TB RX Part 4

TUBERUCULOSIS
PART 4: TREATMENT
Brook Alemayehu, MD
ASTU, School of Health Sciences
TREATMENT: Aims
 To cure the patient of TB.

 To prevent death from active TB or its late
effects.
 To prevent TB relapse or recurrent disease.
 To prevent the development of drug
resistance.
 To decrease TB transmission to others.
TREATMENT
 A suspected TB should be treated with a four drug

combination regimen of isoniazid, rifampin,
pyrinzinamide, and ethambutol
 If multi-drug resistant TB(resistant to INH and

Rifampicin) encountered, therapy should be
prolonged, guided by antibiotic sensitivity
 Directly observed therapys (DOTs) is prefered

strategy for all patients
TREATMENT: Categories
I New sputum smear positive PTB
New patients with severe forms of EPTB
 II Relapse, treatment failure and sputum

smear positive return after default
 III New sputum smear negative

EPTB (less severe forms)
 IV Chronic cases
Multi drug resistant
TREATMENT: New Case
 During the initial phase, there is rapid killing

of TB bacilli.
 Infectious patients become non-infectious within
about 2 weeks.
 Patients improve and symptoms lessen.
 The vast majority of patients with sputum
smear positive PTB become sputum smear-
negative within 2 months.
TREATMENT: New Case
 Directly observed treatment (DOT) is

essential in the initial phase to ensure that
the patient takes every single dose.
 This protects rifampicin against the

development of drug resistance.
TREATMENT: New Case
 Initial phase (2 months)

 The risk of drug resistance is higher during the early
stages of anti-TB drug treatment when there are more
TB bacilli
 RHZE daily for 8 wks followed by RH daily or 2-3 times

wkly for 16 wks
 Regimen may be tailored following results of

susceptibility
TREATMENT: New Case
 Continuation phase (4-6 months)

 At the time of starting the continuation phase
there are low numbers of bacilli and hence less
chance of selecting drug-resistant mutants.
 Thus , fewer drugs are necessary, but they are
needed for a longer time in order to eliminate the
remaining TB bacilli.
 Killing the persisters prevents relapse after
completion of treatment.
TREATMENT: New Case
 Continuation Phase
 DOT is the ideal when the patient receives
rifampicin in the continuation phase.
 If local conditions do not allow DOT, the next best

option is as close supervision as possible,
forexample weekly supervision.
TREATMENT: Modes of Action
 A population of TB bacilli in a TB patient

consists of the following groups:
 metabolically active, continuously growing bacilli
inside cavities;
 bacilli inside cells, e.g. macrophages;
 semidormant bacilli (persisters), which undergo
occasional spurts of metabolic activity;
 dormant bacilli, which fade away and die on their
own.
TREATMENT: Re-treatment
 The initial phase lasts 3 months, with DOT.

 The continuation phase lasts 5 months, with
close supervision.
TREATMENT: Special Groups
 Pregnancy
 Streptomycin during pregnancy can cause permanent
deafness in the baby.
N.B. Do not give streptomycin in pregnancy. Use

ethambutol instead.
 Isoniazid, rifampicin, pyrazinamide and ethambutol are
safe to use.
 Second-line drugs such as fluoroquinolones, ethionamide
and protionamide are teratogenic, and should not be used
 Breastfeeding women
 All anti-TB drugs are compatible with breastfeeding.
 Renal Failure
 Rifampicin, isoniazid and pyrazinamide are safe and
can be given in normal dosages.
 Patients with severe renal failure should receive
pyridoxine with isoniazid to prevent peripheral
neuropathy.
 Renal Failure ctd
 Ethionamide and protionamide are also safe.
 The excretion of streptomycin is renal. The excretion of
ethambutol and thioacetazone is partly renal.
 Avoid streptomycin and ethambutol if there are
alternatives.
▪ Otherwise give in reduced doses at less frequent intervals.
 Do not give thioacetazone. The margin between the
therapeutic window is too narrow.
 The safest regimen to give to patients in renal failure is
2HRZ/4HR.
 Liver diseases
 Most anti-TB drugs can cause liver damage and
therefore care is needed.
▪ Do not give pyrazinamide because this is the most
hepatotoxic anti-TB drug.
 Isoniazid and rifampicin plus one or two non-

hepatotoxic drugs, such as streptomycin and
ethambutol, can be used for a total treatment
duration of eight months.
 Liver diseases ctd

 If the patient has severe liver damage, an alternative
regimen is
▪ Streptomycin plus Isoniazid plus ethambutol in the initial

phase followed by isoniazid and ethambutol in the
continuation phase with a total duration of 12 months.
 Recommended regimens are 2SRHE/6HE or

2SHE/10HE.
TREATMEN: Steroids
* TB meningitis (decreased consciousness, neurological

defects, or spinal block).
* TB pericarditis (with effusion or constriction).
* TB pleural effusion (when large with severe symptoms).
* Hypoadrenalism (TB of adrenal glands).
* TB laryngitis (with life-threatening airway obstruction).
* Severe hypersensitivity reactions to anti-TB drugs.
* Renal tract TB (to prevent ureteric scarring).
* Massive lymph node enlargement with pressure effects.
TREATMENT: Steroids
 Indication Prednisolone treatment
 TB meningitis: 60 mg daily for weeks 1–

4,then
decrease over several weeks
 TB pericarditis : 60 mg daily for weeks 1–4
30 mg daily for weeks 5–8,
then
decrease over several weeks
 TB pleural effusion 30 mg daily for 1–2 weeks
TREATMENT: Steroids
 Is steroid treatment safe in TB/HIV

patients?
 Steroids are immunosuppressants. Steroids may
further depress immunity and increase risk of
opportunistic infections in HIV- positivepatients.
 However, on balance, TB/HIV patients are still

likely to benefit from the use of steroids for the
above indications.
TREATMENT: Monitoring
 When to monitor 8-month treatment 6-month

treatment
regimen
 At time of diagnosis sputum smear sputum smear
 At end of initial phase sputum smear sputum smear
 In continuation phase sputum smear sputum smear
(month 5) (month 5)
 During last month of sputum smear sputum smear
Treatment (month 8) (month 6)
TREATMENT: Side Effects
 Reaction Drug
 severe rash, agranulocytosis thioacetazone
 hearing loss or disturbed streptomycin
balance
 visual disturbance (poor vision ethambutol
and colour perception)
 renal failure, shock, or rifampicin
 thrombocytopenia
 Hepatitis pyrazinamide
TREATMENT: MDR TB
 Epidemiology: Worldwide
Global
 Half a million cases of MDR-TB emerge every year,
 only 3% get treatment globally
 110,000 die annually
TREATMENT: MDR TB
 Epidemiology: Ethiopia
 National
▪ Ethiopia is one of the 27 high burden M(X)DR-TB
countries ranking 15th
▪ >5000 estimated MDR-TB patients annually.
 Prevalence
▪ Drug resistance type New case Re-treatment
▪ MDR 1.6% 11.8%
▪ Isoniazid Mono resistance 2% 5.3%
▪ Rifampicin Mono resistance 1% 1.3%
TREATMENT: MDR TB
 Risk factors
 Failure of re-treatment Category II regimen and
chronic TB cases
 Exposure to a known MDR case
 Relapse and return after default
 HIV co-infection
 Patients who remain sputum smear positive at 2-3
month
TREATMENT: MDR TB
 Risk factors ctd

 Residence in area with documented high
transmission of MDR-TB
 History of using anti-TB drugs of unknown or poor
quality
 Co-morbid condition associated with
malabsorption or rapid transit diarrhoea
TREATMENT: MDR TB
 Categories of Resistance
Mono-resistance
resistance to one anti-tuberculosis drug.
Poly-resistance
resistance to more than one anti-tuberculosis
drug, other than both isoniazid and rifampicin
TREATMENT: MDR TB
 Categories of Resistance ctd

Multidrug-resistance
resistance to at least isoniazid and rifampicin.
Extensive drug-resistance
Multidrug-resistance plus
resistance to any fluoroquinolone, and at least
one of three injectablesecond-line drugs
(capreomycin, kanamycin and amikacin)
TREATMENT: MDR TB
 Diagnosis
 Drug Resistant TB is confirmed through drug

sensitivity test (DST)
TREATMENT: MDR TB
 Principles of Management of MDR TB

 Early diagnosis and management of DR-TB
 Prompt treatment with adequate regimen
 Patient support
 Strong infection control measures
 Close contacts of M(X)DR-TB patients should have
careful clinical follow-up for a period of at least
two years
THANK YOU!

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TUBERUCULOSIS

 To cure the patient of TB.

 A suspected TB should be treated with a four drug

 If multi-drug resistant TB(resistant to INH and

 Directly observed therapys (DOTs) is prefered

 II Relapse, treatment failure and sputum

 III New sputum smear negative

 During the initial phase, there is rapid killing

 Directly observed treatment (DOT) is

 This protects rifampicin against the

 Initial phase (2 months)

 RHZE daily for 8 wks followed by RH daily or 2-3 times

 Regimen may be tailored following results of

 Continuation phase (4-6 months)

 If local conditions do not allow DOT, the next best

 A population of TB bacilli in a TB patient

 The initial phase lasts 3 months, with DOT.

N.B. Do not give streptomycin in pregnancy. Use

 Isoniazid and rifampicin plus one or two non-

 Liver diseases ctd

▪ Streptomycin plus Isoniazid plus ethambutol in the initial

 Recommended regimens are 2SRHE/6HE or

* TB meningitis (decreased consciousness, neurological

 Indication Prednisolone treatment

 TB meningitis: 60 mg daily for weeks 1–

 Is steroid treatment safe in TB/HIV

 However, on balance, TB/HIV patients are still

 When to monitor 8-month treatment 6-month

 Risk factors ctd

 Categories of Resistance ctd

 Drug Resistant TB is confirmed through drug

 Principles of Management of MDR TB

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