosed as TB & RR by CBNAAT
• Repeat :
o CBNAAT
o LC –DST for H and second line drugs(SLD)
• Repeat CBNAAT –RR , start on MDR TB with INH
till DST

8. LC & DST
• LC – R sensitive
o Continue regimen for new TB cases
• LC- R resistance
o Refer patient to DR TB center committee for
clinical , biochemical and radiological assessment
o Decision for starting standard MDR treatment
o Continuing regimen for new TB case as per
response to treatment

9. INH RESISTANCE
RESISTANCE(LC) REMARKS
HIGH OMIT INH
LOW ADD HIGH DOSE INH
Kat G Mutation(LPA) OMIT INH
INH A Mutation(LPA) ADD HIGH DOSE INH , REPLACE EPAS

10. MDR TB/RR
TYPE OF TB CASE TREATMENT REGIMEN(IP) TREATMENT REGIMEN(CP)
RR + INH sensitive or
unknown
(6-9) Km Lfx Eto Cs Z E H (18) Lfx Eto Cs E H
MDR TB (6-9) Km Lfx Eto CsZ E (18) Lfx Eto Cs E
A TB patient whose biological specimen is resistant to R & H(quality assured lab)

11. XDRTB
TYPE OF TB CASE TREATMENT REGIMEN(IP) TREATMENT REGIMEN(CP)
XDR (6-12) Cm, PAS, Mfx, High
dose-H, Cfz, Lzd, Amx/Clv
(18)PAS, Mfx, High dose-H,
Cfz, Lzd, Amx/Clv
MDR TB whose biological specimen is additionally resistant to
oFQ( OFLOXACIN,LEVOFLOXACIN or MOXIFLOXACIN) &
o SLI (KANAMYCIN,AMIKACIN , or CAPREOMYCIN)

12. TYPE OF TB CASE TREATMENT REGIMEN(IP) TREATMENT REGIMEN(CP)
Rifampicin Sensitive INH
Resistant TB & DST of SEZ
not known
(3-6) Km Lfx R E Z (modify
treatment based on
baseline DST report to E, Z,
KM, CM, Lfx, Mfx)
(6) Lfx R E Z
MONO/POLY DRUG RESISTANT TB
Mono Drug resistant TB : Injectable SLD + FQ + Rifampicin + any two(H, E & Z)
Reported Baseline resistance to other FLDs : Inj SLD + FQ +Rifampicin +any FLD to
which patient is sensitive + one of remaining 4 groups

13. TYPE OF TB CASE TREATMENT REGIMEN(IP) TREATMENT REGIMEN(CP)
MDR or Rifampicin Resistant TB
+ Ethambutol resistance
OMIT
(6-9)Km Lfx Eto Cs Z (18) Lfx Eto Cs
MDR or Rifampicin Resistant TB
+ Pyrazinamide resistance
OMIT
(6-9)Km Lfx Eto Cs E (18) Lfx Eto Cs E
MDR or Rifampicin Resistant TB
+ Ethambutol + Pyrazinamide
resistance
(6-9)Km Lfx Eto Cs PAS (18) Lfx Eto Cs PAS
MDR or Rifampicin Resistant TB
+ Levofloxacin
(6-9)Km Mfx Eto Cs Z E PAS Cfz (18) Mfx Eto Cs E PAS Cfz

14. TYPE OF TB CASE TREATMENT REGIMEN(IP) TREATMENT REGIMEN(CP)
MDR or Rifampicin Resistant TB
+ Moxifloxacin
(6-9)Km Lfx Eto Cs Z E PAS Cfz (18) Lfx Eto Cs E PAS Cfz
MDR or Rifampicin Resistant TB
+ Resistance to all
Fluoroquinolones
(6-12)Km Eto Cs Z E PAS Cfz Lzd (18) Eto Cs E PAS Cfz Lzd
MDR or Rifampicin Resistant TB
+ Resistance to Km only
(6-9)Cm Lfx Eto Cs Z E (18) Lfx Eto Cs E
MDR or Rifampicin Resistant TB
+ Resistance to all SL
injectables
(6-12) Lfx Eto Cs Z E PAS Cfz Lzd (18) Lvx Eto Cs E PAS Cfz Lzd

15. MIXED RESISTANCE
• Consider oral drugs in following sequence of
preference:
– Pyrazinamide,Ethambutol,Ethionamide
– Cycloserine,,Pas,Clofazimine,Linezolid,
– Co-Amoxyclav, High dose INH and clarithromycin
• Regimen designing and modification is
prerogative of DR-TB centre committee only

16. BEDAQUILINE(BDQ)
• RNTCP introducing BDQ through conditional
access programmes at six cites in country initially.
• Basic Criteria for Patients to receive Bedaquiline:
– Age > 18years having pulmonary TB
• Additional criteria :
– Females should be non pregnant/effective non
hormone based birth control methods and
– willing to continue it during treatment period
– Controlled stable arrythmia can be considered after
cardiac consult

17. CENTRES APPROVED FOR BDQ
TREATMENT

18. GROUPS ELIGIBLE FOR BDQ
• MDR/RR-TB with resistance to all FQ
• MDR/RR-TB with resistance to all SLI
• XDR TB
– XDR TB(All FQ & SLI resistance)
– XDR TB(All FQ & any SLI resistance)
– XDR TB(All SLI &any FQ resistance)
– XDR TB(Any FQ & any SLI resistance)
• Treatment failure of MDR TB +FQ/SLI resistance
• Treatment failures of XDR TB

19. DOSAGE & ADMINISTRATION
• 400mg OD x first 2 wks
• 200 mg three times a week x following 22 wks
• Week 25 to end of treatment :continue other
second line anti TB drugs only

23. MDR-TB in patients with renal
impairment
• Renal insufficiency :
– longstanding TB disease itself,
– previous use of aminoglycosides or
– concurrent renal disease
– Dose adjustments required for drugs(AG,Ethambutol,
Quinolones, Cycloserine and PAS).
• BUN/Creat-
– prior to treatment initiation
– monthly for three months after treatment initiation
– then every three months
– whilst injection Kanamycin is being administered

24. MDR-TB in patients with pre-existing
liver disease
• MDR TB –
– Pyrazinamide, PAS and Ethionamide are
potentially hepatotoxic drugs
– FQ – hepatitis(rare)
– Increased risk :elderly, alcoholics and in patients
with pre-existing liver disease
• Patient on SLD , develops hepatitis rule out
other causes  mgmt similar to non MDR- TB
• Pretreatment LFT deranged  monthly LFTS

27. MDR TB IN SPECIAL SITUATIONS
• PREGNANCY :
– women of childbearing age who are receiving
MDR-TB therapy – advised to use birth control
measures because of the potential risk to both
mother and foetus
– OC Pills less effective – vomiting/drug interaction
– Preferred contraceptive measures –
Barriers/IUDs/Depot-medroxyprogesterone
– Role of obstetrician/ gyanecologists