Guideline: Management of Drug-Resistant Tuberculosis » Management Of Patients With Mono- and Poly-Drug Resistant TB



6.1. Introduction


Patients with mono- and poly-drug resistant strains of M. tuberculosis are not classified as MDR- TB or XDR-TB. Mono-resistance is defined as resistance to a single first-line anti-TB drug, while poly-drug resistance is resistance to two or more anti-tuberculosis drugs other than both rifampicin and isoniazid.


Routine testing for mono- and poly-drug resistant TB in all TB patients is not recommended as the majority of patients with mono- or poly-drug resistant TB will be cured with standard first-line chemotherapy.


6.2. Treatment of Patients with Mono- and Poly-Drug Resistant TB


With the exception of streptomycin, definite randomised or controlled clinical trials have not been conducted to determine the best treatment options for various types of drug resistance. Recommendations are based on evidence from the pre-rifampicin era, observational studies, general principles of microbiology and therapeutics in TB, extrapolation from anecdotal evidence and expert opinion.


The design of regimens for mono- and poly-drug resistant TB requires experience and should be done under supervision of the provincial DR-TB clinical review committees. The treatment history, DST pattern and the possibility of strains of M. tuberculosis having acquired additional resistance should be considered before deciding on an appropriate regimen.         


Some of the specific issues that should be considered when designing an appropriate regimen are described below.


6.2.1. Timing of DST Results



Because of the inevitable delay in culture and DST, the DST result that prompts a change in treatment may not accurately reflect the bacterial population at the time it is reported as it reflects the bacterial population at the time that the sputum specimen was collected.  The treatment regimens for mono- and poly-drug resistant TB assume that the pattern of drug resistance has not changed during this interval and should not be used if further resistance to any of the drugs is suspected.


6.2.2. Use of Pyrazinamide DST Results


DST results for pyrazinamide are unreliable and resistance to pyrazinamide should be assumed depending on the prior treatment history; in this case an alternative regimen should be used. However, pyrazinamide should be considered for inclusion in the regimen in certain circumstances as a considerable proportion of patients could still harbour pyrazinamide susceptible strains.


6.2.3. Development of Further Resistance


Further resistance should be suspected if the patient was on the functional equivalent of only one or two drugs for one month or more. For example, pyrazinamide is not regarded as a good companion drug to prevent resistance. If the patient was only receiving rifampicin and pyrazinamide (due to resistance to isoniazid and ethambutol), resistance to rifampicin may develop. Therefore, it is crucial to determine which functional drugs the patient received between the time of specimen collection and the time of initiation of the treatment regimen.


The regimens in Table XIII, which is a simplified table, are an adaptation of regimens suggested in the WHO guidelines.

All mono- and poly-drug resistant patients are to be recorded in the DR-TB register. All provinces that are still keeping them in the drug-susceptible register should put systems in place to address this matter.

Patients that are mono-drug resistant to rifampicin must be recorded as MDR-TB ‘not confirmed’.

Mono- and poly-drug resistant TB patients should be followed using:

  • TB microscopy  and TB culture every month during intensive phase until TB culture conversion.
  • TB microscopy and culture monthly during continuation phase
  • DST (repeated) if unsatisfactory clinical and biological progress after 3-4 months of treatment.