Types of antituberculosis drugs for the treatment of tuberculosis

Although it takes a long time, tuberculosis (TB) can be completely cured by taking the right medication and always obeying the rules for taking TB medicine. The reason is, if TB treatment fails, this disease will be increasingly difficult to cure. TB treatment itself consists of two stages using a combination of several anti-biotic drugs.

What types of antibiotics are used for TB and how are the rules for taking them? Check out the explanation of TB treatment in more detail in the following review.

Two stages of TB treatment in Indonesia

Tuberculosis occurs when the bacteria that cause tuberculosis, namely Mycobacterium tuberculosis, actively infecting or multiplying in the body (active TB). Tuberculosis that attacks the lungs can be cured by undergoing treatment for 6-9 months.

The form of TB treatment in Indonesia consists of 2 stages, namely the intensive treatment stage and the follow-up treatment.

Reporting from the National Drug Information Center, during the two stages of treatment, patients take antibiotics and synthetic anti-infection drugs.

Treatment is carried out with a combination of several types of antibiotics called the anti-tuberculosis class. The drugs used work for 3 clinical functions, namely to kill, sterilize (cleanse the body), and prevent bacterial resistance.

1. The intensive stage

At the stage of intensive treatment, the patient needs to take TB medicine every day for a period of 2 months. Intensive treatment is aimed at reducing the number of bacteria that cause tuberculosis and stopping the infection so that patients can no longer transmit the disease.

Most of the patients with the status of transmitting the infection have the potential to become non-infectious (non-infectious) within 2 weeks if they are properly treated with intensive treatment. The types of TB drugs used in this stage can vary, depending on the treatment regimen that is tailored to the patient category.

Tuberculosis patient category

The patient category itself is determined from the history of treatment and the results of the AFB (sputum examination). In general, there are 3 categories of TB patients, namely:

• Category I new cases
  Patients who are smear positive but have not received antituberculosis treatment for less than 4 weeks, or smear negative with severe extrapulmonary TB (a bacterial infection that attacks organs other than the lungs).
• Category II relapse
  Patients who have been declared cured after completing treatment, but smear positive results.
• Category II failed cases
  Patients with AFB remained positive or came back positive after 5 months of treatment.
• Category II treatment was interrupted
  Patients who have been treated, but stop and come back with a positive smear or radiological results showing active TB status.
• Category III
  Patients with positive X-rays with mild extrapulmonary TB conditions.
• Chronic case patient
  Patients with AFB remained positive after re-treatment.

Patients who are smear negative and have extra-pulmonary TB can get a smaller amount of the drug at this stage.

2. Advanced stage

In the advanced stages of treatment, the number and dose of TB drugs given will be reduced. Usually only 2 types of drugs. However, the duration is even longer, which is about 4 months in patients with the new case category.

The follow-up stage of treatment is important to ensure that the dormant bacteria are completely removed from the body, thereby preventing TB symptoms from recurring.

Not all tuberculosis patients need to undergo intensive and follow-up treatment in a hospital. However, for severe cases (experiencing severe shortness of breath or symptoms of extra pulmonary TB), patients need to be hospitalized in the hospital.

The types of TB drugs first line

There are 5 types of TB drugs that are commonly prescribed, namely:

• Isoniazid
• Rifampicin
• Pyrazinamide
• Ethambutol
• Strptomycin

The five types of TB drugs above are commonly called primary drugs or first-line drugs.

In each stage of TB treatment, the doctor will give a combination of several anti-tuberculosis drugs. The combination of TB drugs and the dosage is determined by the condition and category of TB patients so that they can vary.

The following is an explanation of each of the first-line TB drugs:

1.Isoniazid (INH)

Isoniazid is a type of anti-tuberculosis that is most effective in killing the bacteria that cause tuberculosis. This drug can kill 90% of TB germs within a few days at the intensive treatment stage.

Isoniazid is more effective at killing bacteria that are actively developing. This drug works by interfering with manufacture mycolic acid, namely compounds that play a role in building bacterial walls.

Some of the side effects of the TB drug isoniazid include:

• Neurological effects, such as visual disturbances, vertigo, insomnia, euphoria, changes in behavior, depression, memory problems, muscle disorders.
• Hypersensitivity, such as fever, chills, skin redness, swollen lymph nodes, vasculitis (inflammation of blood vessels).
• Haematological effects, such as anemia, hemolysis (damage to red blood cells), thrombocytopenia (decreased platelet levels).
• Gastrointestinal disorders: nausea, vomiting, constipation, heartburn.
• Hepatotoxicity: liver damage caused by chemicals in drugs.
• Other side effects: headache, palpitations, dry mouth, urinary retention, rheumatism.

If you have chronic liver disease, kidney problems, or a history of seizures, tell your doctor. That way, giving isoniazid will be more careful. In addition, alcohol drinkers, patients over 35 years of age, and pregnant women must receive special supervision.

2. Rifampicin

This drug is a type of antibiotic derived from rifamicin, the same as isoniazid. Rifampicin can kill germs that the drug isoniazid cannot kill.

Rifampicin can kill semi-active bacteria that normally do not react to isoniazid. This drug works by interfering with bacterial enzymes.

Some of the side effects that may arise due to TB treatment with rifampicin are:

• Indigestion, such as heartburn, stomach pain, nausea, vomiting, bloating, anorexia, stomach cramps, diarrhea.
• Central nervous system disorders, such as drowsiness, fatigue, headache, dizziness, confusion, difficulty concentrating, visual disturbances, relaxed muscles
• Hypersensitivity, such as fever, thrush, hemolysis, pruritus, acute renal failure
• Urine changes color due to the red substance in the drug rifampicin
• Menstrual disorders or hemoptysis (coughing up blood)

However, don't worry as these side effects are temporary. Rifampicin is also a risk if consumed by pregnant women because it increases the chance of a birth with spinal problems (spina bifida).

3. Pyrazinamide

The ability of pyrazinamide is to kill bacteria that survive after being resisted by macrophages (the part of white blood cells that first fight bacterial infections in the body). This drug can also work to kill bacteria that are in cells with an acidic pH.

A typical side effect of using this TB drug is an increase in uric acid in the blood (hyperuricemia). That is why patients with pulmonary TB who are prescribed this drug must also routinely control their uric acid levels.

In addition, other possible side effects are that the patient will also experience anorexia, hepatotoxicity, nausea, and vomiting.

4. Ethambutol

Ethambutol is an anti-tuberculosis agent that can inhibit the ability of bacteria to infect, but cannot kill bacteria directly. This drug is given specifically for patients at risk of developing TB drug resistance (resistance). However, if the risk of drug resistance is low, treatment of tuberculosis with ethambutol can be stopped.

The way ethambutol works is bacteriostatic, which means that it inhibits bacterial growth M. tuberculosis who are resistant to the drugs isoniazid and streptomycin. This TB drug also blocks the formation of cell walls by mycolic acid.

Ethambutol is not recommended for tuberculosis in children under 8 years of age because it can cause visual disturbances and side effects are very difficult to control. The side effects of ethambutol that may arise are:

• Visual disturbances
• Color blind
• Visibility narrowing
• Headache
• Nausea and vomiting
• Stomach ache

5. Streptomycin

Streptomycin was the first antibiotic specifically designed to fight tuberculosis-causing bacteria. In the current treatment of tuberculosis, streptomycin is used to prevent the effects of anti-tuberculosis resistance.

The way this TB medicine works is to kill the bacteria that are dividing by inhibiting the process of making bacterial proteins.

The drug for TB streptomycin is given by injection into muscle tissue (intramuscular / IM). Usually this injection type of TB medicine is given if you have experienced TB disease for the second time or the consumption of streptomycin taking medication is no longer effective.

The administration of this TB medicine must pay attention to whether the patient has kidney problems, is pregnant, or has hearing problems. This drug has side effects that disrupt the balance of hearing if taken for more than 3 months.

TB treatment regimen based on patient category

As previously explained, there are 3 categories of TB patients that are determined based on the results of AFB and treatment history. This category further determines what type of treatment regimen is appropriate.

Quoting the TB Facts page, the treatment regimen is a combination of drugs used for TB sufferers with a certain standard code, usually in the form of numbers and capital letters that determine the stage, duration of treatment, and type of drug.

In Indonesia, a combination of anti-tuberculosis drugs can be provided in the form of a kombipak loose drug package or a fixed dose combination antituberculosis drug (OAT-KDT). This kombipak package shows the TB treatment regimen in Indonesia. One kombipak package is intended for one category of patient in one treatment period.

Reporting from the documents of the Indonesian Ministry of Health, the codes used in the tuberculosis treatment regimen are:

Kombipak category I

(Intensive stage / advanced stage)

• 2HRZE / 4H3R3

• 2HRZE / 4HR

• 2HRZE / 6HE

Kombipak category II

(Intensive stage / advanced stage)

• 2HRZES / HRZE / 5H3R3E3

• 2HRZES / HRZE / 5HRE

Kombipak category III

(Intensive stage / advanced stage)

• 2HRZ / 4H3R3

• 2HRZ / 4HR

• 2HRZ / 6HE

With a description that shows:

H = Isoniazid, R = Rifampin, Z = Pyrazinamide, E = Ethambutol, S = Streptomycin

Meanwhile, the numbers in the code indicate the time and frequency. The number on the front shows the duration of consumption, for example at 2HRZES, meaning that it is used for 2 months every day. Meanwhile, the number behind the letters indicates the number of times the drug is used, as in 4H3R3 it means 3 times a week for 4 months.

When consulting, the doctor will usually provide guidance regarding the rules for using this kombipak.

OAT-KDT

Meanwhile, the OAT-KDT or in general terms isFix Dose Combination (FDC) is a mixture of 2-4 anti-tuberculosis drugs that have been put into one tablet.

The use of this drug is very beneficial because it can avoid the risk of prescribing incorrect doses and make it easier for patients to comply with medication regulations. With a smaller number of tablets, it is easier for patients to manage and remember drug use.

There is also a type of insert tuberculosis drug that is given every day for one month if at the end of the intensive stage the category I patient and the re-treatment patient (category II) shows a positive smear.

If you have latent TB, which is a condition in which your body has been infected with bacteria M. tuberculosis, but the bacteria are not actively multiplying, you also need to get TB medicine even if you don't show symptoms of active pulmonary TB. Usually, latent tuberculosis will be treated with a combination of rifampicin and isoniazid drugs for 3 months.

Second-line drug for drug-resistant TB

Today, more and more bacteria are resistant to first-line TB drugs. Resistance can be caused by interrupted treatment, irregular medication schedule, or the nature of bacteria that are resistant to certain types of antibiotics.

This condition is known as MDR TB (Multidrug Resistance). Usually, the bacteria that cause TB are resistant to two types of TB drugs, namely rifampicin and isoniazid.

People with MDR TB will undergo TB treatment using second-line drugs. On the study entitled Tuberculosis Treatment and Drug Regimens, the use of drugs recommended by WHO for drug-resistant tuberculosis patients, namely:

• Pyrazinamide
  
• Amikacin can be replaced with kanamycin
• Ethionamide or prothionamide
• Cycloserine or PAS

Some of the other second-line TB drugs that are also approved by WHO are:

• Capreomycin
• Para-aminosalicylic acid (PAS)
• Ciprofloxacin
• Ofloxacin
• Levofloxacin

Drug-resistant TB patients also have to repeat the TB treatment stages from the beginning so that the total need is longer, namely at least 8-12 months, the worst possibility can be up to 24 months. The side effects of treatment can be even more severe.

Why does TB treatment take so long?

TB-causing bacteria, Mycobacterium tuberculosis (MTB), is a type of bacteria that is resistant to acidic environmental conditions. Once inside the body, these bacteria can "fall asleep" for a long time, aka in a dormant phase. That is, it is in the body, but not reproducing.

Most types of antibiotics, including those used as TB drugs, only function to kill bacteria when they are in the active phase. In fact, in the case of active tuberculosis, there are also bacteria that are in a dormant (inactive) phase.

In the study entitled Why Is Long-Term Therapy Required to Cure Tuberculosis? It is also stated that there are two types of resistance that MTB can have, namely phenotype (influenced by the environment) and genotype (genetic factors).

The study suggests that an abundance of bacteria increases the chance of developing phenotypic drug resistance. As a result, some bacteria can be resistant to several types of antibiotics in the same treatment period. This means that any bacteria that may be resistant need to be treated. That is what causes the duration of TB treatment to take longer.