Drug resistance in patients with pulmonary tuberculosis O.T. Cheung, MB,
DPH
Summary: A review of the records of 984 patients admitted hospital from 1970 through 1973 with bacteriologically proven pulmonary tuberculosis showed bacterial resistance to one or more antituberculosis drugs in 103 (10.5%). Among the patients who had had previous drug treatment for tuberculosis the prevalence of drug resistance was 20% in the Canadian-born patients and 694% in the recent immigrants. Among the patients who had had no previous drug treatment the prevalence of drug resistance (primary resistance) was 2.7% in Canadian-born patients but 11.4% in recent immigrants. Because of the higher prevalence of drug resistance among recent immigrants and the finding in recent years that increasingly more tuberculosis patients in Ontario are recent immigrants, drug resistance in this group is likely to assume even more importance in the future.
to
Resume: La resistance aux medicaments chez des malades souffrant de tuberculose pulmonaire Une revue des dossiers de 984 malades hospitalises entre 1970 et 1973 pour une tuberculose pulmonaire demontree par des examens bacteriologiques a revele une resistance bacterienne a au moins un medicament antituberculeux chez 103 d'entre eux (10.5%). Parmi les malades traites auparavant par des antituberculeux, la frequence de la resistance medicamenteuse etait de 20% chez les personnes nees au Canada et de 69.4% chez les immigrants recemment entres au pays. Parmi les malades qui n'avaient Jamais auparavant recu de traitement antituberculeux, la prevalence de la resistance medicamenteuse (resistance primaire) etait de 2.7% chez les Canadiens de naissance mais de 11.4% chez les immigrants recents. Etant donne la plus grande prevalence de la resistance medicamenteuse parmi les immigrants recents, ainsi que le fait recemment etabli que de plus en plus des malades souffrant de tuberculose pulmonaire en Ontario sont des immigrants recents, il est probable que la prevalence de la resistance aux medicaments dans ce dernier groupe sera d'une importance croissante a I'avenir. From Toronto Hospital, Weston, Ont. Presented at the International Conference on Lung Diseases, Montreal, May 18 to 21, 1975 Reprint requests to: Dr. O.T. Cheung, Toronto Hospital, Weston, ON M9N 3M6
848 CMA JOURNAL/NOVEMBER 8, 1975/VOL. 113
Jessamine, Eidus and Narasimhan1 recently reported that
the prevalence of primary drug resistance in tuberculosis is noticeably high among recent immigrants to Canada. To confirm this finding I reviewed the records of patients with pulmonary tuberculosis admitted to Toronto Hospital, Weston during a 4-year period. Methods
The records of all patients with bacteriologically proven pulmonary tuberculosis, either those with newly diagnosed disease or those requiring retreatment, admitted to Toronto Hospital from 1970 through 1973 were reviewed; the data of those whose sputum was positive for drug-resistant My¬ cobacterium tuberculosis var. hominis were selected for analysis. Much of the bacteriologic work was performed by the laboratory services branch of the Ontario Ministry of Health. The patients were divided into three groups: (a) Cana¬ dian-born patients, (b) foreign-born patients who had lived in Canada for more than 5 years before admission to hos¬ pital and (c) foreign-born patients who had lived in Canada for 5 years or less before admission to hospital. For the purpose of this report the third group is designated as recent immigrants. Results
Of 984 patients with proven pulmonary tuberculosis ad¬ mitted to hospital the tubercle bacilli were resistant to anti¬ an overall prevalence of tuberculosis drugs in 103 10.5%. Of the 103 patients 63 were male and 40 were female. Twelve patients were 1 to 19 years old, 43 were 20 to 39 years, 25 were 40 to 59 years and 23 were 60 years or more. Twenty-six patients were Canadian-born and 77 26 from were foreign-born; 50 were recent immigrants Asia, 20 from continental Europe, 2 from South America, 1 from Africa and 1 from the British Isles. The findings on drug resistance are summarized in Table I. Among 153 patients who had had previous drug treat¬ ment for tuberculosis the prevalence of drug resistance was 35.3%. However, within this group the prevalence was 20% among 80 Canadian-born patients but 69.4% among 36 recent immigrants. Among 831 patients who had had no previous drug .
.
treatment for tuberculosis the overall prevalence of drug resistance (primary drug resistance) was 5.9%. The prevalence was only 2.7% among 372 Canadian-born patients but 11.4% among 219 recent immigrants. Thus, primary drug resistance was four times as common in recent immigrants as in Canadian-born patients. Of the 153 patients who had had previous drug treatment for tuberculosis the prevalence of resistance to isoniazid, streptomycin and para-aminosalicylic acid was high. Resistance to ethambutol was infrequent and that to rifampin, nonexistent. Of the other 831 patients the prevalence of primary drug resistance was low among the 372 Canadian-born patients, but relatively high among the 219 recent immigrants. There was no resistance to ethambutol or rifampin. The patients were treated with various combinations of antituberculosis drugs, including ethambutol in 78 patients and rifampin in 68 patients. The results of treatment were good: in 92% the sputum became negative within 6 months. Discussion In a nationwide survey on primary drug resistance in tuberculosis in Canada, carried out in 1963-64, Armstrong2 found that the tubercle bacilli of 4.8% of the patients were resistant to one or more antituberculosis drugs. In the present study, confined to patients in the Toronto area, the overall prevalence of primary drug resistance was 5.9%, being higher in recent immigrants (11.4%) than in Canadian-born patients (2.7%). Although Armstrong did not examine his data according to the country of origin of the patients or duration of residence in Canada when the diagnosis was made, it is probable that he surveyed relatively fewer recent immigrants than I did. The slightly higher rate of 5.9% in my study probably reflects this difference in the composition of the groups surveyed. It is probably safe to conclude that primary drug resistance in tuberculosis in Canada has not increased appreciably. The results of the present study have confirmed the
finding of Jessamine and colleagues1 that the prevalence of primary drug resistance is high among recent immigrants. Among the 41 immigrants they examined, resistance to one or more antituberculosis drugs was found in 19.5%. The prevalence of drug resistance among recent immigrants in my study was 11.4% - four times as high as the prevalence among Canadian-born patients. Although the number of instances of drug resistance noted in the 4-year period reviewed was not large, it is important that about one half of all instances were in recent immigrants. In a study on the influence of immigration on tuberculosis in Ontario in 1961-7 1 Ashley, Anderson and le Riche3 noted that increasingly more of the patients with tuberculosis in Ontario were recent immigrants. Drug resistance among recent immigrants is likely to assume more importance in the future. In view of the findings of this study, I suggest that when a recent immigrant is found to have active pulmonary tuberculosis, and if treatment is to be started before the results of drug-susceptibility testing of the patient's tubercle bacilli are reported, the treatment of choice be a combination of rifampin, ethambutol and a third drug such as capreomycin, ethionamide, pyrazinamide, kanamycin or cycloserine. Initial therapy with a four-drug combination including isoniazid, rifampin, ethambutol and another drug while drug-susceptibility results are awaited should also be considered because isoniazid is a highly effective drug and this study showed that in two thirds of the patients being retreated, the tubercle bacilli were still sensitive to it. I thank Miss Monica Wajs for her clerical assistance. References 1. JESSAMINE AG, ElDus L, NARASIMHAN V: Is primary drug-resistance to major antituberculous agents increasing? Can J Public Health 65: 363, 1974 2 ARMSTRONG AR: The prevalence in Canada of drug-resistant tubercie bacilli in newly discovered untreated patients with tuberculosis. Can Med Assoc 1 94: 420, 1966 3. ASHLEY MJ, ANDERSON TW, LB Rican WH: The influence of immigration on tuberculosis in Ontario. Am Rev Resp Dis 110: 137, 1974
Table I-Prevalence of drug resistance in 984 patients with pulmonary tuberculosis Patients without previous drug treatment (no. [and %I) Patients with previous drug treatment (no. [and %I) Canadian-born Immigrants (in Canada Recent immigrants Drug n=153 n=372 >Syr) n=240 n=219 n=831 Streptornycin 29 (18.9) 6 (1.6) 13 (5.4) 21(9.6) Para-aminosalicylic acid 17(11.1) 0 0 3 (1.4) Isoniazid 51(33.3) 6 (1.6) 4 (1.7) 9 (4.1) Ethambutol 2 (1.3) 0 0 0 Rifampin 0 0 0 0 Total no. of patients with resistant organisms* 54 (35.3)t 10 (2.7) 14 (5.8) 25 (11.4) *Some patients' organisms were resistant to more than one drug. tCanadian-born, 16 (20%); immigrants in Canada for more than 5 years, 13 (35.1%); recent immigrants, 25 (69.4%).
Total 40 (4.8) 3 (0.4) 19 (2.3) 0 0 49 (5.9)
CMA JOURNAL/NOVEMBER 8, 1975/VOL. 113 849
DPH
Summary: A review of the records of 984 patients admitted hospital from 1970 through 1973 with bacteriologically proven pulmonary tuberculosis showed bacterial resistance to one or more antituberculosis drugs in 103 (10.5%). Among the patients who had had previous drug treatment for tuberculosis the prevalence of drug resistance was 20% in the Canadian-born patients and 694% in the recent immigrants. Among the patients who had had no previous drug treatment the prevalence of drug resistance (primary resistance) was 2.7% in Canadian-born patients but 11.4% in recent immigrants. Because of the higher prevalence of drug resistance among recent immigrants and the finding in recent years that increasingly more tuberculosis patients in Ontario are recent immigrants, drug resistance in this group is likely to assume even more importance in the future.
to
Resume: La resistance aux medicaments chez des malades souffrant de tuberculose pulmonaire Une revue des dossiers de 984 malades hospitalises entre 1970 et 1973 pour une tuberculose pulmonaire demontree par des examens bacteriologiques a revele une resistance bacterienne a au moins un medicament antituberculeux chez 103 d'entre eux (10.5%). Parmi les malades traites auparavant par des antituberculeux, la frequence de la resistance medicamenteuse etait de 20% chez les personnes nees au Canada et de 69.4% chez les immigrants recemment entres au pays. Parmi les malades qui n'avaient Jamais auparavant recu de traitement antituberculeux, la prevalence de la resistance medicamenteuse (resistance primaire) etait de 2.7% chez les Canadiens de naissance mais de 11.4% chez les immigrants recents. Etant donne la plus grande prevalence de la resistance medicamenteuse parmi les immigrants recents, ainsi que le fait recemment etabli que de plus en plus des malades souffrant de tuberculose pulmonaire en Ontario sont des immigrants recents, il est probable que la prevalence de la resistance aux medicaments dans ce dernier groupe sera d'une importance croissante a I'avenir. From Toronto Hospital, Weston, Ont. Presented at the International Conference on Lung Diseases, Montreal, May 18 to 21, 1975 Reprint requests to: Dr. O.T. Cheung, Toronto Hospital, Weston, ON M9N 3M6
848 CMA JOURNAL/NOVEMBER 8, 1975/VOL. 113
Jessamine, Eidus and Narasimhan1 recently reported that
the prevalence of primary drug resistance in tuberculosis is noticeably high among recent immigrants to Canada. To confirm this finding I reviewed the records of patients with pulmonary tuberculosis admitted to Toronto Hospital, Weston during a 4-year period. Methods
The records of all patients with bacteriologically proven pulmonary tuberculosis, either those with newly diagnosed disease or those requiring retreatment, admitted to Toronto Hospital from 1970 through 1973 were reviewed; the data of those whose sputum was positive for drug-resistant My¬ cobacterium tuberculosis var. hominis were selected for analysis. Much of the bacteriologic work was performed by the laboratory services branch of the Ontario Ministry of Health. The patients were divided into three groups: (a) Cana¬ dian-born patients, (b) foreign-born patients who had lived in Canada for more than 5 years before admission to hos¬ pital and (c) foreign-born patients who had lived in Canada for 5 years or less before admission to hospital. For the purpose of this report the third group is designated as recent immigrants. Results
Of 984 patients with proven pulmonary tuberculosis ad¬ mitted to hospital the tubercle bacilli were resistant to anti¬ an overall prevalence of tuberculosis drugs in 103 10.5%. Of the 103 patients 63 were male and 40 were female. Twelve patients were 1 to 19 years old, 43 were 20 to 39 years, 25 were 40 to 59 years and 23 were 60 years or more. Twenty-six patients were Canadian-born and 77 26 from were foreign-born; 50 were recent immigrants Asia, 20 from continental Europe, 2 from South America, 1 from Africa and 1 from the British Isles. The findings on drug resistance are summarized in Table I. Among 153 patients who had had previous drug treat¬ ment for tuberculosis the prevalence of drug resistance was 35.3%. However, within this group the prevalence was 20% among 80 Canadian-born patients but 69.4% among 36 recent immigrants. Among 831 patients who had had no previous drug .
.
treatment for tuberculosis the overall prevalence of drug resistance (primary drug resistance) was 5.9%. The prevalence was only 2.7% among 372 Canadian-born patients but 11.4% among 219 recent immigrants. Thus, primary drug resistance was four times as common in recent immigrants as in Canadian-born patients. Of the 153 patients who had had previous drug treatment for tuberculosis the prevalence of resistance to isoniazid, streptomycin and para-aminosalicylic acid was high. Resistance to ethambutol was infrequent and that to rifampin, nonexistent. Of the other 831 patients the prevalence of primary drug resistance was low among the 372 Canadian-born patients, but relatively high among the 219 recent immigrants. There was no resistance to ethambutol or rifampin. The patients were treated with various combinations of antituberculosis drugs, including ethambutol in 78 patients and rifampin in 68 patients. The results of treatment were good: in 92% the sputum became negative within 6 months. Discussion In a nationwide survey on primary drug resistance in tuberculosis in Canada, carried out in 1963-64, Armstrong2 found that the tubercle bacilli of 4.8% of the patients were resistant to one or more antituberculosis drugs. In the present study, confined to patients in the Toronto area, the overall prevalence of primary drug resistance was 5.9%, being higher in recent immigrants (11.4%) than in Canadian-born patients (2.7%). Although Armstrong did not examine his data according to the country of origin of the patients or duration of residence in Canada when the diagnosis was made, it is probable that he surveyed relatively fewer recent immigrants than I did. The slightly higher rate of 5.9% in my study probably reflects this difference in the composition of the groups surveyed. It is probably safe to conclude that primary drug resistance in tuberculosis in Canada has not increased appreciably. The results of the present study have confirmed the
finding of Jessamine and colleagues1 that the prevalence of primary drug resistance is high among recent immigrants. Among the 41 immigrants they examined, resistance to one or more antituberculosis drugs was found in 19.5%. The prevalence of drug resistance among recent immigrants in my study was 11.4% - four times as high as the prevalence among Canadian-born patients. Although the number of instances of drug resistance noted in the 4-year period reviewed was not large, it is important that about one half of all instances were in recent immigrants. In a study on the influence of immigration on tuberculosis in Ontario in 1961-7 1 Ashley, Anderson and le Riche3 noted that increasingly more of the patients with tuberculosis in Ontario were recent immigrants. Drug resistance among recent immigrants is likely to assume more importance in the future. In view of the findings of this study, I suggest that when a recent immigrant is found to have active pulmonary tuberculosis, and if treatment is to be started before the results of drug-susceptibility testing of the patient's tubercle bacilli are reported, the treatment of choice be a combination of rifampin, ethambutol and a third drug such as capreomycin, ethionamide, pyrazinamide, kanamycin or cycloserine. Initial therapy with a four-drug combination including isoniazid, rifampin, ethambutol and another drug while drug-susceptibility results are awaited should also be considered because isoniazid is a highly effective drug and this study showed that in two thirds of the patients being retreated, the tubercle bacilli were still sensitive to it. I thank Miss Monica Wajs for her clerical assistance. References 1. JESSAMINE AG, ElDus L, NARASIMHAN V: Is primary drug-resistance to major antituberculous agents increasing? Can J Public Health 65: 363, 1974 2 ARMSTRONG AR: The prevalence in Canada of drug-resistant tubercie bacilli in newly discovered untreated patients with tuberculosis. Can Med Assoc 1 94: 420, 1966 3. ASHLEY MJ, ANDERSON TW, LB Rican WH: The influence of immigration on tuberculosis in Ontario. Am Rev Resp Dis 110: 137, 1974
Table I-Prevalence of drug resistance in 984 patients with pulmonary tuberculosis Patients without previous drug treatment (no. [and %I) Patients with previous drug treatment (no. [and %I) Canadian-born Immigrants (in Canada Recent immigrants Drug n=153 n=372 >Syr) n=240 n=219 n=831 Streptornycin 29 (18.9) 6 (1.6) 13 (5.4) 21(9.6) Para-aminosalicylic acid 17(11.1) 0 0 3 (1.4) Isoniazid 51(33.3) 6 (1.6) 4 (1.7) 9 (4.1) Ethambutol 2 (1.3) 0 0 0 Rifampin 0 0 0 0 Total no. of patients with resistant organisms* 54 (35.3)t 10 (2.7) 14 (5.8) 25 (11.4) *Some patients' organisms were resistant to more than one drug. tCanadian-born, 16 (20%); immigrants in Canada for more than 5 years, 13 (35.1%); recent immigrants, 25 (69.4%).
Total 40 (4.8) 3 (0.4) 19 (2.3) 0 0 49 (5.9)
CMA JOURNAL/NOVEMBER 8, 1975/VOL. 113 849
