Tuberculosis treatment:

general principles and

approach
Lecturer: Ph.D
M.G.Dolynska
 Historical background
 Supposed incurable until XX century
 First approach – sanatorium
movement
 First pathogenically based attempt –
artificial pnemothorax (Forlanini,
1882)
 Streptomycin discovery (Zelman
Waksman, 1943)
 The AIMS of treatment of
tuberculosis are:
 to cure the patient of TB;
 to prevent death from active TB or its
late effects;
 to prevent relapse of TB;
 to decrease transmission of TB to
others;
 to prevent the development of
acquired drug resistance.
 DOTS (Directly observed treatment
short course), Karel Styblo, 1972
The organizational principles of the DOTS
are:
 availability of a decentralized diagnostic
and treatment network based on existing
health facilities;
 good programme management based on
accountability and supervision of health
care workers;
 an evaluation system of case-finding and
cohort analysis of treatment outcomes.
 The five elements of the
expanded DOTS framework
are:
1.Sustained political commitment to increase human and
financial resources and make TB control a nationwide
priority integral to the national health system.
2. Access to quality-assured TB sputum microscopy for case
detection among persons presenting with, or found through
screening to have, symptoms of TB (most importantly,
prolonged cough).
3. Standardized short-course chemotherapy for all cases of TB
under proper case management conditions, including direct
observation of treatment.
4. Uninterrupted supply of quality-assured drugs with reliable
drug procurement and distribution systems.
5. Recording and reporting system enabling outcome
assessment of all patients and assessment of overall
programme performance.
 Dosage and abbreviation of
essential antituberculosis drugs
Drug (abbreviation) Recommended dosage
(dose range) in md/kg
Daily 3 times weekly
Isoniasid (H) 5 10
(4-6) (8-12)
Rifampicin (R) 10 10
(8-12) (8-12)
Pyrasinamide (Z) 25 35
(20-30) (30-40)
Streptomycin (S) 15 15
(12-18) (12-18)
Ethambutol (E) 15 30
(15-20) (20-35)
 Basical treatment regimens
Diagnostic TB patients Treatment regimenI
category Initial phase Continual phase

I New smear-positive Preferred Preferred

patients; new smear- 2 HRZEI 4 HR
negative PTB with 4 (HR)3
extensive parenchymal Optional or Optional
involvement; concomitant 2 (HRZE)3 4 (HR)3
HIV disease or severe or
or
forms of extrapulmonary 6 HEV
2 HRZEIV
TB
II Previously treated sputum Preferred Preferred
smearpositive 2 HRZES / 1 HRZEVI 5 HREVI
PTB: Optional Optional
- relapse; 2(HRZES)3/1HRZE3 5 (HRE)3
- treatment after default
 Basical treatment regimens
(continued)
Diagnostic TB patients Treatment regimenI
category Initial phase Continual phase

III New smear-negative PTB Preferred Preferred

(other than in category I) 2 HRZEVIII 4 HR
and less severe forms of Optional Optional
extra-pulmonary TB 2 (HRZE)3 4 (HR)3
or
6 HE
IV Chronic (still sputum- Specially designed standardized or
positive after supervised individualized regimens
re-treatment); proven or
suspected MDR TB cases.

WHO/CDS/TB/2003.313 Treatment of tuberculosis:guidelines

for national programmes, third edition.
Revision approved by STAG, June 2004
 Criticism concern with the
DOTS strategy
 Clinical
• Lack of smear-negative case detecting
• Lack of case monitoring
 Ethical
• Treatment refusal for certain categories
(especially chronic and smear-negative)
 Epidemiological
• Potential hazard of untreated treated in
improper way patients
 Expanded treatment
conception

 Appropriate antibacterial treatment.

 Hygienic and dietary regimen.
 Pathogenetic measures:
• desintoxication
• hepatotropic therapy
• tissue stimulation
 Collapsotherapy
 Surgical treatment.
For the future, the top priority remains to
administer standardized short
course chemotherapy regimens to all smear
positive cases (new and
retreatment cases). This priority requires the
maximum of effort, time,
drugs and money in a national tuberculosis
programme, without
diverting funds and resources to smear
negative and/or chronic cases.
 Drug resistance
 Primary
Concern with drug-resistant strains
inoculation
 Acquired

Produced by ineffective treatment

 Drug resistance
 Simple drug resistance– resistance
to more than two first line drugs
including isoniasid or rifampicin
 Multidrug-resistance (MDR) –
resistance to more than two first line
drugs including both isoniasid and
rifampicin
 Main resistance types

MDR
MDR

XDR
XDR

Resistance
Resistance

mono
mono poly
poly
 MDR-TB prevalence among new cases and
countries in which at least one XDR-TB case
has been reported

At the end of 2006 year XDR-TB has been detected in 17 countries

 Extensively drug resistance (XDR) –
main definitions

 Firstly has been proposed by US Centers of Disease Control

and Prevention (CDC) in March, 2006: the disease, caused
by MBT, resistant to HR (MDR-TB) and to at least 3
from six classes of antituberculosis second-line drugs
(aminoglycosides, polypeptide, fluoquinolones,
thyamides, cyclocerine, PAS)
 But on WHO meeting devoted to XDR problem (meeting of the
WHO XDR-TB Task Force), on October, 10-11, 2006 difinition
has been changed: the disease, caused by MBT, resistant
to HR (MDR-TB) and to at least some fluoquinolones
and one from 3 injectional antituberculosis drugs :
cyclopentin, kanamycin, amicacin.
 Second line drugs
 Less effective
 More toxic
 Much more expensive
 Classes of second-line
antituberculosis drugs
a Aminoglycosides
When resistance to streptomycin is proved or highly suspected, one of
the other aminoglycosides can be used as a bactericidal agent against
actively multiplying organisms:
• kanamycin, the least expensive, but largely used for indications
other
than tuberculosis in some countries.
• amikacin, as active as kanamycin and better tolerated, but much
more
expensive.
• capreomycin,2 very expensive but very useful in cases with tubercle
bacilli resistant to streptomycin, kanamycin and amikacin.
 Classes of second-line
antituberculosis drugs
b Thioamides
Ethionamide or prothionamide are 2 different presentations of the
same active substance, with bactericidal activity. Prothionamide may
be
better tolerated than ethionamide in some populations.
c Fluoroquinolones
Ofloxacin and ciprofloxacin are two different drugs, but with complete
cross-resistance within the group. These drugs have a low bactericidal
activity, and are useful in association with other drugs. The
pharmacokinetics of ofloxacin are better than the pharmokinetics of
ciprofloxacin. Sparfloxacin should be avoided because of severe
cutaneous side effects (photo-sensitisation). Norfloxacin should not be
used, because it does not give adequate serum levels.
 Classes of second-line
antituberculosis drugs
d Cycloserine (or terizidone)
This is the same bacteriostatic agent, with 2
different formulations. It has
no cross-resistance with other
antituberculosis agents. It might be
valuable to prevent resistance to other
active drugs, but its use is limited
by its high toxicity.
 Classes of second-line
antituberculosis drugs
Para-aminosalicylic acid (PAS)
This is a bacteriostatic agent, valuable for preventing resistance to
isoniazid and streptomycin in the past and to other bactericidal drugs
today.
f Others
Other drugs, sometimes mentioned as second line antituberculosis
drugs, have no place in the treatment of MDR tuberculosis:
• rifampicin derivatives, like rifabutin (21), cannot be used since there
is almost complete cross-resistance between rifabutin and rifampicin
(especially when there is acquired resistance to rifampicin);
• clofazimine has some activity against Mycobacterium leprae and
Mycobacterium ulcerans, but no activity against Mycobacterium
tuberculosis.
 Acceptable regimen for the
treatment of MDR Tuberculosis
It must be made clear to the patient and
staff that meticulously taking the
prescribed reserve regimen is all that
stands between the patient and death.
 Recovery criteria
 Clinicalsymptoms
disappearing
 Morphological changes

resolving
 Sputum conversion (by all

available tests)