Monitoring
All patients should be monitored to assess response to treatment. Regular monitoring facilitates completion of treatment and permits identification and management of adverse reactions. Monthly monitoring of weight is important and used as the basis of dosage adjustment. Sputum smear examination is used to check the response of a patient to treatment. Sputum samples should be collected at each follow-up. The status of smear examination at the end of the intensive phase is a poor predictor of relapse.
Sputum Smear Monitoring in New and Retreatment Pulmonary Tuberculosis Patients
Sputum smear examination should be repeated at month 2, after the patient receives the last dose of intensive-phase treatment. If the sputum smear is positive at month 2, sputum smear examination should be repeated at month 5. If negative, no further sputum monitoring is needed. If sputum smear is positive at month 2 and patient does not show clinical and radiological improvement, culture and DST (line probe assay or Xpert MTB/RIF) should be done. Culture and DST at this stage will detect resistance without waiting until the 5th month to change the regimen. Xpert MTB/RIF can detect Rifampicin resistance in sputum smear-positive patients. Repeat Xpert MTB/RIF at the fifth or sixth month of treatment. If the NTP laboratory network is capable of rapid molecular tests for first-line DST, first-line LPA should be done for non-converters of drug-susceptible TB regimens who are still Rifampicin-susceptible in Xpert MTB. Treatment failure is considered if MDR-TB is detected (smear- or culture-positivity) at any point or if sputum smear is still positive at months 5 or 6. Change of treatment is recommended.
Possible Reasons for a Positive Sputum Smear at the End of Intensive Phase
Possible reasons for a positive sputum smear at the end of the intensive phase include poor supervision and patient compliance with the initial phase of therapy; poor quality of anti-TB agents; underdosage; a patient having extensive cavitation and a heavy bacillary load that leads to slow resolution; the presence of comorbid conditions that interfere with treatment adherence or response; the presence of MDR-TB; and non-viable bacteria remaining in microscopy.
Managing Side Effects of Anti-TB Drugs
A patient who will have minor adverse effects is advised to continue the regimen and be given symptomatic treatment. A patient who will have major adverse effects is advised to discontinue the drug and be referred to a clinician/hospital for further evaluation and management.
Common Side Effects
Cutaneous Reactions
For cutaneous reactions, responsible drugs include Streptomycin, Isoniazid, Rifampicin, and Pyrazinamide. For itching without rash and no other obvious cause: Give the patient antihistamines and moisturizers and continue TB treatment while observing the patient. If a rash develops, discontinue all anti-TB drugs. Once resolved, anti-TB drugs should be re-introduced one by one at a lower dose and then gradually increased over 3 days.
Deafness or Dizziness or Decreased Urine Output
The responsible drug for deafness, dizziness or decreased urine output is Streptomycin. Discontinue the drug if these symptoms appear.
Drug-induced Hepatitis
For drug-induced hepatitis, responsible drugs include Isoniazid, Pyrazinamide, and Rifampicin. Rifampicin can also cause asymptomatic jaundice without evidence of hepatitis. It is advised to discontinue all anti-TB drugs. If the patient is severely ill and unsafe to stop TB drugs, non-hepatotoxic agents (eg Streptomycin, Ethambutol and a fluoroquinolone) may be used. Once resolved, anti-TB drugs should be reintroduced one by one, starting with Rifampicin and then Isoniazid after 3-7 days. If hepatitis with jaundice occurs during the intensive phase and then resolves, the same drugs should be restarted, but Pyrazinamide should be replaced with Streptomycin to complete the 2-month initial therapy, followed by Rifampicin and Isoniazid for the 6-month continuation therapy. If hepatitis with jaundice occurs during the continuation phase and then resolves, Isoniazid and Rifampicin should be restarted to complete the 4-month continuation therapy.
Shock, Purpura, or Acute Renal Failure
The responsible drug for shock, purpura or acute renal failure is Rifampicin. Discontinue the drug.
Monitoring MDR-TB Patients
Close monitoring is important during treatment of MDR-TB patients. Response to treatment should be monitored clinically, radiographically, and bacteriologically. A sputum smear and culture should be done monthly until the patient has smear and culture conversion (two consecutive smears and cultures are negative). Repeat DST is recommended when cultures remain positive after 3 months of therapy or in the case of bacteriological reversion from negative to positive at any time during treatment. After conversion, bacteriological monitoring is advised monthly for smears and quarterly for cultures. Sputum culture at 6 and 12 months after treatment completion is advised for patients on longer regimens to ensure sustained cure. Monthly follow-up is advised until sputum conversion and then every 2-3 months thereafter. Weight should be recorded monthly.
Monitoring During TPT
Healthcare practitioners who are managing patients undergoing TPT should monitor all patients, prior to and during therapy, for the presence of an active TB disease; educate patients, parents or caretakers regarding side effects and remind them to immediately undergo medical consultation upon noticing any signs and symptoms of such, especially if they present as rashes, decrease in blood pressure and platelet count, or drug allergy-related; evaluate patients for treatment compliance and presence of side effects every month, stressing the importance of recognizing adverse effects every follow-up consultations; request for liver function tests (or at least an aspartate aminotransferase [AST] test) in patients with liver disease, HIV, those who have given birth in ≤3 months, alcoholics, drug users using injection paraphernalia, or those who are taking medications that cause certain effects when taken with other drugs; facilitate blood tests for patients with abnormal results and those who are prone to having hepatic disorders on follow-up consultations (the 3 HP regimen should be temporarily discontinued if the AST result is ≥5x the upper limit of the normal with no concomitant symptoms or ≥3x the upper limit of the normal with accompanying symptoms); and in any type of adverse reaction, the patient should be given appropriate medical intervention. In severe reactions, 3 HP is discontinued, while in those that are minimal to moderate (as evaluated by a healthcare provider), 3 HP may be resumed under vigilant watch.
Complications
Tuberculosis Patients with HIV
Whether CD4 cell count is increased, decreased, or normal, antiretroviral treatment (ART) should be initiated. The WHO recommends that TB patients living with HIV should receive at least the same duration of TB treatment as HIV-negative TB patients. ART is introduced in the therapy within the first 8 weeks after starting tuberculosis treatment. Introduced within the first 2 weeks after starting TB treatment only if the patient is significantly immunocompromised (eg CD4 cell count below 50 cells/mm3). In those with concomitant TB meningitis, side effects that are more severe were observed when ART is introduced early than when it was initiated after 8 weeks (2 months) of TB therapy. For patients who have pulmonary tuberculosis, that is drug-susceptible and under ART therapy, a 6-month duration is preferred rather than 8 months or more with regard to TB treatment completion. The patient may be eligible for treatment with a shorter all-oral Bedaquiline-containing regimen (eg BPaLM) for MDR-TB, but a combination with Ritonavir should be avoided or administered with caution. The 4-month Rpt-Mfx regimen, as recommended by the CDC and WHO can also be used in persons with HIV who have CD4 counts ≥100 cells/mm3 and are receiving or planning to initiate Efavirenz as part of their ART in the absence of any other known drug-drug interactions.
Patients with Tuberculous Meningitis
In patients with tuberculous meningitis, corticosteroids (Dexamethasone or Prednisolone) should be added to the treatment and tapered for 6-8 weeks.
Patients with Tuberculous Pericarditis
In patients with tuberculous pericarditis, an initial adjuvant corticosteroid may also be added in the treatment.
Patients with Latent TB Infection
In patients with latent TB infection, preferred regimens are Rifamycin-based regimens (because of their high treatment completion rates, safety, and effectiveness) as follows:
- Isoniazid-Rifapentine combination administered once weekly for 3 months is strongly recommended for adults and children >2 years old and in HIV-positive individuals
- Rifampicin daily for 4 months is recommended for HIV-negative adults and children of all ages;
- Isoniazid-Rifampicin combination daily for 3 months is recommended for adults and children of all ages and in HIV-positive individuals
Alternative recommended regimens (considered less effective due to higher toxicity risk and lower treatment completion rates) include:
- Isoniazid daily for 6 months which is strongly recommended for HIV-negative adults and children of all ages and conditionally recommended for HIV-positive adults and children regardless of age
- Isoniazid daily for 9 months which is conditionally recommended for both HIV-negative and HIV-positive adults and children regardless of age
This may be given via DOT or self-administered in patients ≥2 years of age.