By
INTRODUCTION
Prior to 1950s the mainstay of management was
bedrest, fresh air, sunshine (where available)
and in suitable cases, surgical intervention
resection of tuberculosis lesions
more commonly the active management depended
on collapse therapy, collapsed therapy rested
diseased lung and might take the form of artificial
pneumothorax, pneumoperitoneum. Collapse of
the lung by pleural plombage in which the pleural
& hence the underlying lung, were compressed by
implanted material (e.g lucile balls or mineral oil).
Drugs
Schatz and Waksman in 1944 discovered
streptomycin, which heralded a new era of
tuberculosis chemotherapeutics
PAS by Lehmann, followed by INH in 1952
Controlled Clinical Trials on Early Drugs
British Medical research Council - World 1st
control clinical trial
Treated Group
Control Group
Drugs (Continued)
Development of PAS and Isoniazid
Study
INH
PZA
Actively multiplying
extracellular bacilli
Inadequate Rx:
Treatment
Failure
Slowly multiplying
intracellular and in
closed caseous
lession
Adequate Rx:
bactericidal
action
Adequate Rx:
sterilizing action
Elimination
of
extracellula
r
Elimination of
persisters
Lasting cure of
tuberculosis
Inadequate Rx:
Late growth of
persisters
Relapse
Aminoglycoside
capreomycin
kanamycin
viomycin
Fluoroquinolone
Ciprofloxacin
Ofloxacin
Newer Drugs
Rifambutin
Rifapentin
Initial
Phase
Continuation
Phase
No. of
Subjects
Follow-up Relapse
(Months) %
2SHRZ
2SHRZ
4HRZ
4HR
84
80
6
6
0
1
2SHRZ
1SHRZ
2HRZ
4H3R3Z3
5H3R3
4H3R3
97
94
109
24
24
24
1
1
1
4HR
229
24
2SHRZ
4TH
89
4TH
105
24
4H2R2
4H2R2
56
116
24
24
2
3
2SHRZ
2HRZ
EXTRAPULMONARY TUBERCULOSIS
Standard 9-month
chemotherapy or 6month chemotherapy
Standard 6 or 9-month
chemotherapy plus
prednisolone 40mg OD for
6 months
Steroid to prevent
ureteric stricture
Standard 6-month chemotheray
Miliary Tuberculosis
Standard 6-month chemotherapy
Streptomycin is ototoxic
to the fetus and is
contraindicated
Because of difficulties
in monitorin for ocular
toxicity, Ethambutol is
best avoided
Natural mutations
Resistant mutants
(2)
Transmission
in droplets
Further transmission
HIV infection
Inadequate infection control
Diagnostic delay
Summary
The worst possible scenerio, one in which
tubercle bacilli become increasingly resistant
to multiple drugs resulting effectively in a
return to the prechemotherapy era of
tuberculosis with 50-80% mortality rates, will
only be avoided if the long-established
principles of treating tuberculosis are rigidly
observed. At present, this means considering
the need for DOT for every patient