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March 1988, Volume 38, Issue 3

Original Article

PRIMARY DRUG RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS TO ANTITUBERCULOSIS DRUGS

Mohammad Iqbal Safi  ( PMRC Research Centre, Khyber Medical College, Peshawar. )
Salar Zai  ( PMRC Research Centre, Khyber Medical College, Peshawar. )

Abstract

Thirty two positive sputa from 104 untreated cases of pulmonary tuberculosis, were tested for sensi­tivities against antituberculosis drugs. Twenty four were positive on direct smear as well as culture while 8 were only culture positive. Nine (28%) were resistant to Isoniazid, 3 (9.4%) to Streptomycin and 2 (6.3%) were resistant to both the drugs. All the 32 were sensitive to Rifampicin and Ethambutol(JPMA 38: 73 , 1988).

INTRODUCTION

Tuberculosis is a major health problem of developing countries includbg Pakistan. Consi­derable advancement has been achieved in the management of the disease with the introduction of new more potent and less toxic drugs, but the problem of drug resistance has also increased. In the economically advanced countries primary drug resistance has been reported in 3-5% of cases1. From Hong Kong, a prevalence rate of 15% of primary thug resistance has been reported2, in Latin America, it is as high as 22%. From Peru primary resistance to INH of 7.3%, Rifampicin 1.5%, Streptomycin 73% and to combination of Rifampicin, NH and Streptomycin of 1.5% has been reported3. Primary resistance in Korea was found to be 3 1%4 while in Haiti 32% of patients had resistant organisms to one or two antituber­culosis drugs5. Haphazard use of antituberculosis thugs is common in Pakistan. Combination of Strep­tomycin and Penicillin is also in use for common infections. This study was undertaken at PMRC Research Centre at Khyber Medical College to document the prevalence of primary drug resistance to the commonly used antituberculosis drugs.

MATERIAL AND METHODS

From 3890 patients who attended the district Tuberculosis control centre during the period May 1981 to August 1983, 104 new patients were selected for the study. The criteria for selection were:
1. Patient with no history of previous antitu­berculosis treatment, or combination of Streptomycin, Penicillin (combiotic) for more than 5 days.
2. Chest X-ray showing a cavity or infiltra­tions in the upper lobe or upper segment of lower lobe or any other shadow consis­tent with the disease.
An early morning specimen of 10—20 ml sputum was collected from each patient. In patients who could not produce the required quantity, 24 hours collection of sputum was carried out. The sputum sample was transferred to a centrifuge tube with a screw cap. An equal volume of 1-cystemine sodium hydroxide was added, mixed well and the mixture allowed to stand for 30 minutes. Distilled water was then added and the mixture centrifuged at 3000 rpm for 30 minutes. A smear was prepared from the sediment and stained for acid fast bacilli. A portion of the sediment was also inocu­lated on to two tubes of Lowen Stein Jenson (U) slants. A third tube of Li. containing sodium salicylate was also inoculated for species identifi­cation. These L.J. Slants were incubated at 37°C and examined for growth at weekly intervals for maximum of 8 weeks. Colonies from positive cultures were trans ferred to a sterile tube containing 6-8 glass beads and 3 ml normal saline. The mixture was homoge­nised and then shaken for 10-15 minutes. Serial 10 fold dilutions were then prepared in sterile distilled water. These were inoculated on to drug containing media and incubated at 37°C for one week to study drug sensitivity patterns.

RESULTS

Of the 104 sputum samples studied, 32 (30.8%) gave a positive culture for mycobac­terium tuberculosis (human). Of these eight were smear negative (Table).

The sensitivity pattern is thown in the table. ALl were sensitive to rifampicin and ethambutol. Three (9.4%) were resistant to streptomycin while 9(28%) exhibited resistance to INH. Two (6.3%) were resistant to the combina­tion of INH Strep tomycin.

DISCUSSION

This study gives two important informa­tions regarding tuberculosis in the area. Firstly, during the 18 months period of the study, of the 3890 patients registered at the T.B. Control Centre, only 104 (2.67%) were new cases. The rest were patients who had been visiting various clinics, practitioners and hospitals and had been taking irregular treatment. This shows that although case finding may be an important problem in the management of the disease, case holding is a greater problem. Patient compliance and unifor­mity of treatment are aspects of the T.B. problem which require special consideration. Secondly, the initial drug resistance to commonly used antituberculosis drugs i.e., Strep­tomycin and INH is quite high. Previous studies in Pakistan showed a high resistance to S.M. , INH and PAS in treated cases1. In the study of Jafri, 2 drug resistance in untreated cases was not signi­ficant and this author concluded that the danger of spread of resistant bacffli in a population is more apparent than real. Snider et al3 from USA have also reported that despite the widespread use of antituberculosis drugs, primary resistance is not increasing. This is attributed to the low patho­genicity of the drug resistant tubercle bacilli as compared to drug sensitive mycobacteria. Our study shows a high prevalence of primary drug resistance but since previous figures from this area are not available, we cannot comment whether any increase has occurred. Our results are comparable to those of Latin American and South East Asian countries3-6. The obvious explanation for the very high primary drug resistance prevalence in our population is due to irregular and inadequate use of drugs and low patient compliance.

ACKNOWLEDGEMENT

The authors are grateful to Pakistan Medical Research Council for financing the study, to staff of PMRC Research Centre, Khyber Medi­cal College for laboratory and statistical help and help in the preparation of manuscript, to Wahid Gul BCG, D.T.O. Peshawar for helping in interviewing patients.

REFERENCES

1. Gilani, S. and Khan, A.M. Drug sensitivity pattern of mycobacterium tuberculosis. Pakistan J. Med. Res., 1967 :6: 93.
2. Jafri, A.H. Evaluation of resistance of tubercie bacilli to various chemotherapeutic agents. Pakistan J. Med. Res., 1969; 8 : 67.
3. Snider, E., Kelly, GD., Thompson, NJ., Kil­burn, J.O. and Good, R.C. Infectiousness and pathogencity of mycobacterium tuberculosis. Am.Rev.Resp.Dis., 1981;123 :254
4. Toman, K. Tuberculosis chemotherapy; questions and answers.Geneva, WHO, l979;p.87.
5. Committee on Bacteriology and Immunology Bulletin of International Union against Tuber­culosis,1986;6l :56.
6. Lin, H.T. The tuberculosis problem and its control in East Asia and South Pacific area, Bulletin of International Union against Tuber­culosis, I986;6 : 28.
7. Pitchenick, K. A., Russell, B.W., Cleary, T., Pejovic, I., Cole, C., and Snider, D. E. Jr. The prevalence of tuberculosis and drug resistance among Haitians. N. Engi. J. Med., 1982;307 :162.

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