Severe Tuberculosis Disease

Indications

• Includes more serious pulmonary TB, such as smear-positive TB, cavitatory pulmonary TB, bronchopneumonic TB, extensive (multiple lobes involved) pulmonary TB disease, and tuberculous empyema.
• Includes all HIV/TB co-infected cases.
• Includes extrapulmonary TB, e.g. spinal, osteo-articular or abdominal TB.

However:

• Exclude TB meningitis and miliary TB.

Dosing:

• Weigh at each visit and adjust treatment doses to body weight. If calculating dosages, rather give ½ tablet more than ½ tablet less.
• Keep strictly to the correct dose and the duration of treatment.
• The patient should be weighed regularly and the dose adjusted according to the current weight.

Children up to 8 years of age: Intensive phase:

Standard dose 4-drug therapy daily (RHZE) for 2 months.

Follow with: Continuation phase:

Standard dose 2-drug therapy daily (Isoniazid + Rifampicin) for 4 to 7 months.

Dosing recommendations for dispersible combinations tablets:

Pretreatment body weight	2 months intensive phase given daily		4–7 *** months continuation phase given daily
	RHZ	E	RH
	75/50/150 mg dispersible tablet (scored) OR 75/50/150 mg per 4 mL solution*	400 mg tablet OR 400 mg/8 mL solution**	75/50 mg dispersible tablet (scored) OR 75/50 mg per 4 mL solution*
2–2.9 kg	½ tablet or 2 mL	1 mL	½ tablet or 2 mL
3–3.9 kg	¾ tablet or 3 mL	1.5 mL	¾ tablet or 3 mL
4–7.9 kg	1 tablet or 4 mL	2.5 mL	1 tablet or 4 mL
8–11.9 kg	2 tablets or 8 mL	½ tablet or 4 mL	2 tablets or 8 mL
12– 15.9 kg	3 tablets or 12 mL	¾ tablet or 6 mL	3 tablets or 12 mL
16–24.9 kg	4 tablets or 16 mL	1 tablet or 8 mL	4 tablets or 16 mL

Note:

Children should be taught and encouraged to swallow whole tablets or, if required, fractions of tablets so as to avoid large volumes of liquid medication.

*If oral suspension required, for each dose, disperse 1 x RHZ 75/50/150 mg or 1 x RH 75/50 mg tablet in 4 mL of water, administer required dose, discard unused suspension.

**If oral suspension required, for each dose, crush 1 x ethambutol 400 mg tablet to a fine powder, disperse in 8 mL of water to prepare a concentration of 400 mg/8 mL (50 mg/mL), administer required dose as indicated in above chart, discard unused suspension.

***Continuation phase may be prolonged to 7 months in slow responders and children with HIV.

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	Intensive phase 2 months				Continuation phase at least 4 months (up to 7 months ***)
Weight	RH	PZA Give one of the following:		EMB	RH
	60/60	150 mg* OR 150 mg/3 mL	500 mg	400 mg tablet OR 400 mg/8 mL** solution	60/60
2–2.9 kg	½ tablet	1.5 mL	Expert advice on dose	1 mL	½ tablet
3–3.9 kg	¾ tablet	2.5 mL	¼ tablet	1.5 mL	¾ tablet
4–5.9 kg	1 tablet	3 mL	¼ tablet	2 mL	1 tablet
6–7.9 kg	1½ tablets		½ tablet	3 mL	1½ tablets
8–11.9 kg	2 tablets		½ tablet	½ tablet	2 tablets
12–14.9 kg	3 tablets		1 tablet	¾ tablet	3 tablets
15–19.9 kg	3½ tablets		1 tablet	1 tablet	3½ tablets
20–24.9 kg	4½ tablets		1½ tablet	1 tablet	4½ tablets
25–29.9 kg	5 tablets		2 tablets	1½ tablets	5 tablets

Notes:
*For each dose, dissolve 150 mg dispersible (1 tablet) in 3 mL of water to prepare a concentration of 50 mg/mL (150 mg/3 mL).

**For each dose, crush 400 mg (1 tablet) to a fine powder and dissolve in 8 mL of water to prepare a concentration of 400 mg/8 mL. Discard unused solution.

***Continuation phase may be prolonged to 7 months in slow responders and children with HIV.

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AND

• Pyridoxine, oral, daily for 6 months if HIV-infected, malnourished, or with existing neuropathy:
  • Child < 5 years: 12.5 mg.
  • Child ≥ 5 years: 25 mg.

Children > 8 years and adolescent:

Pretreatment body weight	2 months intensive phase given daily	4 months continuation phase given daily
	RHZE (150, 75, 400, 275)	RH (150, 75)	RH (300, 150)
25–37.9 kg	2 tablets	2 tablets
38–54.9 kg	3 tablets	3 tablets
55–70.9 kg	4 tablets		2 tablets
> 71 kg	5 tablets		2 tablets

AND

Pyridoxine, oral, daily for 6 months if HIV-infected, malnourished, or with existing neuropathy:

• Child < 5 years: 12.5 mg.
• Child ≥ 5 years: 25 mg.

Adjust treatment dosages to body weight. If calculating dosages, rather give ½ tablet more than ½ tablet less.

REFERRAL

• Poor response to standard TB treatment.
• Failure to exclude MDR-TB.
• Adverse drug reactions (ADR) requiring single drug combinations.
• MDR or MDR-TB contact.

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Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition

Chapter 10: Tuberculosis, 10.2 Tuberculosis, Pulmonary In Children,  10.2.2 Severe Tuberculosis Disease