This document discusses multi-drug resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB). It defines MDR TB as infection by Mycobacterium tuberculosis resistant to at least isoniazid and rifampin, and XDR TB as MDR TB additionally resistant to fluoroquinolones and injectable second-line drugs. Treatment of MDR TB requires using at least four effective drugs, including an injectable agent, while treatment of XDR TB uses third-line drugs to ensure four effective agents. Adherence to multi-drug regimens is important for preventing further resistance.

2. Multi Drug Resistant
(MDR) Tuberculosis

3. Antituberculous Therapy
• First-line agents : Isoniazid , Rifampin , Ethambutol
, Pyrazinamide.
• Second-line agents: Fluoroquinolones & injectable
Aminoglycosides:
( Kanamycin , Amikacin ,Streptomycin) & Capreomycin.

4. Antituberculous Therapy
• less effective second line agents :
Ethionamide , Cycloserine, Aminosalicylic Acid
Alternative agents : Clofazimine, Amoxicillin –
Clavulanate , Linezolid , Carbapenems,
Thioacetazone, & Clarithromycin

5. OUTLINE
1. Drug resistant TB (one drug).
2. Multi drug resistant TB ( tow drugs) .
3. Extensive drug resistant TB
( four drugs or more ).

6. Definitions
1. Drug resistant TB:
M.Tuberculosis that is resistant to one of the
first-line anti TB :
Isoniazid , Rifampin, Pyrazinamide ,
Ethambutol, Streptomycin.

7. Definitions
2. Multi drug resistant TB (MDR TB) :
M.Tuberculosis that is resistant to two
most potent first-line agents Isoniazid
& Rifampin.

8. Definitions
3. Extensively drug-resistant TB (XDR TB) :
M.Tuberculosis that is resistant to at least:
Isoniazid , Rifampcin, Fluoroquinolones.
plus one injectable agent :
( Amikacin , Kanamycin or Capreomycin ).

9. TB History
• Drug resistance first
noted in the 1940s
to streptomycin.
• Multi-drug regimens to
decrease the risk of
drug resistance.

10. TB History
• Outbreak of MDR TB in mid
1990s (HIV).
• China ,USA , Spain ,Italy.

11. Tugela Ferry
• Tugela Ferry
• International alarm first
surfaced in 2006 with the
detection of a large cluster
of cases of XDR TB.
• 1539 individual patients with
suspected TB
• 542 patients positive TB.
• 221 patients ( 41%) MDR
and 53 XDR.

12. Tugela Ferry
• Important observation :
• All 44 of the 53 patients
with XDR TB were HIV
seropositive and with
median CD4 count was
63 cells/microL. Viral
loads were not available.
• 52 out of 53 of the
patients died.
• 70 % of patient died
within 30 days from the
time of sputum collection.

13. Tugela Ferry
• Two healthcare workers were among the XDR
cases.
• Resistance to all of the six drugs tested at the
time
( isoniazid , rifampin , ethambutol , streptomyci
n ,ciprofloxacin and kanamycin ).

14. MDR VS XDR
• Descriptive analysis of US TB cases
reported from 1993 to 2007, a total of 83
XDR TB cases:
1. XDR TB cases more disseminated TB
disease.
2. 26 XDR TB cases (35 %) died during
treatment, of whom 21 (81 %) were known
to be HIV-infected.
3. Mortality was higher among XDR TB.

15. DIAGNOSIS
• The clinical manifestations and radiographic features
of drug resistant TB are comparable to those of drug
susceptible disease !!

16. A careful history must be obtained !!!

17. HISTORY
• Demographic and historical features that
should raise the suspicion of drug resistant TB
include :
1-Previous treatment for active TB, self
administered ,or treatment failure.

18. HISTORY
2-HIV infected patients ( malabsorption, drug
interactions ART ).
3- TB in a region with known high rates of drug
resistance.
4- Failure to respond to empiric therapy,
particularly if adherence has been documented.

19. LAB TEST
• Culture and Sensitivity testing of sputum.
Rapid testing (Nucleic acid tests):
• -GeneXpert MTB/RIF accuracy for rifampin resistance
98 % ( in 2 hours ).
• MTBDRplus detecting rifampin and isoniazid resistance
mutations 99 % sensitive and specific (4days).
• Direct DNA sequencing analysis of sputum.

20. LAB TEST
• These assays hold promise for the early and
rapid detection.
• Limitations: cost effective & identification
only Rifampin & Isoniazid.

21. TREATMENT OF MONORESISTANT TB
1- INH monoresistant :
• Rifamycin , Pyrazinamide & Ethambutol
(6-9 months) or 4 months after culture
conversion.
which is based on trials conducted by the Hong Kong
Chest Service/British Medical Research Council; these demonstrated
success rates of 95 to 98 percent among 107 patients with INH-
resistant disease

22. TREATMENT OF MONORESISTANT TB
2.Rifampin monoresistance:
• Less common than Isoniazid resistance.
• More in HIV patients (CD4 cell counts <100/microL).

23. TREATMENT OF MONORESISTANT TB
• Isoniazid , Pyrazinamide plus Streptomycin
for 9 months. This regimen has shortest
duration, & good efficacy.
OR
• Isoniazid , pyrazinamide plus ethambutol for at
least 12 months.
• Adding streptomycin or quinolone in first 3
months ??

24. TREATMENT OF MONORESISTANT TB
3-Pyrazinamide monoresistance:
• 9 months regimen of Isoniazid & Rifampin .
• Success rate >96 % .

25. TREATMENT OF MDR
GOAL!
• Include first-line agents plus whatever additional
drugs are necessary to ensure that at least four
drugs active against the most prevalent drug
resistant strains are included in the regimen
• Injectable agent is a must.

26. Treatment XDR
GOAL !
at least four drugs active
• Use of third-line agents: Linezolid ,
Clofazimine, Amoxicillin-Clavulanate ,
Meropenem-clavulanate or or Clarithromycin .

27. • Surgery:
Is effective for patients with localized pulmonary
disease which can be completely resected.

28. PREVENTION MDR TB
• Appropriate therapy.
• Guarantee adherence to therapy.
• HIV control and prevention .

29. TAKE HOME MESSAGE
1. HX of HIV should rise suspicion of MDR .
2. MDR & XDR RX 4 active drug.
3. Multi drug regimen with adherence decrease further
genetic mutation and resistant.

30. THANK YOU
Done by: AMER ALBOUSH
MEDICAL INTERN
Umm Al-Qura University

31. Questions ?