Chemotherapy 23: 58-64 (1977)
Amoxycillin and Co-Trimoxazole in Acute Purulent Exacerbations of Chronic Bronchitis A. P ines , A. R. N andi , H. R aafat and M. R ahman East Herts Hospital and Herts and Essex Hospitals, Hertfordshire Key Words. Bronchitis • Exacerbations • Co-trimoxazole • Amoxycillin • Clinical state • Sputum • Bacteriology • Relapse • Side effects • Comparison • Single-blind trial Abstract. 100 hospital patients suffered from acute exacerbations of chronic bronchitis. 50 were treated with amoxycillin in a dose of 500 mg, three times a day for 10 days and the results compared with 50 patients treated with co-trimoxazole in a dose up to 480 mg trimethoprim and 2,400 mg of sulphamethoxazole daily in males, and two thirds of this dose in females. The trial was single-blind. During the acute phase of infection, both treatments were equally effective in clinical improve ment, conversion of the sputum from purulent to mucoid, diminution of quantity and elimination of pathogenic bacteria. Amoxycillin was quicker in sputum conver sion and gave less side effects, but the differences were not significant. During the 2-4 weeks following treatment, only a third of the patients who had received co-trimoxazole remained well and free from purulent relapse, as opposed to 72%> who had received amoxycillin, a difference significant at the 2°/o level.
Amoxycillin is a semi-synthetic penicillin related in structure to ampicillin, but with several advantages over the parent substance. Gastro-in testinal absorption is much better and is not affected by food [C roydon and S utherland , 1971]; it is more active in experimental infections [A cred et al., 1973]; skin rashes may be less. In chronic respiratory infections, intra bronchial concentrations remain high and bactericidal as long as the antibiotic is given, contrasting with the transient or poor con centrations found with most other antibiotics, including ampicillin [M ay and I ngold , 1972]; consequently these infections may relapse less often [B ü rg i , 1973], Co-trimoxazole (trimethoprim plus sulphamethoxazole) is more effec tive than ampicillin or tetracycline in customary doses [H ughes et al., 1969; L al and B halla , 1969; P ines et ai, 1972], It is now very widely given for chronic respiratory infections. However, strains of Haemophilus
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Introduction
P ines /N andi/R aafat /R ahman
59
influenzae have been isolated which have been claimed to be resistant to the combination [M ay and D avies, 1972]. Further, L acey and L ew is [1973] thought co-trimoxazole was not bactericidal in chronic respiratory infections. The relapse rate of infection might, thus, be high [M ay and D avies, 1972], To answer these questions we have compared amoxy cillin and co-trimoxazole in patients with acute purulent exacerbations of chronic bronchitis. Materials and Methods Plan of Investigation Because of practical difficulties, the study was single-blind. The assessments were made by the investigators who did not know which treatment each patient was re ceiving at the time. Treatment was allocated according to cards placed in sealed en velopes and drawn consecutively. The order of treatment was randomised [F isher and Y ates, 1970]. Treatment was for 10 days. Amoxycillin was given as 500 mg three times daily, giving blood levels roughly equal to ampicillin 3 g/day. Co-trimoxazole (Septrin) was given as two tablets three times daily, except in women where two tablets were given twice daily. The daily amounts of trimethoprim and sulphamethoxazole were 480 and 2,400 mg in the male patients, a higher dose than customarily given, but which we have found necessary in our patients [P ines et a!., 1972], 100 patients were treated, 50 in each group.
Patients All had a history of chronic bronchitis over many years with a recent acute pu rulent exacerbation. Two thirds were male and one third female in each group. Their principal features are shown in table I. There were no significant differences between the two groups. Some patients had antibiotic therapy in the week before
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Assessments These were fourfold. (1) The 24-hour sputum was examined each day for purulence and volume, by the attending doctor, or by a trained charge nurse. Four grades were used in assessment: mucoid, trace of purulence, moderately purulent and grossly purulent. (2) The patients’ clinical state was assessed by an independent doc tor before treatment began and at the end of treatment (11th day), and during the ensuing month. (3) The white cell count, sedimentation rate, empirical liver function and enzyme tests and peak flow rates were estimated before and after treatment. (4) All patients had to have purulent sputum before admission to the trial. Fresh speci mens of sputum were examined in the laboratory immediately before and after treatment and during the 1-month follow-up period. Standard loop-fulls were taken from the purulent part of the sputum and inoculated on to three plates: 10-15°/o horse blood, MacConkey’s and chocolate agar, the latter in 5% C 0 2 atmosphere. They were incubated at 37 °C for 24 h and antibiotic sensitivity was determined, us ing sub-cultures on oxoid medium and mast discs of 25 ug strength. With the Kirby-Bauer technique employed [Bauer et al., 1966], strains of H. influenzae were re garded as resistant when zones of inhibition were less than 19 mm to ampicillin and 7 mm to co-trimoxazole.
60
P in es /N andi /R aafat /R ahman
the start of the trial, usually ampicillin or tetracycline but without significant differ ences in the two groups. Those patients with other major chest diseases especially bronchiectasis, carci noma or asthma were excluded as were those so ill as to require parenteral chemo therapy. None gave a previous history of penicillin hypersensitivity.
Results Clinical Assessment The numbers improving in general state are shown in table II. Ap proximately three quarters of the patients in both groups improved. A few patients failed to improve or deteriorated. More patients treated with cotrimoxazole had side effects which were troublesome enough to require withdrawal of treatment. Three patients all treated with amoxycillin were withdrawn from the trial because other diagnoses were arrived at during the treatment. There was no significant difference between the two groups in clinical assessment on the 11th day. Sputum Changes The effects of the two regimes on sputum volume are shown in table III; with both there was reduction of volume in most patients. The assessments of sputum changes from purulent to mucoid by the 11th day are shown in table IV. In over two thirds in each group the spu tum became mucoid. The mean time for this to be achieved was longer with co-trimoxazole than amoxycillin, but the difference did not reach conventional significance (p>0.05). Mean improvement in peak flow rate was equal (29 and 34°/o).
Bacteriology More potential pathogens were isolated in those patients treated with amoxycillin before treatment began (table V). The total numbers of path ogens isolated after each treatment regime were halved in both groups. In
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Side Effects Among those patients treated with co-trimoxazole a rash appeared in four and a further four had severe vomiting, two with diarrhoea; the treat ment had to be changed in each case, when side effects disappeared. One patient given amoxycillin had a rash and another had severe diar rhoea; in both treatment had to be changed. These differences did not reach statistical significance (p>0.05). No laboratory abnormalities ap peared which could be attributed to the chemotherapy.
Amoxycillin and Co-Trimoxazole in Chronic Bronchitis
61
Table /. Comparability of patients before treatment Co-trimoxazole Number of patients Age, years Mean Range Mean weight, kg State of sputum Grossly purulent Moderately purulent Quantity of sputum, mean ml/24-hour collection period Peak flow rate, mean Slightly ill Moderately ill
Amoxycillin
50
50
71 39-91 59.1
70 43-90 62.2
19 31 49
19 31 57
151 3 47
139 2 48
There was no significant difference between the groups in any of these parameters (p >0.05). Table 11. Clinical assessment Assessment
Co-trimoxazole 11th day
Amoxycillin 11th day
Clinical improvement Failure Worse Withdrawn because of side effects
35 (70%) 5 2 8
39 (78%) 4 2 2 3/ 2 cancer, \ \ 1 stroke )
Withdrawn because of other diagnosis
0
There was no significant difference between the groups in any of these parameters.
four patients treated with co-trimoxazole isolates of H. influenzae were now resistant w hich had been sensitive to disc tests before treatm ent; all
Follow-up Patients remained in hospital for 2-4 weeks following the end of treat ment. Patients who had mucoid sputum at the end of the 10-day course of antibiotic were observed. Of 34 treated with co-trimoxazole whose spu tum had become mucoid and who had not received further chemotherapy,
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four patients relapsed. With the doubtful pathogens E. coli and S. aureus there was little clinical correlation with isolation, sensitivity or resistance [M ay, 1974].
P in es /N andi/R aafat /R ahman
62
Table III. Sputum volume by the Uth day Sputum volume, 24-hour collection period
Co-trimoxazole
Amoxycillin
Decreased Same Increased Withdrawn
30 7 5 8
30 10 5 5
There is no significant difference between the groups. Table IV. Assessment of sputum change, from purulent to mucoid by the 11th day
Mucoid Purulent Withdrawn Mean time for sputum to become mucoid, days
Co-trimoxazole
Amoxycillin
34(68%) 8 8 6.2
37 (74%) 8 5 4.1
There is no significant difference between the groups (p>0.05).
Both co-trimoxazole and amoxycillin have thus been shown to be a highly effective treatment in the acute phase of purulent chest infections, though co-trimoxazole was slower in achieving mucoid sputum and caused more side effects. However, treatment with co-trimoxazole al lowed a high rate of relapse of infection soon after treatment. Amoxycillin was significantly more effective in preventing relapse. This may be explained by the work of M ay and I ngold [1972] who showed that amoxycillin was unique in that bactericidal concentrations persisted in sputum well after the purulent phase of bronchial expectora tion had passed and postulated that patients would remain free of puru lent relapse for much longer than with other antibiotics. B urgi [1973] also found that freedom from relapse was longer with amoxycillin than with ampicillin. Consequently, we found co-trimoxazole inadequate in preventing relapse. M ay and D avies [1972] found a high isolation rate of H. influenzae which were resistant to trimethoprim-sulphamethoxazole by the disc test.
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only 12 still had mucoid sputum (34%). With patients treated with amox ycillin and who had not had further chemotherapy, 28 out of 37 (72%) still had mucoid sputum on follow-up. This difference is significant at the 2% level. Discussion
63
Amoxycillin and Co-Trimoxazole in Chronic Bronchitis Table V. Bacteriology Organism
co-trimoxazole before treatment total resistant
H. influenzae 11 S. pneumoniae 5 5 E. coli S. aureus 3 24
0 0 2 0
up to 1 month after treatment total resistant 5 1 4 2 12
4 0 3 0
amoxycillin before treatment total resistant 15 7 1 *T
5 34
0 0 3 3
up to 1 month after treatment total resistant 3 2 5 5 15
0 0 3 4
Most of their patients suffered from cystic fibrosis but some had chronic bronchitis. Trimethoprim but not sulphamethoxazole is found in good concentration in bronchial secretions [R eeves . 1971], while the bacterici dal action of the combination depends upon adequate concentrations of both components being present. This may explain why co-trimoxazole did not appear bactericidal in our patients, as shown both by the high rate of relapse and the emergence of resistant strains. A higher proportion of sul phamethoxazole might help but would be more toxic. Thus, in the context of chronic respiratory infection, a suitable sulphonamide for the co-trimoxazolc combination has yet to be found. The success that we have found with amoxycillin in preventing relapse is much higher than we have found with other oral antibiotics, such as te tracycline [P ines et al., 1972], chloramphenicol [P ines et al., 1972], ery thromycin [P ines et al., 1969], or cephalexin [P in es , 1974], Prophylactic treatment of chronic bronchitis is in disfavour (Leading article Lancet, 1975). Thus, amoxycillin seems to be the treatment of choice in patients with mild or moderate purulent exacerbations of chronic bronchitis. In those patients severely ill enough to require parenteral treatment an in jectable form of amoxycillin would be most desirable, but is not yet avail able. Higher doses of amoxycillin increase directly the sputum concentra tion to levels which will inhibit most strains of H. influenzae [I ngold , 1975] and may prove even more effective than the 500-mg dose we used.
We are grateful to the nursing staff of East Herts and Herts and Essex Hospitals for their help, to Dr. W. D. L insell and the Pathological Laboratory staff at Hert ford County and Herts and Essex Hospitals for their help, to Bencard for supplies of amoxycillin (Amoxil).
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
A cknowledgements
64
P in es /N andi/R aafat /R ahman
References A cred , P.; H unter , P. A.; M izen , L., and R olinson , G . N.: a-Amino-p-hydrox-
A. P ines , MD, FRCPE, Consultant Physician, East Herts Hospital, Stanstead Road, Hertford, Herts SG13 7HU (England)
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
ybenzylpenicillin (BRL-2333), a new semisynthetic penicillin in vivo evaluation. Antimicrob. Agents Chemother. 1970: 416-422 (1973). Bauer, A. W.; K irby, W. M.; S herrif , J. C., and T urck, M.: Antibiotic susceptibili ty testing by a standardized single disc method. Am. J. clin. Path. 45: 493 (1966). B urgi, H.: Klinisch-experimentelle Erfahrungen mit Amoxycillin bei chronischer Bronchitis. Chemotherapy 18: suppl., pp. 19-26 (1973). Croydon , E. A. P. and Sutherland , R.: a-Amino-p-hydroxybenzylpenicillin (BRL-2333), a new semisynthetic penicillin: absorption and excretion in man. Antimicrob. Agents Chemother. 1970. Am. Soc. Microbiol., p. 427 (1971). F isher , R. A. and Y ates, F.: Statistical tables for biological agricultural and medi cal research (Oliver & Boyd, Edinburgh 1970). H ughes , D. T. D.; D rew , D. C. M.; J ohnson , T. B. W., and J arvis, J. D.: Trimeth oprim and sulphamethoxazole in the treatment of chronic chest infections. Chemotherapy 14: 151 (1969). I ngold , A.: Sputum and serum levels of amoxycillin in chronic bronchial infections. Br. J. Dis. Chest 69: 211 (1975). L acey, R. W. and L ew is , E.: I s co-trimoxazole bactericidal in sputum? Br. med. J. iv: 165 (1973). L al, S. and Bhalla, K. K.: Comparison of tetracycline and trimethoprimsulphamethoxazole in acute episodes in chronic chest infections. Post-grad. med. J. 91: suppl., p. 45 (1969). Leading article: Antimicrobial treatment of chronic bronchitis. Lancet i: 505 (1975). M ay, J. R.: Chemotherapy of chronic bronchitis and allied disorders (English Uni versities Press, London 1974). M ay, J. R. and D avies, J.: Resistance of Haemophilus influenzae to trimethoprim. Br. med. J. iii: 376 (1972). M ay, J. R. and I ngold , A.: Amoxycillin in the treatment of chronic non-tuberculous bronchial infections. Br. J. Dis. Chest 66: 185 (1972). P ines , A.: Cephalosporins in bronchitis. Br. med. ii: 440 (1974) P ines , A.; R aafat, H .; G reenfield , J. S. B.; Siddiqui, G.; L enox -Sm ith , I., and L insell , W. D.: The management of purulent exacerbations of chronic bronchi tis - a comparison of co-trimoxazole and tetracycline. Practitioner 208:265 (1972). P ines , A.; R aafat, H.; G reenfield , J. S. B., and Solari, M.: Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis. Br. J. Dis. Chest 66: 107 (1972). P ines , A.; R aafat, H.; P lucinski, K.; G reenfield , J. S. B., and Solari, M.: A com parison of erythromycin, novobiocin, tetracycline and a novobiocin-tetracycline combination in purulent exacerbations of chronic bronchitis. Br. J. Dis. Chest 63: 206 (1969). Reeves , D. S.: Sulphamethoxazole/trimethroprim: the first two years. J. clin. Path. 24: 430-437 (1971).
Amoxycillin and Co-Trimoxazole in Acute Purulent Exacerbations of Chronic Bronchitis A. P ines , A. R. N andi , H. R aafat and M. R ahman East Herts Hospital and Herts and Essex Hospitals, Hertfordshire Key Words. Bronchitis • Exacerbations • Co-trimoxazole • Amoxycillin • Clinical state • Sputum • Bacteriology • Relapse • Side effects • Comparison • Single-blind trial Abstract. 100 hospital patients suffered from acute exacerbations of chronic bronchitis. 50 were treated with amoxycillin in a dose of 500 mg, three times a day for 10 days and the results compared with 50 patients treated with co-trimoxazole in a dose up to 480 mg trimethoprim and 2,400 mg of sulphamethoxazole daily in males, and two thirds of this dose in females. The trial was single-blind. During the acute phase of infection, both treatments were equally effective in clinical improve ment, conversion of the sputum from purulent to mucoid, diminution of quantity and elimination of pathogenic bacteria. Amoxycillin was quicker in sputum conver sion and gave less side effects, but the differences were not significant. During the 2-4 weeks following treatment, only a third of the patients who had received co-trimoxazole remained well and free from purulent relapse, as opposed to 72%> who had received amoxycillin, a difference significant at the 2°/o level.
Amoxycillin is a semi-synthetic penicillin related in structure to ampicillin, but with several advantages over the parent substance. Gastro-in testinal absorption is much better and is not affected by food [C roydon and S utherland , 1971]; it is more active in experimental infections [A cred et al., 1973]; skin rashes may be less. In chronic respiratory infections, intra bronchial concentrations remain high and bactericidal as long as the antibiotic is given, contrasting with the transient or poor con centrations found with most other antibiotics, including ampicillin [M ay and I ngold , 1972]; consequently these infections may relapse less often [B ü rg i , 1973], Co-trimoxazole (trimethoprim plus sulphamethoxazole) is more effec tive than ampicillin or tetracycline in customary doses [H ughes et al., 1969; L al and B halla , 1969; P ines et ai, 1972], It is now very widely given for chronic respiratory infections. However, strains of Haemophilus
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
Introduction
P ines /N andi/R aafat /R ahman
59
influenzae have been isolated which have been claimed to be resistant to the combination [M ay and D avies, 1972]. Further, L acey and L ew is [1973] thought co-trimoxazole was not bactericidal in chronic respiratory infections. The relapse rate of infection might, thus, be high [M ay and D avies, 1972], To answer these questions we have compared amoxy cillin and co-trimoxazole in patients with acute purulent exacerbations of chronic bronchitis. Materials and Methods Plan of Investigation Because of practical difficulties, the study was single-blind. The assessments were made by the investigators who did not know which treatment each patient was re ceiving at the time. Treatment was allocated according to cards placed in sealed en velopes and drawn consecutively. The order of treatment was randomised [F isher and Y ates, 1970]. Treatment was for 10 days. Amoxycillin was given as 500 mg three times daily, giving blood levels roughly equal to ampicillin 3 g/day. Co-trimoxazole (Septrin) was given as two tablets three times daily, except in women where two tablets were given twice daily. The daily amounts of trimethoprim and sulphamethoxazole were 480 and 2,400 mg in the male patients, a higher dose than customarily given, but which we have found necessary in our patients [P ines et a!., 1972], 100 patients were treated, 50 in each group.
Patients All had a history of chronic bronchitis over many years with a recent acute pu rulent exacerbation. Two thirds were male and one third female in each group. Their principal features are shown in table I. There were no significant differences between the two groups. Some patients had antibiotic therapy in the week before
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
Assessments These were fourfold. (1) The 24-hour sputum was examined each day for purulence and volume, by the attending doctor, or by a trained charge nurse. Four grades were used in assessment: mucoid, trace of purulence, moderately purulent and grossly purulent. (2) The patients’ clinical state was assessed by an independent doc tor before treatment began and at the end of treatment (11th day), and during the ensuing month. (3) The white cell count, sedimentation rate, empirical liver function and enzyme tests and peak flow rates were estimated before and after treatment. (4) All patients had to have purulent sputum before admission to the trial. Fresh speci mens of sputum were examined in the laboratory immediately before and after treatment and during the 1-month follow-up period. Standard loop-fulls were taken from the purulent part of the sputum and inoculated on to three plates: 10-15°/o horse blood, MacConkey’s and chocolate agar, the latter in 5% C 0 2 atmosphere. They were incubated at 37 °C for 24 h and antibiotic sensitivity was determined, us ing sub-cultures on oxoid medium and mast discs of 25 ug strength. With the Kirby-Bauer technique employed [Bauer et al., 1966], strains of H. influenzae were re garded as resistant when zones of inhibition were less than 19 mm to ampicillin and 7 mm to co-trimoxazole.
60
P in es /N andi /R aafat /R ahman
the start of the trial, usually ampicillin or tetracycline but without significant differ ences in the two groups. Those patients with other major chest diseases especially bronchiectasis, carci noma or asthma were excluded as were those so ill as to require parenteral chemo therapy. None gave a previous history of penicillin hypersensitivity.
Results Clinical Assessment The numbers improving in general state are shown in table II. Ap proximately three quarters of the patients in both groups improved. A few patients failed to improve or deteriorated. More patients treated with cotrimoxazole had side effects which were troublesome enough to require withdrawal of treatment. Three patients all treated with amoxycillin were withdrawn from the trial because other diagnoses were arrived at during the treatment. There was no significant difference between the two groups in clinical assessment on the 11th day. Sputum Changes The effects of the two regimes on sputum volume are shown in table III; with both there was reduction of volume in most patients. The assessments of sputum changes from purulent to mucoid by the 11th day are shown in table IV. In over two thirds in each group the spu tum became mucoid. The mean time for this to be achieved was longer with co-trimoxazole than amoxycillin, but the difference did not reach conventional significance (p>0.05). Mean improvement in peak flow rate was equal (29 and 34°/o).
Bacteriology More potential pathogens were isolated in those patients treated with amoxycillin before treatment began (table V). The total numbers of path ogens isolated after each treatment regime were halved in both groups. In
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
Side Effects Among those patients treated with co-trimoxazole a rash appeared in four and a further four had severe vomiting, two with diarrhoea; the treat ment had to be changed in each case, when side effects disappeared. One patient given amoxycillin had a rash and another had severe diar rhoea; in both treatment had to be changed. These differences did not reach statistical significance (p>0.05). No laboratory abnormalities ap peared which could be attributed to the chemotherapy.
Amoxycillin and Co-Trimoxazole in Chronic Bronchitis
61
Table /. Comparability of patients before treatment Co-trimoxazole Number of patients Age, years Mean Range Mean weight, kg State of sputum Grossly purulent Moderately purulent Quantity of sputum, mean ml/24-hour collection period Peak flow rate, mean Slightly ill Moderately ill
Amoxycillin
50
50
71 39-91 59.1
70 43-90 62.2
19 31 49
19 31 57
151 3 47
139 2 48
There was no significant difference between the groups in any of these parameters (p >0.05). Table 11. Clinical assessment Assessment
Co-trimoxazole 11th day
Amoxycillin 11th day
Clinical improvement Failure Worse Withdrawn because of side effects
35 (70%) 5 2 8
39 (78%) 4 2 2 3/ 2 cancer, \ \ 1 stroke )
Withdrawn because of other diagnosis
0
There was no significant difference between the groups in any of these parameters.
four patients treated with co-trimoxazole isolates of H. influenzae were now resistant w hich had been sensitive to disc tests before treatm ent; all
Follow-up Patients remained in hospital for 2-4 weeks following the end of treat ment. Patients who had mucoid sputum at the end of the 10-day course of antibiotic were observed. Of 34 treated with co-trimoxazole whose spu tum had become mucoid and who had not received further chemotherapy,
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
four patients relapsed. With the doubtful pathogens E. coli and S. aureus there was little clinical correlation with isolation, sensitivity or resistance [M ay, 1974].
P in es /N andi/R aafat /R ahman
62
Table III. Sputum volume by the Uth day Sputum volume, 24-hour collection period
Co-trimoxazole
Amoxycillin
Decreased Same Increased Withdrawn
30 7 5 8
30 10 5 5
There is no significant difference between the groups. Table IV. Assessment of sputum change, from purulent to mucoid by the 11th day
Mucoid Purulent Withdrawn Mean time for sputum to become mucoid, days
Co-trimoxazole
Amoxycillin
34(68%) 8 8 6.2
37 (74%) 8 5 4.1
There is no significant difference between the groups (p>0.05).
Both co-trimoxazole and amoxycillin have thus been shown to be a highly effective treatment in the acute phase of purulent chest infections, though co-trimoxazole was slower in achieving mucoid sputum and caused more side effects. However, treatment with co-trimoxazole al lowed a high rate of relapse of infection soon after treatment. Amoxycillin was significantly more effective in preventing relapse. This may be explained by the work of M ay and I ngold [1972] who showed that amoxycillin was unique in that bactericidal concentrations persisted in sputum well after the purulent phase of bronchial expectora tion had passed and postulated that patients would remain free of puru lent relapse for much longer than with other antibiotics. B urgi [1973] also found that freedom from relapse was longer with amoxycillin than with ampicillin. Consequently, we found co-trimoxazole inadequate in preventing relapse. M ay and D avies [1972] found a high isolation rate of H. influenzae which were resistant to trimethoprim-sulphamethoxazole by the disc test.
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
only 12 still had mucoid sputum (34%). With patients treated with amox ycillin and who had not had further chemotherapy, 28 out of 37 (72%) still had mucoid sputum on follow-up. This difference is significant at the 2% level. Discussion
63
Amoxycillin and Co-Trimoxazole in Chronic Bronchitis Table V. Bacteriology Organism
co-trimoxazole before treatment total resistant
H. influenzae 11 S. pneumoniae 5 5 E. coli S. aureus 3 24
0 0 2 0
up to 1 month after treatment total resistant 5 1 4 2 12
4 0 3 0
amoxycillin before treatment total resistant 15 7 1 *T
5 34
0 0 3 3
up to 1 month after treatment total resistant 3 2 5 5 15
0 0 3 4
Most of their patients suffered from cystic fibrosis but some had chronic bronchitis. Trimethoprim but not sulphamethoxazole is found in good concentration in bronchial secretions [R eeves . 1971], while the bacterici dal action of the combination depends upon adequate concentrations of both components being present. This may explain why co-trimoxazole did not appear bactericidal in our patients, as shown both by the high rate of relapse and the emergence of resistant strains. A higher proportion of sul phamethoxazole might help but would be more toxic. Thus, in the context of chronic respiratory infection, a suitable sulphonamide for the co-trimoxazolc combination has yet to be found. The success that we have found with amoxycillin in preventing relapse is much higher than we have found with other oral antibiotics, such as te tracycline [P ines et al., 1972], chloramphenicol [P ines et al., 1972], ery thromycin [P ines et al., 1969], or cephalexin [P in es , 1974], Prophylactic treatment of chronic bronchitis is in disfavour (Leading article Lancet, 1975). Thus, amoxycillin seems to be the treatment of choice in patients with mild or moderate purulent exacerbations of chronic bronchitis. In those patients severely ill enough to require parenteral treatment an in jectable form of amoxycillin would be most desirable, but is not yet avail able. Higher doses of amoxycillin increase directly the sputum concentra tion to levels which will inhibit most strains of H. influenzae [I ngold , 1975] and may prove even more effective than the 500-mg dose we used.
We are grateful to the nursing staff of East Herts and Herts and Essex Hospitals for their help, to Dr. W. D. L insell and the Pathological Laboratory staff at Hert ford County and Herts and Essex Hospitals for their help, to Bencard for supplies of amoxycillin (Amoxil).
Downloaded by: Access provided by the University of Michigan Library 141.216.78.40 - 1/11/2019 3:47:15 AM
A cknowledgements
64
P in es /N andi/R aafat /R ahman
References A cred , P.; H unter , P. A.; M izen , L., and R olinson , G . N.: a-Amino-p-hydrox-
A. P ines , MD, FRCPE, Consultant Physician, East Herts Hospital, Stanstead Road, Hertford, Herts SG13 7HU (England)
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