Symposium: Erythromycin

Scot. med, J., 1977, 22: 355

ERYTHROMYCIN IN RESPIRATORY TRACT INFECTION J. C Gould

Central Microbiological Laboratories, Western General Hospital, Edinburgh

Summary. One of the main uses of erythromycin in respiratory tract infection has been in the treatment of acute streptococcal tonsillitis as an alternative to penicillin. Studies on the quantitative bacteriology of tonsils obtained at tonsillectomy have shown large numbers of both haemolytic streptococci and Haemophilus species in most samples and these organisms can be effectively reduced in number by preoperative treatment with antibiotics such as erythromycin. Such investigations suggest that erythromycin might have wider use in the treatment of respiratory tract infections, particularly where Haemophilus influenzae and other Haemophilus species are involved. Apart from specific infections such as those due to Mycoplasma pneumoniae, erythromycin is effective in the treatment of acute pneumonia due to organisms such as the pneumococcus, and this paper reports the further use of erythromycin in the treatment ofacute exacerbations ofchronic bronchitis where the clinical and bacteriological effects of treatment with this antibiotic are compared with those of ampicillin. E S P I R A TO R Y tract infection is a very Other investigations recently carried out, common cause of morbidity, but the exact however (Gould, 1972), suggest that bacteria relationship of the varied microflora of the res- other than haemolytic streptococci are somepiratory tract to specific infections and the use times significant in upper respiratory tract of antimicrobial agents in treatment are con- infections and one of the most important of troversial. these is Haemophilus, of which a number of In this presentation I wish to illustrate a species occur both normally and in disease in rationale for the use of erythromycin in infec- the respiratory tract. Some strains such as tions of the upper and lower respiratory tract Haemophilus parainfluenzae and Haemophilus with two examples of commonly occurring haemolyticus, are haemolytic on blood agar infections encountered both in general practice culture medium and may, on primary culture, and in hospital. The first is sore throat, an appear similar to haemolytic streptococci. Such example of an upper respiratory tract infection organisms are isolated in large numbers from and the second, acute exacerbations of chronic cases of tonsillitis but can be distinguished by bronchitis, an infection of the lower respiratory their greater resistance to bacitracin, an agent which may be usefully incorporated in the tract. culture medium (Jarvis & Ewins, 1968). These observations encouraged a detailed Tonsillitis The commonest bacterial cause of sore throat, bacteriological examination of tonsillar tissue in particularly follicular tonsillitis, is believed to the hope that more information about the signibe the beta-haemolytic streptococcus, most ficance of Haemophilus species and the in vivo frequently of Group A. These organisms are action of antibiotics on organisms in these always sensitive to penicillin and erythromycin, tissues could be obtained (Gould, 1976). but a variable proportion are reported resistant, to tetracycline. This is the basis of the usual Materials andmethods advice to treat patients who have sore throats Apart from swabs of the fauces of patients with penicillin and to use erythromycin as the suffering from sore throat, the only material most desirable alternative when there are readily available for examination is tissue contra-indications to the use of penicillin. obtained at tonsillectomy and the data reported

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are from a study of such fresh tonsil tissue obtained from children between 4 and 11 years of age. These children had had throat swabs taken on a number of occasions before operation and their tonsils were sent immediately for bacteriological examination. A second series of similar children was examined to whom antibiotics had been administered during the week before operation and in them antibiotic assay was carried out on their blood and tonsil tissue. The methods of examination of the swabs and quantitative examinations of the tonsils have been detailed elsewhere (Gould, 1976). Of 500 children appearing at an ear, nose and throat clinic and who had their throats swabbed, only 30 per cent yielded Streptococcus pyogenes and 19 per cent Haemophilus species. In contrast, examination of the tonsil tissue from a proportion of them yielded large numbers (approximately 10 7 jg.) ofboth organisms (Table I). Other organisms such as the Table I. Bacteriological examination of tonsil tissue: 133 cases. 74 (56%) ~-haemolytic streptococci Haemophilus 85 (64%) Haemolytic streptococcus and Haemophilus 30 (23%) Other organisms predominant 19 (15%) Staphylococcus, Pneumococcus, Neisseria and Pasteurella were present less frequently and usually in smaller numbers. This suggests that Streptococcus pyogenes and Haemophilus species are most frequently involved in infection of the tonsils and as both organisms are usually sensitive to erythromycin and a number of other antibiotics, it was of interest to measure the effect of treatment with them and to relate the results to tissue and blood concentrations. Obviously it was not possible to carry out these comparisons in individual patients so that the experiment compared series of similar patients given erythromycin (Group A) another

Table II.

Treatment groups.

Group A: Erythromycin ethyl succinate (Erythroped) Oral syrup 200 mgm. in 5 mI. q.i.d. for children less than 8 years. 400 mgm. in 5 ml. q.i.d. for children over 8 years. Group B: Penicillin 'V' potassium salt 125 mgm. in 5 ml. of syrup q.i.d. for children less than 5 years. 250 mgm. in 5 ml, of syrup q.i.d. for children over 5 years. Group C: No treatment given penicillin (Group B) and a third no specific treatment (Group C) (Table II).

Results of treatment (Table III) Both antibiotics showed their antistreptococcal effect as this organism was recovered from only a few specimens of tonsils in both treatment groups and in much reduced numbers compared with the untreated control group. Haemophilus was also recovered from only a minority of specimens within the two antibiotic treatment groups and the effect of erythromycin was considerably greater as shown by the average number of organisms recovered. This in vivo activity of erythromycin compared with that of penicillin is thus a basis for recommending the use of erythromycin in the treatment of upper respiratory tract infection. The activity of erythromycin against Haemophi/us is especially important since routine examinations of cases of upper respiratory tract infection have shown these organisms to occur in more than 20 per cent of such patients in significant numbers (Gould, 1977). Treatment of these patients with erythromycin may sometimes be shown to be more effective than penicillin. The sensitivity of the organisms isolated from the tonsils is shown in Table IV. All the strains of Streptococcus pyogenes were sensitive to less than 0.5 pg./ml. of penicillin and less

Table III. Tonsils: bacteriological results of treatment. Number with Mean Treatment regime Number of Number with Mean number of patients residual number of residual Haemophilus organisms/g. Streptococcus organisms/g. No treatment (Group C) Penicillin (Group B) Erythromycin (Group A) 356

19 20 20

15 7 4

15 5 4

107 3 8

X

X

104 104

Erythromycin in Respiratory Tract Infection

Table IV.

Organism

Antibiotic sensitivity of strains isolated from no treatment series (Group C). No. of strains Number sensitive to

Streptococcus pyogenes 122 Haemophilus 98 Staphylococcus 6 Pneumococcus 8 From treatment series (Groups A and B) Streptococcus py ogenes 16 24 Haemophilus Staphylococcus 5

-------------------, Penicillin

Erythromycin

0.5 f.lg./ml.

2.5

12.5

25 pg./ml.

122 30 3 8

122 58 4 8

81 2

98

16 10 4

16 14 4

18 1

24

tetracyclines and ampicillin are clinically effective and widely used. Although the Pneumococcus is highly sensitive to erythromycin this antibiotic has not been widely advocated for the treatment of the exacerbations, possibly because some strains of Haemophilus are less susceptible in vitro. Thus the clinical and bacteriological efficiency of erythromycin in the treatment of exacerbations of bronchitis Table V. Mean concentration of antibiotic in was measured and compared with ampicillin in a double blind controlled trial. The clinical sera and tonsils following 10 days treatment. progress of these patients was assessed by Erythromycin Penicillin (Group A) (Group B) measuring the time taken to convert their sputum from purulent to mucoid. Figure I pg./ml. pg./ml. illustrates the rate of conversion of the sputa Sera 0.8 0.8 from purulent to mucoid during treatment with Tonsils 2.2 1.3 ampicillin or erythromycin. The proportion of The concentrations of the antibiotics patients who converted on the first day followobtained in the tissues (Table V) are greater ing the start of treatment was small, although than the M.LC. of both erythromycin or peni- higher with ampicillin than erythromycin, but cillin for Streptococcus pyogenes, but only as the 10th day of treatment is approached, marginally so or less than the M.LC. for the the difference between the two antibiotics majority of strains of Haemophilus. This result becomes much less and the clinical performance correlates with the number of surviving Haemo- of the two antibiotics is, therefore, similar. The philus organisms retrieved from the tonsils fol- clinical success rate of treatment with lowing treatment with both penicillin and ampicillin was thus 93 per cent and with erythromycin (Table III). erythromycin 88 per cent (Willey, Gould & Grant, 1977). Acute exacerbations of chronic bronchitis The bacteriological results (Table VI) show Most observers agree that exacerbations of that of the 27 exacerbations treated with ampichronic bronchitis are associated with Haemo- cillin and 34 with erythromycin, that all had philus influenzae and the Pneumococcus. Anti- Pneumococcus or Haemophilus present in microbial agents active against these organisms numbers greater than 106 jml. before treatment. have been found successful in the treatment of After treatment only one patient receiving exacerbations and this is correlated with a erythromycin and one on ampicillin yielded reduction of pathogens in the sputum, although residual Pneumococci; in two cases treated with eradication is difficult (May, 1972). Thus the ampicillin, residual Haemophilus was isolated, than 2.5 pg.jml. of erythromycin. Approximately 30 per cent of Haemophilus strains were sensitive to 0.5 pg./ml. of erythromycin, 50 per cent to 2.5 pg.jml. and the remainder to less than 25 pg.jml. The antibiotic resistance of strains isolated from the series treated with antibiotic is no greater than that of the strains in the untreated series so that it seems unlikely that resistance develops as a result of treatment.

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Erythromycin in respiratory tract infection.

Symposium: Erythromycin Scot. med, J., 1977, 22: 355 ERYTHROMYCIN IN RESPIRATORY TRACT INFECTION J. C Gould Central Microbiological Laboratories, W...
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