Chemotherapy of Pulmonary Tuberculosis in Young Adults
Authors: M. Daniels, A. B. Hill
Journal: BMJ (1952)

PREVENTION OF STREPTOMYCIN RESISTANCE MtfJALof cases becoming tubercle-negative and to the x-ray changes.Similar numbers in the three groups became suitable for collapse therapy.Results of streptomycin-sensitivity tests, however, show clear differences between the groups; in the first three months very few of the cases on 10 or 20 g. of P.A.S. developed drug-resistant strains, whereas of those on only 5 g. one in three had resistant strains in the third month.Subsequently the percentages of resistant strains' rose in both the groups on small doses of P.A.S., and remained low only in the group on 20 g. daily: in the fourth month the proportion of resistant cases was 47% in the SP 5 group, 43% in the SP 10, and only 15% in the SP 20; these differ- ences persisted in subsequent months.There is no doubt that the dose of 20 g. is much more effective in preventing emergence of streptomycin resistance than are doses of 10 or 5 g., and that in adults the higher dose should be administered if it is tolerated.The clinical significance of these results is discussed elsewhere in this issue by Daniels and Bradford Hill (1952).Other methods of preventing emergence of streptomycin resistance have not been investigated here, though one at least has been reported to be most effective.Administration of streptomycin every third or fourth day reduces the risk of emergence of streptomycin resistance and, it is claimed, without loss of clinical effect; combination of this regime with daily administration of P.A.S. reduces the risk even further (Veterans Administration, 1949-50).Summary A series of 115 patients with acute progressive bi- lateral pulmonary tuberculosis unsuitable for collapse therapy were studied in a clinical trial of streptomycin and P.A.S.All were treated for three months with I g. of streptomycin daily; in addition, 42 were given 20 g. of P.A.S. daily (SP 20), 39 had 10 g. (SP 10), and 34 had 5 g.(SP 5).Patients were assigned to one or another treatment group by random selection.Gastro-intestinal disturbance was infrequent (12-15 %) and mild in the two groups on lower doses of P.A.S.; in the group receiving 20 g. of P.A.S. the incidence was 52%.The radiological assessment of change at the end of six months shows no difference between the three groups.The proportion showing improvement was 87-88 %.No differences were found between the groups in respect of changes in temperature, sedimentation rate, general condition, or bacterial content of sputum.Analysis of results of streptomycin-sensitivity tests show significant differences between the groups.In the third month 32% of SP 5 cases had resistant strains, against 8% in the SP 10 group and 4% in the SP 20 group.Subsequently the figures rise in both groups on lower doses, and remain very low in the SP 20 group.In the fourth month the proportion of resistant cases was 47% in the SP 5 group, 43% in the SP 10, and 15 % in the SP 20.In the sixth month the corresponding figures were 36%, 30%, and 7%.Reversion to sensitivity was observed frequently, in all three groups, in cases with moderately resistant strains.