PREVALENCE OF INITIAL DRUG RESISTANCE AMONG PATIENTS ATTENDING THE CLINICS IN MADRAS CITY potx

Ind. J. Tub., 1984, 31, 164

PREVALENCE OF INITIAL DRUG RESISTANCE AMONG PATIENTS ATTENDING

THE CLINICS IN MADRAS CITY

K.V.
KRISHNASWAMI
*, R.
VENKATESAN
**
AND
R.
PARTHASARATHY
***
Summary: Sputum culture of 803 smear positive peases of pulmonary tuberculosis attending for
the first time at the five Chest Clinics located in different parts of Madras, was positive m 750. These
were further subjected to drug sensitivity tests’, 24.1% cultures were resistant to one drug, 17.6% to
two drugs and 3.3% to three drugs, giving a total initial drug resistance of 45%.
Total initial resistance to Isoniazid was 28.9 %, significantly higher than for any other drug.
In the case of Ethambutol and Streptomycin, it was 18.7% and 17.9% respectively. Total initial
resistance to Rifampicin was found to be the lowest as compared to all other drugs.
Introduction
Fairly large proportion of patients attending
for the first time the Chest Clinics in India have
had anti-tuberculosis chemotherapy for some
time though irregularly. The assessment of the
prevalence of Initial Drug Resistance (IDR)
among these patients will be of great value in
their management and also in formulating
general policies of treatment in the Chest

Clinics under the National Tuberculosis Control
Programme.

Material and Methods

Chest symptomatics attending for the first
time at the five Chest Clinics located in different
parts of Madras City, over a period of three
months, from 1st March 1982 till the end of
May 1982, were investigated, irrespective of
whether they had previous chemotherapy or
not.

A preliminary skiagram of the chest was
taken and those with suggestive pulmonary
shadows were subjected to detailed bacterio-
logical investigations commencing with sputum
smears. Two spot and one overnight sputum
specimens were examined for Acid Fast Bacilli
by Ziehl Neelsen procedure. For all the sputum
smear positive cases, culture for M. Tuber-
culosis and drug sensitivity tests were carried
out.

Culture

The technique adopted for culture of M.
Tuberculosis was described by Tuberculosis
Chemotherapy Centre (1959). Two sputum
specimens, one spot and one overnight, were

used.

The following identification tests for M.
Tuberculosis were done:
(a) Niacin production test (Medveczky
1960);
(b) Qualitative test for catalase activity
(Selkon and Mitchison 1959);
(c) Pigmentation and Morphology of growth
after incubation at 37°C for 6 weeks
in the dark and exposed to .light.
Drug Sensitivity Tests

One positive culture from each patient was
subjected to drug sensitivity tests. The drugs
and their concentrations used for the tests were
as follows:

Drug Concentration
1,2,4,16,32, & 64

0,2,1,5,

1,1.4,2,2.8,4,5.6,8,11.2 & 16

5,10,20,28.5,40,57,80, 114

Drug
Streptomycin
Isoniazid

Ethambutol

Ethionamide

Rifampicin

1,2,4,8,16,32,64,128.


A standard (approx. 3 mm) loopful of the
appropriate suspension was inoculated on
Lowenstein-Jensen slopes containing the drug
concentrations and simultaneously on a drug
free slope as control. The standard strain of
H
37
Rv was also set up with each batch of tests.
The results were read at the end of 6 weeks of
incubation at 37°C.

The results for Isoniazid, Ethambutol,
Ethionamide and Rifampicin were expressed
as minimum inhibitory concentration (MIC)
of the drugs inhibiting growth while those of
Streptomycin was expressed as resistance ratio
(RR).

*Formerly Professor of TB & Chest Diseases, Madras Medical College and Director, Institute of TB & Chest
Diseases, Madras.

**Non-medical Tutor in Microbiology ‘“Statistician
PREVALENCE OF INITIAL DRUG RESISTANCE AMONG PATIENTS ATTENDING THE CLINICS IN MADRAS 165

The MIC and RR indicative of Drug Resi-
tance are detailed in Table-I.
TABLE 1
Criteria for Drug Resistance
Results
Seven hundred and fifty specimens of
sputa yielded positive cultures (93%4%) from
among the 803 smear positives investigated.
The culture was negative in 19 smears and
contaminated in 23.

•

TABLE
2
Pattern of Drug Resistance



No. Percentage
Sensitive cases 412 54.9
Resistance to one Drug 181 24.1
Resistance to two Drugs 132 17.6
Resistance to three Drugs 25 3.3
Total 750 99.9
Eleven specimens showed unclassified
mycobacteria.

Analysis of the pattern of Initial Drug
Resistance (IDR) among the 750 positive cultures
(Table 2) shows that 181 (24.1 %) were resistant
to a single drug and 132 (17.6%) were resistant
to two drugs, the difference being statistically
significant (P<0.01).

A small number of patients (3.3%) were

found to be resistant to three drugs, the
differance again being significant (P<0.01) in
comparison to both for single and two drugs.

Of the 750 cases identified as Drug Resistant
cases, a high proportion of 28.9% (Table 3)
were found to be resistant to Isoniazid,
which is significantly higher than the propor-
tions of resistance to any other drug (P<0.01)
in all instances. The proportions of resistance
to Ethambutol and Streptomycin were 18.7%
and 17.9% respectively, the difference between
which was not found to be statistically signifi-
cant. But these proportions were significantly
higher than those for Ethionamide and
Rifampicin. Resistance to Ethionamide and
Rifampicin were found to be of the order of
2.8% and 1.1% respectively with a signifi-
cant difference (P<0.01). IDR for all the four
drugs was found to be significantly higher

than Rifampicin (P<0.01) in all instances).
But still it is to be noted that 8 cases showed
IDR to Rifampicin, a sheet anchor for Short
Course Chemotherapy.

TABLE 3
Drug Resistance to Individual Drugs


Drug

Resistant Cases


No. Percentage

Isoniazid

217 28.9

Ethambutol 140 18.7
Streptomycin 134 17.9
Ethionamide 21 2.8
Rifampicin

8 1.1

Single drug resistance was seen only for
Isoniazid, Ethambutol & Streptomycin (Table 4)
and not for the other two drugs, viz. Ethiona-

mide and Rifampicin. Among those with single
drug resistance, IDR to Isoniazid was signifi-
cantly higher (P<0.01) than that for Etham-
butol and Streptomycin. The difference between
the proportions of cases resistant to Ethambutol
and Streptomycin is not statistically signifi-
cant.

Among the 132 patients who were identified
as being resistant to two drugs initially, the
proportions of resistance to Ethambutol &
INH and Streptomycin & INH were the highest
viz. 40.9% and 34.9% respectively (Table 5).

Name of Drug Minimum Inhi-
bitary concent-
ration
Resistant Ratio
Streptomycin

— 8 & more
Isoniazid

5 & more
Ethambutol

8 & more
Ethionamide

80 & more

Rifampicin

128 & more
166

K.V. KRISHNASWAMI, R. VENKATESAN AND R. PARTHASARATHY



TABLE
4
Single Drug Resistance


Drug

No. Resistant

Percentage

Isoniazid

96

53.0

Ethambutol

45

24.9

Streptomycin

40

22.1

Total

181

100.00

Of the 25 cases who had been found resis-
tant initially to three anti-TB drugs. (Table 6)
8 cases (32 %) were resistant to the three drugs
Streptomycin, Ethambutol and Ethionamide
and 6 cases (24%) to Streptomycin, Isoniazid
and Ethambutol.

Discussion
Initial drug resistance includes (a) naturally
occurring drug resistant mutants, a small insigni-
ficant group, (b) primary drug resistance, i.e.
those infected with drug resistant bacilli, while
not having had the particular drugs themselves
and (c) Acquired resistance in those who have
had chemotherapy knowingly or unknowingly
I do not admit it. Assessment of IDR will

TABLE
5
Two-Drug Resistance


Drugs

No. Resistant

Percentage

Ethambutol & Isoniazid

54

40.9

Streptomycin & Isonizid

46

34.9

Streptomycin & Ethambutol

22

16.7

Streptomycin & Ethionamide

6

4.6

Rifampicin & Isoniazid

4

3.0

Total

132

100.0

TABLE
6
Three-Drug Resistance


Drugs

No. Resistant

Percentage

Streptomycin, Ethambutol & Ethionamide

8

32.0

Streptomycin, Isoniazid & Ethambutol

6

24.0

Isoniazid, Ethambutol & Ethionamide

4

16.0

Streptomycin, Isoniazid & Rifampicin

3

12.0

Streptomycin, Isoniazid & Ethionamide

3

12.0

Ethambutol, Isoniazid & Rifampicin

1

4.0

Total

25

100.0

PREVALENCE OF INITIAL DRUG RESISTANCE AMONG PATIENTS ATTENDING CLINICS IN MADRAS

167


therefore give good indication of the prevalent
practice of chemotherapy and the extent of
patients compliance and consequent possible
reduction in the therapeutic effectiveness of
the drugs routinely used for the treatment of
patients under the National Tuberculosis
Programme. The W:H.O. Expert Committee
on Tuberculosis (IX Report) opined that failure
to respond to the standard regimen of chemo-
therapy because of I.D.R.is more likely to occur
in patients with strains resistant to 2 or all
three drugs in the regimen than those with
resistant to one drug only.

The Indian Council of Medical Research
Second Drug Resistance Investigation (1969)
estimated the prevalence of drug resistance in
patients with Pulmonary Tuberculosis present-
ing for the first time with symptoms at urban
chest clinics in India with or without history
of previous chemotherapy.

Madras was one of the 9 centres participating
in this study. Considering all the centres, 25 %
of the patients had resistance to Isoniazid and
22.9% to Streptomycin; 15.8% were resistant
to both the drugs. In other words, 32 % of the
patients had resistance to either one or both of
these potent drugs. At the Madras Center (The
Institute of Tuberculosis and Chest Diseases),
the IDR findings were 18% for Isoniazid,
15% for Streptomycin and 10% for both and
23% for either or both the drugs in ICMR
study. In the present study it was observed that
28.9% of the patients were resistant to Isonia-
zid, 17.9% to Streptomycin and 7.7% to both
the drugs and 25.7 % for either one or both the
drugs.

Subbammal (1975) reported IDR of 9.1%
for Isoniazid and 4.3 % for both Streptomycin
and Isoniazid from among the cases selected
for chemotherapy trials during 1973-74.
The patients comprised largely of those who

had not had previous chemotherapy and the
prevalence figures were therefore close to those
of Primary Drug Resistance.

In a previous study (Krishnaswamy, and
Abdul Rahim, 1976) prevalence of Primary
Drug Resistance was reported to be 10.6%
for Isoniazid, 9.5% for Streptomycin and
4.7% for both, which proportions were more
or less similar to those reported by the Tuber-
culosis Chemotherapy Centre (Subbammal,
1975).

The salient findings in the present study arc:

1. A sizeable proportion (17.6%) of bacillary
resistance to two drugs was observed among
the freshly reporting bacillary cases;
2. Total resistance to Ethambutol (18.7%)
and Streptomycin (17.9%) was almost
similar.
3. Total Resistance to Rifampicin was 1.1%.
The above findings call for similar studies
in other centres in the country.
Acknowledgements

We thank the Director of Medical Edu-
cation, Tamilnadu, Smt. K. Rukmani, Steno-
typist and the staff of the Laboratory of the
Institute of Tuberculosis and Chest Diseases.

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