Management and Experience of MDR TB Cases in Turkey

1. Management and Experience of MDR TB Cases in Turkey Dr.Gönenç Ortaköylü Yedikule Training and Research Hospital for Chest Diseases and Surgery

3. Yedikule Göğüs Hastalıkları ve Göğüs Cerrahi Merkezi E.A.H. • Number of beds : 349 (2008) • Hospitalized patients : 11 166 (2008) • Hospitalized TB patients : 693(% 6.2) (2008) • Mean hospit. time for TB pat. : 18 days

4. The number of TB inpatients according to years • Year TB (pulm+extra pulm) ÇİD-TB • 2004 1412 56 (% 3.9 ) • 2005 1651 43 (% 3.9 ) • 2006 1263 23 (% 1.8 ) • 2007 759 58 (% 7.6 ) • 2008 693 65 (% 9.3)

5. The approach to MDR TB cases • Since 2001, mdr tb cases have been discussed at mdr tb medical counsil. • Since 2004, the medications for MDR TB cases are have been supplied by ministery of health and our hospital.

6. The approach to MDR TB cases Diagnosing multidrug-resistant tuberculosis • Treatment for MDR TB is initiated in patients who remain or turn to positive after 5 months of TB treatment and are confirmed to be MDR TB by laboratory tests.

7. The approach to MDR TB cases Drug-sensitivity testing (Where? Why?) • 1-District laboratory Taksim • 2-İ.Ü.DETAE institute

8. The approach to MDR TB cases Drug-sensitivity testing(Where? Why?) • The ability to do cultures and DST for at least isoniazid (H), rifampin (R), Ethambutol (E) and streptomicine (S) should be performed. • Differentiation between NTM and MTB • DST for minor drugs is done in nearly all patients especially when primary MDR is highly probable.

9. The approach to MDR TB cases Principles used in the treatment of MDR TB • For every patient, definitive individualized treatment regimen(ITR) can be designed according to their DST and previous drug exposure. • The empiric regimen should be used until the DST results are available. • The empiric regimen consists of all drugs (5-7) believed to be sensitive to the strain so that the patient has a high probability of receiving at least four medications.

10. The approach to MDR TB cases Principles used in the treatment of MDR TB • The drug susceptibility test is interpreted and the definitive regimen is designed using a hierarchical algoritm according to drug effectiveness. • All medications from group I to which a strain is susceptible are used. • If H is susceptible at high concentration, it is used 900 mgX2 weekly.

11. The approach to MDR TB cases Principles used in the treatment of MDR TB • All patients receive an injectable agent (groupII).(SM or AMK) This should be continued at least 6 months following culture negativity. • All patients receive a quinalone (groupIII, usually Ofloxacine). • İf it is possible, all drugs from group IV (PAS, Prothio, CS) are added. • If four medicines to which the isolate is susceptible can not be obtained, the regimen is reinforced with groupV (Amx/ Clv, Clr,Cfz,Lzd)

12. The approach to MDR TB cases • Drugs are given to patients monthly from hospital pharmacy. • Clinical, bacteriological and radiological evaluations are performed. • Patients are evaluated for drugs side effects.

13. The approach to MDR TB cases • Treatment must continue at least 18-24 months following culture negativity. • Following discharge from hospital, patients are referred to their district tb dispanseries. • Except a few cases , DOT has not been provided yet.

14. At MDR TB council; 316 TB cases were discussed between 2001- 2008: MDR TB were diagnosed in 273 cases and individualized treatment regimen (ITR) was designed.

15. Table1. Characteristics of MDR TB patients ( n:273 ) (2001-2008)

16. Table 2.treatment outcome of MDR TB patients (n=193) (2001-2008)

17. n=26

18. Drug side effects (n:188) • Number of patients with side effects :108 (%57.4) • Number of drugs is stopped : 46 ( % 42.5) • Ototoxicity : 37 (% 35.2 ) • GIS complaints : 27 (% 25 ) • Psychiatric disorder : 26 (% 24 ) • Artrhralgia : 10 (% 9.2) • Hypothyroidy : 6 (% 5.5 ) • Skin eruption : 6 (% 5.5 ) • Convulsion : 5 (%4.6 ) • Hepatitis : 4 (%3.7 ) • Neuropathy : 3 (% 2.7 ) • Nephrotoxicity : 2 (% 1.8 )

19. Approach to defaulting on treatment • Patients who have been off therapy for longer than six months should be evaluated for active disease. • Active disease is present – start new course of treatment • Active disease is no present – clinical follow up and evaluation

20. Approach to defaulting on treatment • Patients who have been treated for less than 3 months • Smear positive or negative all patients should restart on a new course of treatment using their previous DST.

21. Approach to defaulting on treatment • Patients on treatment for 3-12 months • Smear positive- restart treatment and send for DST. • Smear negative - restart therapy with a regimen including an injectable until two cultures return. • A minimum of 24 months of therapy following negative culture.

22. Approach to defaulting on treatment • Interruption time longer than 12 months • Smear positive –send for DST and start a completely new course of treatment • Smear negative – there is no evidence of clinical deterioration, then oral medication can be restarted.

23. Approach to drug side effects (hearing loss) Irreversible Progression can be prevented by discontinuation of the offending agent. Continuation of injectable therapy despite hearing loss may be warranted in patients with signiricant resistance. • SM • KM • AMK • CM • Clr Hearing loss Tinnitus Capreomicin may replace an aminoglycoside agent. reduce dose (750 mg/day) or three times weekly

24. Conclusion • MDR-TB is a disease very difficult to treat and manage. • In Turkey, there is a need for a national patient registry system. • The national guideline should be prepared for appropriate treatment and disease management.

25. Thank you…