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Tuberculosis (TB)

Updated : May 9, 2024





Background

Tuberculosis is the second leading cause of infectious disease-related deaths globally with 2 billion people carrying latent TB. In 2021 it had claimed the lives of 1.6 million individuals including 187000 who were coinfected with HIV. TB cases increased by 5% in 2022 to reach 8300 cases with extrapulmonary TB accounting for 21% of reported cases in the US. Screening involves the Mantoux tuberculin skin test, while diagnosis relies on sputum examination for AFB smear and culture.  

TB typically lasts for six months and involves for a multidrug regimen. Pregnant womens, children, and HIV patients or individuals with drug-resistant strains require adjusted plans. Public health measures helps to investigate suspected cases and enforce treatment recommendations. 

  

Epidemiology

TB is a global disease causing 1.4 million deaths in 2020 is notably prevalent in poor countries particularly in South-East Asia and the Western Pacific. The World Health Organization aims to eradicate the disease by 2030 through improved diagnosis, infection control, and new treatment strategies. 

Anatomy

Pathophysiology

Tuberculosis occurs when Mycobacterium tuberculosis bacteria infect the body allowing them to enter the lungs and multiply. Typically, the immune system prevents the infection from spreading but sometimes the bacteria manipulate defenses causing active TB in the lungs.  

M.tuberculosis grows slowly and forms clumps with immune cells developing in lungs, bones, and lymph nodes. If immunity weakens the bacteria multiply rapidly causing symptoms like coughing, chest pain, fatigue, and weight loss. 

Etiology

Tuberculosis grows slowly and requires oxygen for survival its tough outer shell protects it from antibiotics and harsh conditions. The disease spreads through the air when someone coughs, talks, or sneezes affecting the lungs and other body parts. Treatment requires multiple antibiotics to prevent drug-resistant tuberculosis from developing. 

Genetics

Prognostic Factors

TB can cause severe damage to bones, lymph nodes, and brains, ignoring treatment can lead to drug-resistant germs making it harder to cure. HIV patients face additional risks due to weaker immune systems. Early and correct doses of treatment helps in fully eradication of TB and prevent drug resistance. 

Clinical History

Tuberculosis disease (TB) include HIV infection a history of positive purified protein derivative (PPD) test results prior TB treatment, exposure, travel to or emigration from TB-endemic areas, and pulmonary TB. Pulmonary TB may be asymptomatic and detected incidentally on chest radiography while some patients may experience nonspecific symptoms. 

Classic clinical features associated with active pulmonary TB include cough,  fever, hemoptysis from erosion of pulmonary or bronchial arteries due to pleural involvement, fatigue, and chills. Elderly individuals with TB may not exhibit typical signs due to a weaker immune response, and active TB infection may present as non-resolving pneumonitis. 

Physical examination findings may include fullness with decreased fremitus, post-tussive rales, bronchophony, egophony, and whispered pectoriloquy, tubular breath sounds, and amphora. 

Radiographically chest X-ray findings may include patchy or nodular infiltrates, cavity formation, fibrotic scars, and nonspecific lower lobe TB findings. 

Laboratory findings may include normocytic normochromic anemia, hypergammaglobulinemia, hypoalbuminemia, and monocytosis. 

Diagnostic methods include radiographic patterns, gastric content aspiration, tuberculin skin testing (TST), histopathological demonstration of granuloma, culture, and nucleic acid amplification test (NAAT). 

Physical Examination

Physical examinations vary depending on the affected organs. 

For pulmonary TB abnormal breath sounds and rales may indicate lung consolidation. 

Extrapulmonary TB presents with confusion, coma, neurological deficits, lymphadenopathy, chorioretinitis, and cutaneous lesions. 

Lymphadenopathy in TB is painless swelling of one or more lymph nodes usually bilaterally. 

Classic symptoms may be absent especially in high-risk patients and up to 20% of active TB patients may not exhibit symptoms. 

Sputum sampling is crucial when chest radiographic findings suggest TB as up to 20% of patients may not exhibit symptoms. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

  • Pneumonia 
  • Histoplasmosis 
  • Sarcoidosis 
  • Malignancy 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Specialty wise-Pulmonology, Infectious Disease, Internal Medicine, Pediatric 

Tuberculosis (TB) is a disease that requires a specific treatment plan with multiple antibiotics to eliminate bacteria and prevent drug resistance. The usual treatment involves a mix of antibiotics including Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), and Pyrazinamide (PZA). Treatment phases include the intensive phase which uses all four first-line drugs and the continuation phase lasts for 4 to 6 months. 

Directly monitored therapy (DOT) is often used to ensure patients adhere to complete the full treatment plan. A regular check up will improve the patients health conditions in noting symptoms and side effects from treatment. Lab tests involving sputum cultures may occur at predetermined intervals to verify the drug effectiveness and identify drug resistance issues. 

Tackling drug resistance is crucial when treating TB and if resistance is suspected or confirmed the treatment approach must be modified. Multidrug-Resistant TB (MDR-TB) involves resistance to at least two powerful drugs INH and RIF thus requires second-line medications which often carry greater toxicity risks and financial burdens. 

XDR-TB is resistant to INH and RIF as well as certain second-line drugs that necessitating specialized care and expertise. Patient education is essential for proper healing and preventing relapse and drug resistance issues. Preventive therapy with INH medication can lower the chance of developing active TB in some cases. 

 BCG vaccine is used in certain countries to protect children from severe TB forms but does not prevent TB in adult lungs. Supportive care like proper nutrition support and managing side effects that aids the treatment process. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of a non-pharmacological approach for treating Tuberculosis

TB patients require a balanced diet with essential nutrients to strengthen immunity and fight infection. Breathing exercises such as deep breathing and pursed lip techniques can help alleviate respiratory symptoms. Proper hygiene practices and adequate ventilation in living spaces can prevent transmission of TB. 

Psychosocial support such as counseling and support groups can help relieve stress and promote treatment adherence. Education and health promotion are crucial for understanding diagnosis and treatment importance. Home-based care is available for stable TB cases where the infection is drug-sensitive with doctors providing necessary support and monitoring. These measures contribute to better outcomes for TB patients. 

Role of First-line medications in the treatment of Tuberculosis

First-line drugs are crucial for treating tuberculosis (TB) which effectively tackling common strains. Proper use is key for successful treatment. The standard regimen combines several drugs to reduce drug resistance risk. 

Combining first-line drugs shortens treatment duration boosts patient adhesion and reduces relapse or failed treatment.

Group I Medications: 

Isoniazid (INH): 

It helps in treating active tuberculosis by inhibiting mycolic acid synthesis and preventing cell wall formation often combined with other first-line TB medications. 

Rifampicin (RIF): 

It is crucial in TB treatment that inhibits bacterial RNA polymerase and when combined with other first-line drugs that reduces drug resistance risk. 

Pyrazinamide (PZA): 

It is a first-line drug used to target dormant TB bacteria in acidic body tissues, commonly used early in treatment. 

Ethambutol (EMB): 

Ethambutol is used in combination with other drugs to treat pulmonary tuberculosis and prevent Mycobacterium avium complex infections. 

It helps to reduce Mycobacterium tuberculosis infections which can affect the lungs, brain, and spine. 

 

Role of Second line Medications in the treatment of Tuberculosis

Group 2: Injectable Polypeptides and Injectable Aminoglycosides- 

Secondary medications for TB have increased toxicity levels leading to more adverse reactions. Treatments for TB resistant to first-line medication require extended therapy durations and complex dosing schedules with careful tracking of potential side effects crucial. 

Viomycin: 

The current treatment for Mycobacterium tuberculosis infections with viomycin being the first member to be identified and used until capreomycin a less toxic compound, replaced it. 

Capreomycin: 

Capreomycin is an injectable antibiotic used as a second-line treatment for drug-resistant tuberculosis alongside other antituberculosis medications with no reported cases of liver disease. 

  

Injectable Aminoglycosides: 

Kanamycin: 

Kanamycin is an aminoglycoside antibiotic from Streptomyces kanamyceticus that inhibits TB growth by binding to the 70S ribosomal unit thereby impeding protein synthesis. 

Streptomycin: 

Streptomycin is an aminoglycoside antibiotic which is originated from Streptomyces griseus and is now used in multidrug regimens for treating pulmonary tuberculosis. 

Amikacin: 

Amikacin is used for over four decades to treat MDR-TB and is still under debate on the optimal dosage. 

 

Role of third, fourth, and fifth line medications in the treatment of Tuberculosis

Group 3: Injectable and Oral Fluoroquinolones- 

Moxifloxacin: 

Moxifloxacin determine the most suitable dosing for children with rifampin-resistant tuberculosis as there is limited pediatric pharmacokinetic and safety information. 

Ofloxacin: 

Ofloxacin is a fluoroquinolone which is effective against TB but lacks regulatory approval being used as off-label. 

Gatifloxacin: 

Gatifloxacin is a fluoroquinolone antibiotic which is effective in treating bacterial infections and MDR-TB with a recommended doses for pulmonary treatment at 800 mg/day and for meningeal treatment at 1200 mg/day. 

Levofloxacin

This is a crucial drug in addressing latent tuberculosis infection by eliminating dormant TB germs before they cause illness and has shown efficacy against Mycobacterium tuberculosis. 

Group 4 

Para-aminosalicylic Acid (PAS): 

Para-aminosalicylic acid effectively inhibits Mycobacterium tuberculosis growth in both lab and in vivo settings. 

Although its effectiveness is lower than streptomycin the emergence of streptomycin resistant tubercle bacilli after treatment emphasizes the need for precise scheduling and coordination. 

Cycloserine: 

Cycloserine is an oral bacteriostatic second-line agent used to treat tuberculosis specifically targeting drug resistant strains. 

It disrupts TB causing bacteria cell walls leading to their death. It is administered orally to address multidrug resistant cases. 

Ethionamide: 

It is an antibiotic used to treat bacterial infections particularly tuberculosis and should be used alongside other TB medications. 

Prothionamide: 

This is an antimycobacterial agent used in treating tuberculosis typically used in patients with resistance to other drugs in combination with other treatments. 

Thioacetazone: 

Thioacetazone is a tuberculosis medication is not used alone due to its limited efficacy against Mycobacterium tuberculosis. 

Its primary role is to enhance the effectiveness of more potent drugs like isoniazid and rifampicin, preventing resistance development.

Group 5: Medications with Variable but Unproven Efficacy Against TB: 

Clofazimine

This drug is a lipophilic riminophenazine which moved from group 5 to group B in the MDR-TB treatment regimen. 

The pharmacological properties have the tolerability in MDR-TB treatment while focusing its role in tuberculosis treatment and leprosy treatment. 

Linezolid: 

It effectively promotes culture conversion in patients with XDR pulmonary tuberculosis resistant to conventional treatments but the vigilant monitoring for potential adverse events is crucial for safety. 

Amoxicillin/Clavulanic Acid: 

This combination drug is effective against TB causing bacteria, but the research is needed to determine its effectiveness in MDR/XDR TB. 

Imipenem/Cilastatin: 

Cilastatin protects imipenem from degradation and kidney toxicity with a 1:1 ratio. 

Dosing focuses on imipenem dose as cilastatin lacks antibacterial properties limiting cilastatin’s antibacterial properties. 

Clarithromycin: 

Clarithromycin is not a standalone treatment for TB but may combat MDR/XDR TB when paired with other anti-TB drugs. 

Recommended dosage is 500 mg orally every 12 hours. 

 

Use of Intervention with a procedure in treating Tuberculosis

Diagnostic procedures for tuberculosis include sputum collection and analysis which confirms infections and a biopsy, removes body tissue to check for TB outside the lungs. Thoracentesis invoves removal of fluid from the pleural space and abscess to remove infected material from TB abscesses which may develop pus pockets. 

Surgical interventions are necessary for drug-resistant TB which requires the removal of infected lung parts or organs through lobectomy or organ transplantation. Lymph node surgery is a procedure that may be necessary to remove swollen lymph nodes from TB. 

A bronchoscopy involves inserting a thin tube into airways to take lung samples or clear blockages from TB lesions. 

Use of phases in managing Tuberculosis

Screening and Diagnosis: 

Active case finding is crucial for diagnosing individuals with TB symptoms or high risk through community or healthcare facility screenings followed by diagnostic tests like X-rays, sputum smear microscopy, and molecular tests. 

Upon diagnosis the affected individual begins a treatment regimen consisting of isoniazid, rifampin, ethambutol, and pyrazinamide during the initial phase. 

The intensive phase typically lasting a few weeks involves patients receiving daily or weekly drugs to rapidly reduce bacterial load. 

The Continuation Phase involves adjusting drug regimens and monitoring treatment response through clinical or lab evaluations. 

Directly Observed Therapy is to ensure patient adherence and prevent drug resistance. 

Regular monitoring and tracking like clinical enhancements and lab tests is crucial for evaluating effectiveness and addressing adverse reactions. 

Successful treatment prevents relapse or drug-resistant strain development and premature discontinuation can lead to severe consequences. 

Post-treatment monitoring is helpful in cases like potential relapses and prevention that may be offered to individuals who are at high risk of developing active TB disease. 

Medication

 

bedaquiline 

Indicated for pulmonary multidrug resistant tuberculosis (MDR-TB) :


Weeks 1-2: 400 mg orally daily
Weeks 3-24: 200 mg orally 3 times a week, with at least 2 days between doses
the maximum duration of therapy is 24 weeks



pretomanid 

The combination regimen of bedaquiline, pretomanid, and linezolid iIndicated for pulmonary extensively drug resistant (XDR) or unresponsive MDR TB:


Pretomanid: 200 mg orally daily for 26 weeks

Bedaquiline: 400 mg orally daily for 2 weeks, following 200 mg 3 times a week for 24 weeks (a total of 2+24 weeks=26 weeks)

Linezolid 1200 mg orally daily for 26 weeks, if required adjust the dose



linezolid 

Indicated for Tuberculosis drug-resistant :

600

mg

Orally or IV

daily

as part of an appropriate combination regimen including pyridoxine; reduction in dose 300-450 mg once daily or 600 mg for patients who develop toxicity, 3-4 times per week may be used.



moxifloxacin 

400mg orally/intravenous every day



isoniazid 

Latent tuberculosis infection
:


>30kg:300mg orally every day for nine months

3-month regimen
900mg orally weekly once for three months

Active tuberculosis disease
5mg/kg orally/intramuscularly every day.Do not exceed 300mg every day



rifampin 

10mg/kg orally twice a week. Do not exceed 600mg/day



ethambutol 

15 - 25

mg/kg

Tablet

Orally 

once a day

60

days



pyrazinamide 

15 - 30

mg/kg

Orally 

once a day



aminosalicylic acid 

4 g orally 3 times a day
Sprinkle granules over acidic foods or mix them with acidic liquids



rifampin/isoniazid 

The recommended treatment for pulmonary tuberculosis is the administration of rifampin 600 mg/isoniazid 300 mg (equivalent to 2 capsules) orally once a day
This fixed dosage has been proven to be therapeutically effective after the patient has been gradually adjusted to the individual components



suramin 

Administer 10 mg/kg intravenously every five days for a total of 12 injections May be repeated after one month and simultaneously use with tryparsamide



delamanid 

Indicated for Multidrug-Resistant Pulmonary Tuberculosis:

Administer 100mg twice a day for 24 weeks.



dihydrostreptomycin 

It is an antibiotic utilized in the management of infections caused by specific bacteria, including moderate to severe cases of E. coli, tuberculosis, plague, influenza, pneumonia, and various other bacterial infections
The usual recommended dose is 15 mg/kg via IM administration once a day or 25-30 mg/kg two times a week, where the maximum dose should not exceed 1.5 g
It is typically administered once daily through a single intramuscular injection
The total dosage throughout the course of treatment, if there are no alternative options, should not exceed 120 g
For patients aged 60 and above, a reduced dosage is recommended due to an elevated risk of increased toxicity
The decision to conclude therapy with this may be based on various factors, such as the appearance of toxic symptoms, concerns about impending toxicity, the development of bacterial resistance, or the achievement of the desired treatment effect
While the standard duration of tuberculosis treatment with this medication is a minimum of 1 year, termination of therapy may be warranted at any point, as indicated above



Dose Adjustments

Limited data is available

prothionamide 

This medication is used as a second-line treatment for active tuberculosis, a persistent bacterial illness brought on by Mycobacterium tuberculosis, in conjunction with other medications
The maximum amount that can be taken orally is 1g or 1000 mg, and the suggested dose is 15 to 20 mg/kg per day, or roughly 500 to 750 mg



Dose Adjustments

Limited data is available

 

bedaquiline 

Indicated for pulmonary multidrug resistant tuberculosis (MDR-TB) :


Age: ≥ 5 years
Weeks 1-2 (Weight ≥ 30 kg): 400 mg orally daily for 2 weeks
Weeks 3-24 (Weight ≥ 30 kg): 200 mg 3 times a week with at least 2 days between each dose
Weeks 1-2 (Weight 15-<30 kg): 200 mg orally daily 2 weeks
Weeks 3-24 (Weight 15-<30 kg): 100 mg 3 times a week with at least 2 days between each dose



linezolid 

Indicated for Tuberculosis drug-resistant :


600 mg Oral/IV daily as part of an appropriate combination regimen including pyridoxine; reduction in dose to 300 to 450 mg once daily or 600 mg for patients who develop toxicity, 3 to 4 times per week may be used.



isoniazid 

Latent tuberculosis infection
:


10-15mg/kg orally every day

3-month regimen
<2 years: Not recommended
>12 years: 900mg orally weekly once for three months

Active tuberculosis disease
10-15mg/kg orally every day. Do not exceed 300mg every day



rifampin 

10-20mg/kg orally twice a week. Do not exceed 600mg/day



ethambutol 

15 - 25

mg/kg

Tablet

Orally 

once a day



ethambutol 

15 - 25

mg/kg

Tablet

Orally 

once a day



pyrazinamide 

15 - 30

mg/kg

Tablet

Orally 

once a day



aminosalicylic acid 

200-300 mg/kg daily orally divided into 2-4 equal dosages; should not exceed more than 10 g daily
Sprinkle granules over acidic foods or mix them with acidic liquids



dihydrostreptomycin 

It is an antibiotic utilized in the management of infections caused by specific bacteria, including moderate to severe cases of E. coli, tuberculosis, plague, influenza, pneumonia, and various other bacterial infections
The usual recommended dose is 20 to 40 mg/kg via IM administration once a day or 25-30 mg/kg two times a week, where the maximum dose should not exceed 1.5 g



prothionamide 

This active medication is used as a second-line treatment for tuberculosis, a persistent bacterial illness brought on by Mycobacterium tuberculosis, in conjunction with other medications
The maximum amount that can be taken orally is 500 mg, and the suggested dose per day is 15 to 20 mg/kg for 13 to 18-year-olds and 10 mg/kg one time a day for 2 to 12-year-olds



 

ethambutol 

Refer to adult dosing



Media Gallary

Tuberculosis (TB)

Updated : May 9, 2024




Tuberculosis is the second leading cause of infectious disease-related deaths globally with 2 billion people carrying latent TB. In 2021 it had claimed the lives of 1.6 million individuals including 187000 who were coinfected with HIV. TB cases increased by 5% in 2022 to reach 8300 cases with extrapulmonary TB accounting for 21% of reported cases in the US. Screening involves the Mantoux tuberculin skin test, while diagnosis relies on sputum examination for AFB smear and culture.  

TB typically lasts for six months and involves for a multidrug regimen. Pregnant womens, children, and HIV patients or individuals with drug-resistant strains require adjusted plans. Public health measures helps to investigate suspected cases and enforce treatment recommendations. 

  

TB is a global disease causing 1.4 million deaths in 2020 is notably prevalent in poor countries particularly in South-East Asia and the Western Pacific. The World Health Organization aims to eradicate the disease by 2030 through improved diagnosis, infection control, and new treatment strategies. 

Tuberculosis occurs when Mycobacterium tuberculosis bacteria infect the body allowing them to enter the lungs and multiply. Typically, the immune system prevents the infection from spreading but sometimes the bacteria manipulate defenses causing active TB in the lungs.  

M.tuberculosis grows slowly and forms clumps with immune cells developing in lungs, bones, and lymph nodes. If immunity weakens the bacteria multiply rapidly causing symptoms like coughing, chest pain, fatigue, and weight loss. 

Tuberculosis grows slowly and requires oxygen for survival its tough outer shell protects it from antibiotics and harsh conditions. The disease spreads through the air when someone coughs, talks, or sneezes affecting the lungs and other body parts. Treatment requires multiple antibiotics to prevent drug-resistant tuberculosis from developing. 

TB can cause severe damage to bones, lymph nodes, and brains, ignoring treatment can lead to drug-resistant germs making it harder to cure. HIV patients face additional risks due to weaker immune systems.