Principles of treatment of drug-resistant tuberculosis

Posted by Master, Doctor Nguyen Ngoc Phu - ICU Doctor - Intensive Care Department - Vinmec Times City International General Hospital

Drug-resistant tuberculosis is a dangerous form of TB disease with side effects that seriously affect the patient's health. The treatment of drug-resistant TB is not only costly, but also lasts longer than with normal TB. Therefore, patients need to strictly adhere to the principles of treatment as directed by the doctor.

Patient is suspected of drug resistance while being treated for TB but the symptoms of fever, cough, sputum production do not improve or subside for some time and then reappear with increasing symptoms, the patient continues weight loss.
However, drug-resistant TB can be diagnosed in people who have never had TB, and the clinical symptoms of MDR-TB may not be that different from that of regular TB.
Based on the results of antibiogram or WHO-certified rapid diagnostic tests (Hain test, Xpert MTB/RIF...), diagnostic criteria for drug-resistant tuberculosis are determined as follows:
Drug-resistant TB: Resistant to only one other first-line anti-TB drug Rifampicin Multi-drug resistant TB: Resistance to two or more first-line anti-TB drugs but not to Rifampicin

Multidrug-resistant TB (MDR-TB): Concomitant resistance to at least two anti-TB drugs, Isoniazid and Rifampicin Pre-Super resistant: MDR-TB has additional resistance to any drug in the Fluoroquinolone class or to at least one of the three second-line injection of Capreomycin, Kanamycin, Amikacin, (but not both at the same time). Super-resistant (XDR-TB): MDR-TB has additional resistance to any of the fluoroquinolones and any of the three second-line injections (Capreomycin, Kanamycin, Amikacin).

New MDR TB: Patients with MDR TB who have no history of TB treatment or have been treated for less than 1 month (also called primary MDR TB). Recurrence: A patient with a history of previous TB treatment, concluded to be cured or completed, and is now diagnosed with MDR-TB. Formula I failure: Patients with MDR TB have a history of TB patients who have failed formula I in the past. Formula II failure: Patients with MDR-TB with a history of prior failure of formula II. Re-treatment after abandonment: A patient who has had a history of TB treatment before, was concluded to be abandoned, and is now diagnosed with MDR-TB. Other MDR-TB: A patient with MDR TB with unknown previous treatment results.

Multi-resistant TB with positive direct smear, positive culture (S+, C+). MDR-TB was negative, culture was positive (S-, C+). MDR-TB was positive by direct smear, culture was negative (S+, C-).

This is a test that gives results in about 2 hours with high sensitivity and specificity. AFB(+) cases should be tested for Xpert for resistance to rifampicin before giving first line anti-tuberculosis drug regimens.

All people with suspected TB symptoms must have a sputum test for pulmonary TB . In order to facilitate the patient's diagnosis on the day of visit, the test of 2 sputum samples on the spot should be applied instead of the 3 sputum sample test as before. The local sputum sample needs to be carefully instructed so that the patient can collect it properly, the time of sampling 1 and 2 should be at least 2 hours apart.

Culture on solid medium gives positive results after 3-4 weeks. Culture in liquid medium (MGIT - BACTEC) gave positive results after 2 weeks. Cases detected at provincial hospitals should be encouraged for culture testing when possible.

Pictures on chest X-ray suggestive of advanced pulmonary TB are infiltrates, nodules, caverns, can see images of traction in the upper half of the lung field, which can be unilateral or bilateral.
Chest X-ray has a high screening value with a sensitivity of over 90% for AFB (+) TB cases.

“The regimen should have at least 5 effective drugs, including 4 main second-line TB drugs (1 class A drug, 1 class B drug, at least 2 class C drugs) and pyrazinamide. In case there are not enough effective drugs to develop the above regimen, drugs of groups D2, D3 can be used to ensure enough 5 drugs. When a patient is resistant to FQs (group A) or second-line injections (group B), another drug should be substituted, but still following the same principles as for R/MDR-TB resistant patients. Using injectable drugs is still sensitive and can be used for a long time (12 months or during the course of treatment). If resistance to all injectable drugs is present, the use of drugs that the patient has never used or has not used injections is recommended. Using new generation Fluoroquinolone. Consider using new drugs according to World Health Organization recommendations and guidelines (Bedaquiline, Delamanid). Consider high-dose Isoniazid if anti-KAT results or low H-antibody results.

4-6 Km Lfx Pto Cfz Z H High Dose E / 5 Lfx Cfz Z E

8 Km (Cm) Lfx Pto Cs Z/12 Lfx Pto Cs Z

Principle: Replace resistant drugs with effective drugs (listed in the classification of drug-resistant TB drugs – WHO 2016) and still adhere to the general principle (at least 5 effective drugs, including 4 drugs). second-line TB drugs and pyrazinamide. D2, D3 drugs can be used to ensure all 5 drugs are effective)

Principle of protocol development: similar to pre-super resistant NB. However, because patients are already resistant to both FQs and second-line drugs, it is more difficult to choose an effective drug, especially for patients who have used most of the second-line drugs in the past. long-term availability or recurrence, failure of multidrug regimens. Priority should be given to the use of new drugs with the highest effectiveness, and at the same time, further strengthen the monitoring of treatment, management of adverse reactions, careful counseling for patients and family members to ensure compliance with the guidelines. 57 to achieve the best treatment outcome because this is the patient's last chance for treatment.

Enrolled subjects: R/MDR-TB resistant TB not eligible for standard regimens, including:
Meningococcal TB (depending on age, treatment history) Pregnant or lactating women Tuberculosis Severe multidrug-resistant lung: Intolerance, hypersensitivity, risk of drug toxicity (drug interactions) to any drug in the regimen. Some special cases need to adjust the dose of drugs or should not use some drugs: Patients with QT interval >=500 ms on electrocardiogram, liver failure, kidney failure, diabetes mellitus, epilepsy, neuritis optic nerve and peripheral nerve.
Principle: Replace intolerant or unsuitable drugs with other drugs and ensure “at least 5 effective drugs, including 4 effective second-line TB drugs (1 class A drug, 1 B, at least 2 class C drugs) and pyrazinamide. In case there are not enough effective drugs to develop the above regimen, drugs of groups D2, D3 can be used to ensure enough 5 drugs.

50 The TB Program is responsible for an adequate, ongoing supply of quality anti-TB drugs. Specifically:
Essential anti-TB drugs (row 1):
Essential anti-TB drugs (row 1) are: isoniazid (H), rifampicin (R), pyrazinamide (Z), streptomycin (S), ethambutol (E). ). Currently, WHO has recommended the addition of two first-line anti-TB drugs, rifabutin (Rfb) and rifapentine (Rpt). First-line essential anti-tuberculosis drugs should be stored at a cool temperature, away from moisture. Second-line anti-TB drugs:
Second-line anti-TB drugs mainly include the following drug classes:
A-Fluoroquinolones (FQs): Levofloxacin, Moxifloxacin, Gatifloxacin Group B-Second-line injection: Amikacin, Capreomycin, Kanamycin, Streptomycin(*) Group C-Other second-line drugs: Ethionamide, Prothionamide, Cycloserine, Terizidone Linezolid, Clofazimine. Group D - Complementary drugs (not in the main group): Bedaquiline, Delamanid, p-aminosalicylic acid, Imipenem-cilastatin, Meropenem, Amoxicillin-clavulanate, Thioacetazone. The situation of drug-resistant TB, especially multi-drug-resistant tuberculosis, is increasing rapidly in our country as well as in other countries around the world. Therefore, in addition to diagnosing the disease to have a timely treatment plan, adherence to the regimen and principles of drug-resistant TB is also extremely important. To do this requires close cooperation between the patient and the doctor, along with relatives and the social community to help the patient feel secure and strictly adhere to the treatment regimen to bring the best treatment effect. .