**13. Conclusion**

vaccine against MDR/XDR-TB and revealed that agglutinating virus of Japan/Heat-Shock-Protein65DNA+Interleukin-12-12DNA vaccine provided strong therapeutic efficacy in killing MDR/XDR-TB bacilli in mice and monkey models [73]. A recent experiment using MDR-TB monkey models which received normal and genetically altered Bacilli Calmette Gue′rin (BCG) vaccines demonstrated that these 2 groups of monkeys survived well compared to the control group [74]. Another study in XDR-TB mice model showed ability of interleukin-7 to kill the

Totally drug-resistant tuberculosis (TDR-TB or XXDR-TB) was recently defined as TB bacilli which resist to all first-line and the 6 second-line drugs (para-aminosalicylic acid, fluoroqui‐ nolones, aminoglycosides, thiamines, polypeptides, and cycloserine) [75]. Meanwhile, a recent report from the US-CDC listed 7 challenges that should be addressed before new terminology

**1.** The definition should not hinge on resistance to all drugs tested, because the number of

**2.** In vitro testing data suggest cross-resistance among different drugs within a class of drugs or closely related classes of drugs (e.g., polypeptides and aminoglycosides) is not 100%.

**3.** Research and reference laboratories in many countries do not test for resistance to the third-line drugs (linezolid, thioridazine, other phenothiazines, monobactams (merope‐ nem, imipenem), macrolides, metronidazole and other imidazoles, clofazimine, and

**4.** DST for several anti-TB drugs is not sufficiently reliable or reproducible; retesting the

**5.** There are several new anti-TB agents in development pipeline that will be prototypes for new classes of antimycobacterial drugs or add new chemical entities to existing class. **6.** Avoiding the unintended implication that patients with TDR-TB should not or cannot be

**7.** Global laboratory capacity for DST of *Mycobacterium tuberculosis* isolates remains limited [75]. Two cases of TDR-TB with controversies of terminology and treatment occurred in 2003 in Italy and firstly reported in 2007 [77]. Currently, in Thailand, patients with all anti-TB drug-resistance will be prescribed isoniazid alone for lifelong whereas no standardized treatment is recommended yet. During 21-22 March 2012, the WHO had convened a technical consultation to discuss the feasibility and implications of a definition to cover more advanced patterns of TB resistance than XDR-TB [78]. The WHO concluded that reports of severe patterns of anti-TB drug resistance ( worse than XDR-TB alone) are increasing whereas a new definition of anti-TB drug resistance beyond XDR-TB is not recommended [78]. This undefined resistance patterns contributed to technical difficulties

of TDR-TB should be considered for adopting [76], following are the challenges:

bacilli [74].

**12. Totally drug-resistant tuberculosis**

256 Tuberculosis - Current Issues in Diagnosis and Management

drugs tested varies widely between laboratories.

same isolate provides a different result in many cases.

amoxicillin/clavulanic acid).

treated.

As countries are purchasing and using second-line drugs, the likelihood of misuse and developing of TB-resistant strains increases. Currently, WHO and its partners have reached the phase of expanding MDR-TB control as a component of a comprehensive TB control programme. Launching in 2002, the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) expected that requests for second-line drugs for MDR-TB management should go through the Green Light Committee to prevent their misuse. The number of Green Light Committee-approved MDR-TB control programme is increasing rapidly as a result of main streaming of MDR-TB management into general TB control efforts. Expanding projects and accelerating evidence gathering are essential to further develop international policies. The TBendemic countries themselves and the ability of the technical agencies, as well as the donor community are the factors of future success to expand MDR-TB control programmes.
