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Current Medical Research and Opinion
Comparative study on the use of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infections
Vol. 3, No. 4, 1975
M. A. Sallam," M.R.C.P.(Lon.) and
I.A.Sallam, F.R.C.S.(Ed. and Eng.), Ph.D.(Glas.) Department of Medicine, K.O.C. Hospital, Kuwait, Arabian Gulf'
Cum. med. RCS.Opin., (l975), 3,229.
Received: 3rd April 1975
Summary A double-blind trial M'as cussied out on 116 putients with lower. respiratory tract infection and systemic manyestations. One gsoup received co-tsimoxazole (480 mg. trimethoprim and 2,400 mg. sulphamethoxazole daily), and the other group received 2 g. tetracycline daily. The trial, as judged bj1 clinical improvements, the seduction of purulent sputum and the rate of eradication of infection, showed a better result with co-trimoxazole. The incidence of side-efects were higher in the group seceiving tetracycline compared with those seceiving co-tsimoxazole. Key wosds: Co-tsinioxazole - tetracycline - respiratosy tract infections
Introduction Co-trimoxazole('Septrin')t, a combination of trimethoprimand sulphamethoxazole, has proved its effectiveness against a wide spectrum of bacterial invaders of the respiratory tract. The present study compares its effectiveness with tetracycline hydrochloride in controlling lower chest infection. The results of a double-blind comparison are presented.
Materials and methods One hundred and sixteen adult patients of both sexes with acute lower respiratory tract infection and systemic manifestations were included in this study. The relevant criteria for inclusion were the presence of a definite rise in body temperature, cough with purulent expectoration, and chest signs of lower tract respiratory infection confirmed by X-ray appearances. Patients were divided into two groups at random according to their treatment regime. Half the patients received co-trimoxazole in a dose of 480 mg. trimethoprim and 2,400 mg. sulphamethoxazole daily. The rest were put on tetracycline hydrochloride in a dose of 500 mg. 6-hourly. All patients were treated in Doha Hospital, Qatar, during the course of 14 years. Pregnant women, children under 15 years, patients over the age of 65, and patients who were desperately ill or those with any associated disease or complication, were excluded from the study. *Head of Department; ttrade mark Wellcome Laboratories 229
Curr Med Res Opin Downloaded from informahealthcare.com by Flinders University of South Australia on 01/10/15 For personal use only.
Comparative study on the use of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infections
The assessment of these patients was based on: (i) the return of body temperature to a normal level; (ii) the reduction in the amount of expectoration; and (iii) the clearing of the chest X-ray. Results were classified as good if all three criteria were fulfilled and as moderate if patients fulfilled the first two criteria only, but there was delayed clearance of the X-ray over 10 days. Results were regarded as poor in patients who did not show any improvements and who needed a change of antibiotic therapy after 1 week from the onset of the treatment.
Results The results are summarised in Table I. Table I. Results of treatment in 116 patients with lower respiratory tract infections Result
Co-trimoxazole
Tetracycline
No.
%
No.
%
Good Moderate Poor
36 19 3
62.0 32.8 5.2
19 23 16
32.8 39.6 27.6
Total
58
58
Clinical improvements as shown by improvement of general condition, change of purulent sputum into mucoid was present in 55 patients ( 9 5 % ) receiving cotrimoxazole, while it occurred in only 42 (72 %) patients (p < 0.01) receiving tetracycline. Complete clearing of the X-ray picture within 10 days occurred in 36 patients in the group receiving co-trimoxazole, but was reported in only 19 patients receiving tetracycline (p < 0.001). Poor results occurred in 3 patients receiving co-trimoxazole and they needed a change of antibiotic. Two of these patients showed the presence of H.infruenzae which responded satisfactorily to ampicillin. The third patient had E. coli infection and responded to gentamicin 1 week after the start of the treatment. In the group receiving tetracycline, 16 patients showed poor results. The antibiotic therapy was changed according to the sensitivity tests. Six of these patients responded to cotrimoxazole. Control of infection was difficult in 3 patients, one with ps. aeruginosa and 2 with mixed infection.
Side-efec ts Various gastro-intestinal symptoms occurred in 7 patients receiving co-trimoxazole and in 14 receiving tetracycline. There was no need to stop the drug in any of them. On the other hand, skin rashes were noticed in 2 patients receiving co-trimoxazole and in 4 patients receiving tetracycline. No leucopenia was reported in any of our cases. 230
M. A. Sallam and 1. A. Sallam
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Discussion The synergistic effect of trimethoprim and sulphamethoxazole has been shown previously' and it has also been reported that while both drugs are bacteriostatic, they exhibit bactericidal action when used in combination.2 Previous reports of controlled comparative studies have shown the value of cotrimoxazole in the treatment of patients with chronic bronchitis presenting with acute exacerbation.3-5 The present study shows its effectiveness as a means for the management of acute lower respiratory tract infection. The results prove its superiority over tetracycline hydrochloride in controlling the infection in these patients. This is perhaps due to its effectiveness on various types of bacteria involved in lower respiratory tract infection.' This offers a great advantage in situations where bacteriological examination is difficult to obtain, as in peripheral hospitals. Although the highest incidence of side-effects was gastro-intestinal symptoms, none of them needed discontinuation of the drug, but a higher incidence was present in the group receiving tetracycline. There was no incidence of leucopenia with cotrimoxazole in our study and although Hughes3 reported 2 cases of leucopenia in 50 patients studied with reduced white cell count, both patients returned to normal after the stoppage of the drug. Other workers have shown that its effect on the haematopoietic system appears to be minimal or none at all, in spite of theoretical consideration and proIonged usage of c o - t r i m ~ x a z o l e . ~ + ~ In conclusion, co-trimoxazole can be regarded as a very useful method of treating patients with acute lower respiratory infection. The low incidence of side-effects and the high cure rate compared with tetracycline indicates its superiority over tetracycline and justifies its use as a first line of treatment in such situations.
References 1 . Bushby, S. R. M., and Hitchings, G. H., (1968). Trimethoprim, a sulphonamide potentiater. Brit. J. Pharmacol., 33,72. 2. Darell, J. H., Garrod, L. P., and Waterworth, P. M., (1968). Trimethoprim:laboratory and clinical studies. J. clin. Pafhol., 21,202. 3 . Hughes, D. T. D., (1969). Single-blind comparative trial of trimethoprim-sulphamethoxazole and ampicillin in the treatment of exacerbations of chronic bronchitis. Brit. med. J., 4,470. 4. Lal, S., and Bhalla, K. K., (1969). Comparison of tetracycline and trimethoprim-sulphamethoxazole in acute episodes in chronic chest infection. Postgrad, nzed J., 45, Suppl., 91. 5. Pines, A., Raafat, H., Greefield, J. S. B., Siddiqui, G., Lennox-Smith, I., and Linsell, W. D., (I 972). The management of purulent exacerbationsof chronic bronchitis. Pracfifioner,208,265.
23 I
Current Medical Research and Opinion
Comparative study on the use of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infections
Vol. 3, No. 4, 1975
M. A. Sallam," M.R.C.P.(Lon.) and
I.A.Sallam, F.R.C.S.(Ed. and Eng.), Ph.D.(Glas.) Department of Medicine, K.O.C. Hospital, Kuwait, Arabian Gulf'
Cum. med. RCS.Opin., (l975), 3,229.
Received: 3rd April 1975
Summary A double-blind trial M'as cussied out on 116 putients with lower. respiratory tract infection and systemic manyestations. One gsoup received co-tsimoxazole (480 mg. trimethoprim and 2,400 mg. sulphamethoxazole daily), and the other group received 2 g. tetracycline daily. The trial, as judged bj1 clinical improvements, the seduction of purulent sputum and the rate of eradication of infection, showed a better result with co-trimoxazole. The incidence of side-efects were higher in the group seceiving tetracycline compared with those seceiving co-tsimoxazole. Key wosds: Co-tsinioxazole - tetracycline - respiratosy tract infections
Introduction Co-trimoxazole('Septrin')t, a combination of trimethoprimand sulphamethoxazole, has proved its effectiveness against a wide spectrum of bacterial invaders of the respiratory tract. The present study compares its effectiveness with tetracycline hydrochloride in controlling lower chest infection. The results of a double-blind comparison are presented.
Materials and methods One hundred and sixteen adult patients of both sexes with acute lower respiratory tract infection and systemic manifestations were included in this study. The relevant criteria for inclusion were the presence of a definite rise in body temperature, cough with purulent expectoration, and chest signs of lower tract respiratory infection confirmed by X-ray appearances. Patients were divided into two groups at random according to their treatment regime. Half the patients received co-trimoxazole in a dose of 480 mg. trimethoprim and 2,400 mg. sulphamethoxazole daily. The rest were put on tetracycline hydrochloride in a dose of 500 mg. 6-hourly. All patients were treated in Doha Hospital, Qatar, during the course of 14 years. Pregnant women, children under 15 years, patients over the age of 65, and patients who were desperately ill or those with any associated disease or complication, were excluded from the study. *Head of Department; ttrade mark Wellcome Laboratories 229
Curr Med Res Opin Downloaded from informahealthcare.com by Flinders University of South Australia on 01/10/15 For personal use only.
Comparative study on the use of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infections
The assessment of these patients was based on: (i) the return of body temperature to a normal level; (ii) the reduction in the amount of expectoration; and (iii) the clearing of the chest X-ray. Results were classified as good if all three criteria were fulfilled and as moderate if patients fulfilled the first two criteria only, but there was delayed clearance of the X-ray over 10 days. Results were regarded as poor in patients who did not show any improvements and who needed a change of antibiotic therapy after 1 week from the onset of the treatment.
Results The results are summarised in Table I. Table I. Results of treatment in 116 patients with lower respiratory tract infections Result
Co-trimoxazole
Tetracycline
No.
%
No.
%
Good Moderate Poor
36 19 3
62.0 32.8 5.2
19 23 16
32.8 39.6 27.6
Total
58
58
Clinical improvements as shown by improvement of general condition, change of purulent sputum into mucoid was present in 55 patients ( 9 5 % ) receiving cotrimoxazole, while it occurred in only 42 (72 %) patients (p < 0.01) receiving tetracycline. Complete clearing of the X-ray picture within 10 days occurred in 36 patients in the group receiving co-trimoxazole, but was reported in only 19 patients receiving tetracycline (p < 0.001). Poor results occurred in 3 patients receiving co-trimoxazole and they needed a change of antibiotic. Two of these patients showed the presence of H.infruenzae which responded satisfactorily to ampicillin. The third patient had E. coli infection and responded to gentamicin 1 week after the start of the treatment. In the group receiving tetracycline, 16 patients showed poor results. The antibiotic therapy was changed according to the sensitivity tests. Six of these patients responded to cotrimoxazole. Control of infection was difficult in 3 patients, one with ps. aeruginosa and 2 with mixed infection.
Side-efec ts Various gastro-intestinal symptoms occurred in 7 patients receiving co-trimoxazole and in 14 receiving tetracycline. There was no need to stop the drug in any of them. On the other hand, skin rashes were noticed in 2 patients receiving co-trimoxazole and in 4 patients receiving tetracycline. No leucopenia was reported in any of our cases. 230
M. A. Sallam and 1. A. Sallam
Curr Med Res Opin Downloaded from informahealthcare.com by Flinders University of South Australia on 01/10/15 For personal use only.
Discussion The synergistic effect of trimethoprim and sulphamethoxazole has been shown previously' and it has also been reported that while both drugs are bacteriostatic, they exhibit bactericidal action when used in combination.2 Previous reports of controlled comparative studies have shown the value of cotrimoxazole in the treatment of patients with chronic bronchitis presenting with acute exacerbation.3-5 The present study shows its effectiveness as a means for the management of acute lower respiratory tract infection. The results prove its superiority over tetracycline hydrochloride in controlling the infection in these patients. This is perhaps due to its effectiveness on various types of bacteria involved in lower respiratory tract infection.' This offers a great advantage in situations where bacteriological examination is difficult to obtain, as in peripheral hospitals. Although the highest incidence of side-effects was gastro-intestinal symptoms, none of them needed discontinuation of the drug, but a higher incidence was present in the group receiving tetracycline. There was no incidence of leucopenia with cotrimoxazole in our study and although Hughes3 reported 2 cases of leucopenia in 50 patients studied with reduced white cell count, both patients returned to normal after the stoppage of the drug. Other workers have shown that its effect on the haematopoietic system appears to be minimal or none at all, in spite of theoretical consideration and proIonged usage of c o - t r i m ~ x a z o l e . ~ + ~ In conclusion, co-trimoxazole can be regarded as a very useful method of treating patients with acute lower respiratory infection. The low incidence of side-effects and the high cure rate compared with tetracycline indicates its superiority over tetracycline and justifies its use as a first line of treatment in such situations.
References 1 . Bushby, S. R. M., and Hitchings, G. H., (1968). Trimethoprim, a sulphonamide potentiater. Brit. J. Pharmacol., 33,72. 2. Darell, J. H., Garrod, L. P., and Waterworth, P. M., (1968). Trimethoprim:laboratory and clinical studies. J. clin. Pafhol., 21,202. 3 . Hughes, D. T. D., (1969). Single-blind comparative trial of trimethoprim-sulphamethoxazole and ampicillin in the treatment of exacerbations of chronic bronchitis. Brit. med. J., 4,470. 4. Lal, S., and Bhalla, K. K., (1969). Comparison of tetracycline and trimethoprim-sulphamethoxazole in acute episodes in chronic chest infection. Postgrad, nzed J., 45, Suppl., 91. 5. Pines, A., Raafat, H., Greefield, J. S. B., Siddiqui, G., Lennox-Smith, I., and Linsell, W. D., (I 972). The management of purulent exacerbationsof chronic bronchitis. Pracfifioner,208,265.
23 I
