tuberculosis%20-%20pulmonary%20(pediatric)
TUBERCULOSIS - PULMONARY (PEDIATRIC)
Tuberculosis (TB) is caused by Mycobacterium tuberculosis, a gram-positive bacteria with slow growth rate that is enhanced by 6-8% carbon dioxide and temperature of 35-40ºC.
It is primarily transmitted through airborne route.
The number of tubercle bacilli expelled in the air by a TB infected person is directly related to their infectiousness.
TB transmission is rare in children <10 years old due to their inability to expectorate sputum and low TB bacilli load in their sputum.
TB infection in children is usually obtained from an infectious adolescent or adult depending on the closeness and length of contact and the index case's severity of lung involvement and infectiousness.

Principles of Therapy

  • Choice of treatment regimen depends on the extent of TB disease, the host, possibility of drug resistance
  • Treatment consists of the intensive phase where actively dividing organisms are efficiently killed & bacillary populations are greatly reduced, & the continuation phase which kills organisms irregularly & slowly, & sterilizes lesions & prevents relapse
    • Intensive phase provides symptom relief, termination of transmission, & prevention of emergence of drug resistance
  • The Rifampicin-based therapy (2HRZE/4HR) is still the recommended approach for drug-susceptible tuberculosis
    • 4-month fluoroquinolone-based therapy is not recommended
  • In the management of drug-susceptible TB, fixed-dose combination tablets are preferred over separate drug formulations
    • In patients with concomitant medical conditions (eg renal dysfunction, liver disease), separate drug formulations are favored in order to adjust the dose for each drug if needed 
  • Infants or children living in places where HIV prevalence or Isoniazid resistance is high, with suspected or confirmed PTB or tuberculous peripheral lymphadenitis, or children with extensive pulmonary disease that live in places with low prevalence of HIV or resistance to Isoniazid should be treated with 2 months of Isoniazid, Rifampin, Pyrazinamide & Ethambutol followed by 4 months of Isoniazid & Rifampin
    • Yields 100% success rate & <2% clinically significant adverse reaction
  • Infants or children with suspected or confirmed PTB or tuberculous peripheral lymphadenitis living in settings with low HIV prevalence or resistance to Isoniazid, & HIV-negative children can be managed with 3-drug regimen consisting of 2 months of Isoniazid, Rifampin & Pyrazinamide followed by 4 months of Isoniazid & Rifampin
  • Intermittent treatment regimen is not recommended in patients with suspected or confirmed PTB or tuberculous peripheral lymphadenitis who live in high HIV prevalence settings
  • An everyday type of dosing is preferred for the treatment of drug-susceptible TB
  • The 3x/week dosing, whether in the intensive phase or in the continuation phase, is no longer recommended due to disease recurrence, drug resistance & treatment failure in comparison to everyday dosing
    • DOT should be implemented if 3x/week dosing is to be used
  • Twice-weekly dosing is no longer recommended because of an increase in the noncompliance rate of PTB patients, applicable in both phases of TB treatment
  • Patients who need to undergo repeat TB treatment should undergo DST
    • If the test reveals absence of resistance to the 1st-line therapy, the same treatment can be prescribed again
    • If the test reveals resistance to Rifampicin, an MDR-TB treatment regimen should be carried out based on the current recommendations of WHO 
  • Dosing frequency: Daily or thrice weekly regimens are recommended
    • 3x/weekly regimen during the continuation phase may be given to HIV-negative patients & those that live in settings with well-established directly-observed therapy (DOT) & in non-HIV prevalent countries
    • Twice-weekly dosing is no longer recommended because of an increase in the noncompliance rate of PTB patients
  • Effectiveness of the treatment depends on patient’s adherence to the regimen
    • Most adult patients are non-infectious after several days to 2 weeks of adequate treatment
  • Adjustment of dosages should be done depending on the patient’s weight, which should be monitored at least once a month

Pharmacotherapy

1st-Line Anti-TB Agents
Isoniazid (H)
  • Indicated for all forms of tuberculosis (TB) caused by organisms that are known or presumed to be susceptible
  • Highly bactericidal against replicating tubercle bacilli
  • Baseline or monthly liver function test is recommended in patients with underlying hepatic disease or on concomitant hepatotoxic drugs (eg other antimycobacterial agents, Paracetamol, alcohol)
Rifampicin (R)
  • Indicated for all forms of TB caused by organisms that are known or presumed to be susceptible & also considered to be an essential component of all short-course regimens
  • Has bactericidal action & a potent sterilizing effect against tubercle bacilli in both cellular & extracellular locations
  • Not to be given with Pyrazinamide for short-course latent TB therapy because of risk for serious liver dysfunction
Pyrazinamide (Z)
  • Indicated for all forms of TB caused by organisms that are known or presumed to be susceptible
  • Weakly bactericidal, but has potent sterilizing activity, particularly in macrophages & in areas of acute inflammation
  • Should not be given with Rifampicin for short-course latent TB therapy because of risk for serious liver dysfunction
Ethambutol (E)
  • Generally used in combination with other anti-TB drugs to prevent or delay the emergence of resistant strains
  • May be omitted from the treatment regimen if patient is clear of drug resistance
  • Bacteriostatic at standard dosages but bactericidal at doses >25 mg/kg
  • Not recommended in patients whose visual acuity & color discrimination cannot be monitored reliably
Streptomycin (S)
  • Used in combination with other antituberculous agents for patients with sputum smear positive patients in relapse, treatment failure or treatment after interruption
Fixed-dose Combination (FDC)
  • Preferred over separate drug formulations for drug-susceptible TB
Multi-Drug Resistant Tuberculosis (MDR TB)
  • Treatment for MDR TB depends on drug sensitivity testing results
  • Perform repeat drug sensitivity tests prior to administration of fluoroquinolones or aminoglycosides
  • A shorter MDR TB treatment regimen (up to 12 month) is recommended for rifampicin-resistant or MDR TB-resistant patients who have not received treatment with any 2nd-line anti-TB agents, & without resistance to fluoroquinolones &/or 2nd-line injectable agents
    • May also add Isoniazid to a conventional MDR TB regimen for patients proven to be without Isoniazid resistance
  • Further studies on the safety & efficacy of below agents other than fluoroquinolones are needed
Aminoglycosides
  • Eg Kanamycin, Amikacin, Capreomycin
  • Belongs to group 2 injectable treatment option for patients with MDR-TB
  • Amikacin is preferred over Kanamycin for intravenous administration
Cycloserine
  • Belongs to 2nd-line oral treatment option for patients with MDR-TB
Ethambutol
  • Recommended 1st-line oral treatment for MDR-TB patients
  • Added to H+R+Z therapy in the presence of monoresistance
Ethionamide
  • Belongs to 2nd-line oral treatment option for patients with MDR-TB
Fluoroquinolones
  • Eg Levofloxacin, Moxifloxacin, Ofloxacin
  • May be given to patients with proven or suspected PTB caused by MDR bacilli in the context of a well-functioning MDR-TB control programme & within an appropriate MDR-TB regimen
  • Belongs to group 3 treatment option for patients with MDR-TB
  • Added to H+R+Z therapy in patients with more extensive & monoresistant TB
Para-aminosalicylic acid
  • Recommended 2nd-line oral treatment for MDR-TB patients
Other Rifamycins
  • Eg Rifabutin, Rifapentine
  • Rifabutin is a treatment option for patients with intolerance to Rifampicin
    • Also used for patients who are undergoing other treatments that have unacceptable interactions with Rifampicin
  • Rifapentine may be used for patients with latent TB infection
    • May be used as a treatment option for patients with drug-resistant TB but further studies are needed to prove its safety & efficacy
Streptomycin (S)
  • Should be used for the treatment of multi-drug resistant TB (MDR-TB) in children with known drug susceptibility
  • Low to moderate evidence of efficacy in children & injection-based treatment regimen limits its use
Extensively Drug-Resistant Tuberculosis (XDR TB)
  • Treatment for XDR TB should be individualized depending on the patient’s drug susceptibility
  • Therapeutic options are the same as with MDR TB patients
Comorbidities
  • All TB patients with HIV should receive antiretroviral treatment (ART) regardless of their CD4 cell count
    • ART should be introduced within the first 8 weeks of TB therapy & within the first 2 weeks of TB therapy if there is significant immunosuppression (eg CD4 cell count <50 cells/mm3)
    • Patients with HIV & TB meningitis should receive vigilant attention since immediate administration of ART is related to more severe adverse reactions
  • All drug-susceptible TB patients with HIV should take ART preferably for 6 months, instead of ≥8 months, during the period of TB treatment
  • The treatment approach for TB meningitis includes the addition of corticosteroid, (eg Prednisolone, Dexamethasone) in a tapering manner for a period of 6-8 weeks
  • Corticosteroid may also be added in the treatment regimen of tuberculous pericarditis

Surgical Intervention

  • May be considered for patients with Rifampicin resistance & MDR TB/XDR TB, in conjunction with pharmacological therapy
  • Elective partial lung resection (lobectomy, wedge resection, pneumonectomy) is preferred
  • Not applicable for patients with HIV, extrapulmonary disease, or for those with XDR TB strains during primary transmission
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