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

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 Madr

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

H37 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

Resistance to one Drug 181 24.1

Resistance to two Drugs 132 17.6

Resistance to three Drugs 25 3.3

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

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

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

TABLE 6

Three-Drug Resistance

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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Krishnaswamy, K.V and Abdul Rahim, M: Primary Drug Resistance in Pulmonary Tuberculosis Ind

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