Multidrug Resistance of Tubercle Bacilli Facts and Implications for National Programmes

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Title: Multidrug Resistance of Tubercle Bacilli
Facts and Implications for National Programmes
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NTI BULLETIN 1993, 29/3A4. 45-47

Reproduced Article

Multidrug Resistance of Tubercle Bacilli*
Facts and Implications for National Programmes

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J. Prignot**
Qeveral recent publications, especially from the US,
Vindicate a rising number of tuberculosis cases caused
by multidrug resistant strains in hospitals, AIDS treatment
centres and prisons and among alcoholics, drug addicts
and the homeless who are very often infected with
HIV1'18.
In many instances there is acquired resistance resulting
from treatment failures or relapses due to disorganized
treatment programmes which do not respect the univer
sally accepted principles of chemotherapy, which involve
taking a correct combination of medications for a suffi
cient period of time: these principles are not followed
by high risk groups which contribute the majority of
tuberculosis cases in industrialized countries. This poor
compliance explains the rise in prevalence of acquired
resistance.
These strains (whose multidrug resistance is ignored or
has only been lately recognized) will cause transmission of
infection, facilitated by the crowded conditions in which
these patients live. In addition these multidrug resistant
cases remain contagious for prolonged periods due to
inefficient chemotherapy and failure to isolate them19. The
rate of transition from infection to disease increases,
especially among patients with immunodeficiency
associated with HIV infection: multidrug resistant bacilli
will be isolated from these patients who have not
previously been treated with chemotherapy. This explains
the rising initial resistance to one or several drugs, mainly
observed in New York for example, where it rose from
10% in 1982-1984 to 23% in 1991 8, though it had steadily
decreased in the US between 1975 and 198220. An in
creased rate of initial resistance had already been observed
in children in Brooklyn in 1981-198421.

With an overall level of resistance (initial and acquired)
of 33%, case fatality of tuberculosis is alarming, reaching
From the IUATLD Newsletter - June 1993
From University of Louvain &. also Editor in Chief. International
Union Against Tuberculosis and Lung Disease. 68 Boulevard Saint
Michel. 75006 Pans.

27% after 9 months’ follow-up in patients in New York
City18. For the US^as a whole, nearly 90% of resistance
appears in HIV positive patients with a case fatality rate of
70-90% four to sixteen weeks after diagnosis19.

This disaster is not surprising considering that resist
ance to isoniazid and rifampicin has reached 19% of the
isolates in New York18, and that 42.6% of the tuberculosis
cases aged 30 to 44 are HIV positive. It is well known that
dual resistance to isoniazid and rifampicin compromises
the results of chemotherapy, and how disappointing the
lack of compliance among high risk groups is: those
leaving hospital in an improved condition often stop
taking the drugs and will be rehospitalized when their
condition worsens again.

Data from well organized national programmes in
Algeria22, Korea23 and South Africa24 provide the direc
tion as to how to address this problem: in these pro
grammes, there has been a decrease in initial and acquired
drug resistance in recent years.
In Korea rates of initial resistance to any single drug
have declined from 30.6% in 1980 to 15% in 1990;
acquired resistance has declined in the same period from
75.4% to 46.8%, multidrug resistance (> 3 drugs) was
found only in 4.7% of newly found cases and 12.9% in old
cases. These results were achieved when the National
Programme recognized the problem, placed high priority
on achieving good results of chemotherapy in the initial
treatment of cases and provided the means to carry it out.
A similar concentration on good results of initial treatment
has achieved the same results in Algeria: the rate of
acquired resistance fell from 81.9% in 1965-67 to 35.7% in
1981-85, and^rimary resistance from 15.0% to 6.3% in the
same period22.
The best policy in regard to drug resistance is to prevent
its development in the first place. This approach has been
clearly demonstrated in Tanzania, where initial resistance
to isoniazid has been stable between 1968, 1978 and 1988,
at between 5 and 8%. Acquired resistance was 41% in
treatment failures and 59% in relapses25.

45

’■ HI

The relation between HIV infection and drug
susceptibility has been studied in Zaire. In Kinshasa, the
rate of initial resistance to H was 19.5%, to H and R 0.9%,
to one drug 22%, to 2 drugs 1.8%, and to 3 drugs 0.9% in
349 samples of consecutive cases"0. In this study there was
no significant difference in resistance between the 218
seronegative and the 131 seropositive patients; these
results indicate that the development of drug resistance in
the United States is unlikely to be directly related to HIV.
These still relatively low rates of initial resistance in Africa
promise excellent treatment results, given that resistance to
H, S and even SH induces only few failures when an initial
four drug regimen. HRSZ or HRSE, is used"7. The success
of such programmes is built upon ensuring strict control of
the use of rifampicin and the provision of an adequate and
complementary retreatment regimen.
In IUATLD programmes, the use of rifampicin is
restricted to the initial phase where drugs are given strictly
supervised; this eliminates the risk of development of
resistance to rifampicin in the continuation phase (often
less well supervised) due to bad compliance.
In future, the highest priority must be to avoid the
development of resistance within National Tuberculosis
Programmes. This can only be achieved by a regular
supply of all the essential drugs28, strict control of the use
of rifampicin, strict observation of its administration and
use in combination tablets and the prohibition of sales of
the drug in the private sector in conjunction with the use of
an adequate retreatment regimen. The very high cure rates
which can be achieved in initial chemotnerapy26-29 are
essential to the prevention and reduction of resistance. In
this regard, the strengthening of National Programmes and
the application of the principles of the IUATLD model in
tuberculosis programmes is of the utmost importance.
An improvement of the situation in the US and its
prevention in other industrialized countries required a
better awareness of the tuberculosis problem in the general
public and among health professionals. Attention to the
basic principles of tuberculosis control and the provision of
adequate material support is needed.
a

The solution to the tuberculosis problem must be
tackled internationally, given the level of migration from
the south to the north and the need for economic assistance
from the north to the south.

Bibliography
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Acknowledgement

10. Edlin BR, Tokars JI, Grieco MH, Crawford JT.
Williams J, Sordillo EM, Ong KR, Kilburn JO.
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among hospitalized patients with the acquired
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I would like to thank Dr. Y.P. Hong, from Korea, for his
pertinent comments which have been integrated into this
article.

II. Nadler JP - Multidrug-resistant tuberculosis. New
Engl. J Med. 1992:327:1172

The global interdependence that has already been
demonstrated in the clinical trials which resulted in
modern chemotherapy is again put to the test with the
problem of multidrug resistance.

46

C,

12. Galai N, Graham N, Chaisson R, Nelson KE, Vlahov
D, Lewis J - Multi-drug-resistant tuberculosis. New
Engl J Med 1992; 327:1172-1173.

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13. Nardell EA, Iseman MD, Kubica G, Riley RL, Stead
WW, Urbach F - Multidrug-resistant tuberculosis.
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22. Boulahbal F, Khaled S, Tazir M - Interet de la
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24. Weyer K, Kleeberg HH - Primary and acquired
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Gangadharam PRJ - Drug resistance in tuberculosis:
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29. Chum HJ - Dix ans de fonctionnement du
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