Journal of Antimicrobial Chemotherapy (1991) 28, 141-156
Correspondence Cefaclor in the treatment of chronic brondutb
141
Bafora tnotmanl
After tn
Figure 1. The effect of two do»e* of cefaclor (14 days treatment) on sputum purulence. Score: 1 °> mucoid; 2 « mucopurulent; 3 — purulent (see Hill el al., 1986, for details). • , Cefaclor 500 mg three times daily; • , 1 g twice daily.
Fifthly, dosage of antibiotics may well be critical in some patients, as has been well demonstrated in subjects with purulent bronchiectasis who fail to respond (sputum becoming mucoid) to amoxycillin unless dosage is increased from 250 mg three times daily to 3 g sachets twice a day (Cole el al., 1983; Hill el al., 1986). The same probably applies to cefaclor. In our own studies we compared the effect of cefaclor on sputum purulence in patients with bronchiectasis. Our results are summarized in Figure 1 and show that 500 mg three times daily in these patients (n = 6) failed to change the sputum from purulent to mucoid. However in a similar group of patients (n = 8) 1 g cefaclor twice daily had a clearly demonstrable effect. These colour changes were associated with a reduction in neutrophil products and lung inflammation as described previously (Stockley, Hill & Morrison, 1984). Sputum cultures showed little difference before and after therapy. Thus a clinical benefit had occurred despite the bacteriology, perhaps due to a reduction in bacterial numbers rather than their presence. These results suggest that cefaclor has a role in bronchial infections, although patient selection and dosage is important In summary I feel that it is ethically acceptable to study more patients (Maesen et al., 1990), although I would suggest this should be done with higher dosages than those used previously. However I would make a plea that
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on June 11, 2015
Sir, I read with interest the article by Maesen, Geraedts & Davis (1990) on the efficacy of cefaclor A.F. in the management of acute purulent exacerbations of chronic bronchitis. Their findings and conclusions and closing statement are worthy of comment. Most of their correspondence revolves around sputum bacteriology, MIC data and sputum concentrations of cefaclor. They conclude that seven of eight patients receiving 250 mg three times daily failed treatment (persistent positive culture). Six of eight receiving 375 mg twice daily failed treatment but only three of eight receiving 500 mg twice dairy failed treatment. In addition two patients developed pneumonia and required a change in therapy. Failure was equated with__sptttu1n~ concentrations of cefaclortnat were below MIC of organisms isolated. Superficially this data suggests that cefaclor is ineffective until the dose is at least 500 mg twice daily. I feel there are several points worthy of comment Firstly, there is little definition of the patients, and many conditions can be lumped together under a general description of chronic bronchitis (smoke related bronchitis, emphysema, cystic fibrosis, bronchiectasis, asthma etc.). Secondly, most 'bronchitic' patients have viable organisms present in their sputum even when it is mucoid and the patient is apparently well. It is thus inappropriate to describe antibiotic effect in terms of bacteriology alone. Chronic bronchitis patients (cigarette smoke related) often deteriorate when their sputum is purulent and feel better when it is mucoid, even though bacteria are still present Thirdly, exacerbations may vary in severity from a change in sputum colour and increased breathlessness, to fever and interstitial shadowing on the chest X-ray. Clearly in the latter case an oral antibiotic is likely to be inappropriate. Fourthly, it may not be necessary for the antibiotic concentrations in the sputum to exceed the bacterial MIC for the patient to improve. Sub-MIC doses may reduce bacterial replication and enable host phagocytes (reflected in sputum purulence) to reduce bacterial numbers.
142
Correspondence
we note the patients' clinical response in addition to the bacterial results. R. A. STOCKLEY The Lung Invmmobiochemical Research Laboratory, The Clinical Teaching Block, The General Hospital, Steelhouse Lane, Birmingham B4 6NH. UK References
Sir, We read with interest the letter by Maesen, Geraedts & Davies (1990). We completely agree with the principles they suggest, particularly that the antibiotic concentration at the site of infection (i.e. in sputum and in bronchial epithelium) is crucial to the successful outcome of treatment. Furthermore, we agree that the dosage of antibiotic and the length of treatment need to be tailored to the clinical condition (including the type of disease present) of the patient rather than plucked from the air; this very point was made by one of us some years ago (Cole & Roberts, 1983a, b). For these very reasons, we believe that the results of the investigation by Maesen et al., (1990) can only be assessed in the tight of additional clinical information about the patients studied. Only with such information can the reader make decisions about applicability of their observations to particular groups of patients. We have experience of using cefaclor (standard preparation) in patients with bronchiectasis, a condition in which there are a number of barriers to the penetration of antibiotic into sputum. We have found cefaclor to be useful in these patients because many exacerbations are associated with 0-lactamase-produring strains of Haemophttus influenzae. However,
National Heart A. Lung Institute, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK. References Cole, P. & Roberts, D. E. (1983a). Ampicillin and alternatives. British Medical Journal 286, 1147. Cole, P. J. & Roberts, D. E. (1983*). High dose antibiotic is logical, effective and economical in treatment of severe bronchial sepsis. Lancet i, 248-9. Maesen, F. P. V., Geraedts, W. H. & Davies, B. I. (1990). Cefaclor in the treatment of chronic bronchitis. Journal of Antimicrobial Chemotherapy
26,456-8. Sir, We read with interest the letter by Maesen, Geraedts & Davies (1990). The authors suggest that inadequate levels of cefaclor are achieved in blood and sputum to treat hospitalized patients with exacerbations of chronic bronchitis. They base these observations on the results of a study in which three different dose regimens have been evaluated in just 24 patients, two-thirds of whom were treated with a small daily dose for this condition. When the eight patients treated with cefaclor 1500 mg daily are considered, five out of eight of these achieved satisfactory resolution with eradication of the organism; a success rate which compares well with that of other investigators, given the very small numbers (Brown, 1980). We have recently studied 51 patients admitted to hospital with exacerbations of chronic bronchitis, 26 of whom were treated with cefaclor 1500 mg daily and 25 with amoxycillin 1500 mg daily (Trigg et al., 1990). Such patients are at the most severe end of the disease spectrum, being elderly and frail, with severe airflow limitation (mean FEV1 0-7 ±0-2 L). Over 50% of our patients already had opportunistic colonizing organisms in the respiratory tract, presumably due to their debility and previous treatment with courses of
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on June 11, 2015
Cole, P. } . , Robert*, D. E., Davis, S. F. & Knight, R. K. (1983). A simple oral antimicrobial regimen effective in severe chronic bronchial suppuration associated with culturable Haemophilia influenzae Journal of Antimicrobial Chemotherapy 11, 109-13. Hill, S. L., Morrison, H. M., Burnett, D. & Stockley, R. A. (1986). Short term response of patients with bronchiectasis to treatment with amoxycillin given in standard or high doses orally or by inhalation. Thorax 41, 559-65. Maesen, F. P. V., Geraedts, W. H. & Davis, B. I. (1990). Cefaclor in the treatment of chronic bronchitis. Journal of Antimicrobial Chemotherapy 26,456-7. Stockley, R. A., Hill, S. L. & Morrison, H. M. (1984). Effect of antibiotic treatment on sputum elastase in bronchiectatk outpatients in the stable clinical state. Thorax 39, 414-9.
because of the problems with access of antibiotic to the site of infection, a dose of 2 g twice daily has usually been required for these patients with severe infection. The very low incidence of side effects with cefaclor, also noted by Maesen et al. (1990) permits a flexible dosage regimen; even with use of the aforementioned regimen of 2 g twice daily for a prolonged period of months, the drug proved safe. ROBERT WILSON PETER COLE
Correspondence Cefaclor in the treatment of chronic brondutb
141
Bafora tnotmanl
After tn
Figure 1. The effect of two do»e* of cefaclor (14 days treatment) on sputum purulence. Score: 1 °> mucoid; 2 « mucopurulent; 3 — purulent (see Hill el al., 1986, for details). • , Cefaclor 500 mg three times daily; • , 1 g twice daily.
Fifthly, dosage of antibiotics may well be critical in some patients, as has been well demonstrated in subjects with purulent bronchiectasis who fail to respond (sputum becoming mucoid) to amoxycillin unless dosage is increased from 250 mg three times daily to 3 g sachets twice a day (Cole el al., 1983; Hill el al., 1986). The same probably applies to cefaclor. In our own studies we compared the effect of cefaclor on sputum purulence in patients with bronchiectasis. Our results are summarized in Figure 1 and show that 500 mg three times daily in these patients (n = 6) failed to change the sputum from purulent to mucoid. However in a similar group of patients (n = 8) 1 g cefaclor twice daily had a clearly demonstrable effect. These colour changes were associated with a reduction in neutrophil products and lung inflammation as described previously (Stockley, Hill & Morrison, 1984). Sputum cultures showed little difference before and after therapy. Thus a clinical benefit had occurred despite the bacteriology, perhaps due to a reduction in bacterial numbers rather than their presence. These results suggest that cefaclor has a role in bronchial infections, although patient selection and dosage is important In summary I feel that it is ethically acceptable to study more patients (Maesen et al., 1990), although I would suggest this should be done with higher dosages than those used previously. However I would make a plea that
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on June 11, 2015
Sir, I read with interest the article by Maesen, Geraedts & Davis (1990) on the efficacy of cefaclor A.F. in the management of acute purulent exacerbations of chronic bronchitis. Their findings and conclusions and closing statement are worthy of comment. Most of their correspondence revolves around sputum bacteriology, MIC data and sputum concentrations of cefaclor. They conclude that seven of eight patients receiving 250 mg three times daily failed treatment (persistent positive culture). Six of eight receiving 375 mg twice daily failed treatment but only three of eight receiving 500 mg twice dairy failed treatment. In addition two patients developed pneumonia and required a change in therapy. Failure was equated with__sptttu1n~ concentrations of cefaclortnat were below MIC of organisms isolated. Superficially this data suggests that cefaclor is ineffective until the dose is at least 500 mg twice daily. I feel there are several points worthy of comment Firstly, there is little definition of the patients, and many conditions can be lumped together under a general description of chronic bronchitis (smoke related bronchitis, emphysema, cystic fibrosis, bronchiectasis, asthma etc.). Secondly, most 'bronchitic' patients have viable organisms present in their sputum even when it is mucoid and the patient is apparently well. It is thus inappropriate to describe antibiotic effect in terms of bacteriology alone. Chronic bronchitis patients (cigarette smoke related) often deteriorate when their sputum is purulent and feel better when it is mucoid, even though bacteria are still present Thirdly, exacerbations may vary in severity from a change in sputum colour and increased breathlessness, to fever and interstitial shadowing on the chest X-ray. Clearly in the latter case an oral antibiotic is likely to be inappropriate. Fourthly, it may not be necessary for the antibiotic concentrations in the sputum to exceed the bacterial MIC for the patient to improve. Sub-MIC doses may reduce bacterial replication and enable host phagocytes (reflected in sputum purulence) to reduce bacterial numbers.
142
Correspondence
we note the patients' clinical response in addition to the bacterial results. R. A. STOCKLEY The Lung Invmmobiochemical Research Laboratory, The Clinical Teaching Block, The General Hospital, Steelhouse Lane, Birmingham B4 6NH. UK References
Sir, We read with interest the letter by Maesen, Geraedts & Davies (1990). We completely agree with the principles they suggest, particularly that the antibiotic concentration at the site of infection (i.e. in sputum and in bronchial epithelium) is crucial to the successful outcome of treatment. Furthermore, we agree that the dosage of antibiotic and the length of treatment need to be tailored to the clinical condition (including the type of disease present) of the patient rather than plucked from the air; this very point was made by one of us some years ago (Cole & Roberts, 1983a, b). For these very reasons, we believe that the results of the investigation by Maesen et al., (1990) can only be assessed in the tight of additional clinical information about the patients studied. Only with such information can the reader make decisions about applicability of their observations to particular groups of patients. We have experience of using cefaclor (standard preparation) in patients with bronchiectasis, a condition in which there are a number of barriers to the penetration of antibiotic into sputum. We have found cefaclor to be useful in these patients because many exacerbations are associated with 0-lactamase-produring strains of Haemophttus influenzae. However,
National Heart A. Lung Institute, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK. References Cole, P. & Roberts, D. E. (1983a). Ampicillin and alternatives. British Medical Journal 286, 1147. Cole, P. J. & Roberts, D. E. (1983*). High dose antibiotic is logical, effective and economical in treatment of severe bronchial sepsis. Lancet i, 248-9. Maesen, F. P. V., Geraedts, W. H. & Davies, B. I. (1990). Cefaclor in the treatment of chronic bronchitis. Journal of Antimicrobial Chemotherapy
26,456-8. Sir, We read with interest the letter by Maesen, Geraedts & Davies (1990). The authors suggest that inadequate levels of cefaclor are achieved in blood and sputum to treat hospitalized patients with exacerbations of chronic bronchitis. They base these observations on the results of a study in which three different dose regimens have been evaluated in just 24 patients, two-thirds of whom were treated with a small daily dose for this condition. When the eight patients treated with cefaclor 1500 mg daily are considered, five out of eight of these achieved satisfactory resolution with eradication of the organism; a success rate which compares well with that of other investigators, given the very small numbers (Brown, 1980). We have recently studied 51 patients admitted to hospital with exacerbations of chronic bronchitis, 26 of whom were treated with cefaclor 1500 mg daily and 25 with amoxycillin 1500 mg daily (Trigg et al., 1990). Such patients are at the most severe end of the disease spectrum, being elderly and frail, with severe airflow limitation (mean FEV1 0-7 ±0-2 L). Over 50% of our patients already had opportunistic colonizing organisms in the respiratory tract, presumably due to their debility and previous treatment with courses of
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on June 11, 2015
Cole, P. } . , Robert*, D. E., Davis, S. F. & Knight, R. K. (1983). A simple oral antimicrobial regimen effective in severe chronic bronchial suppuration associated with culturable Haemophilia influenzae Journal of Antimicrobial Chemotherapy 11, 109-13. Hill, S. L., Morrison, H. M., Burnett, D. & Stockley, R. A. (1986). Short term response of patients with bronchiectasis to treatment with amoxycillin given in standard or high doses orally or by inhalation. Thorax 41, 559-65. Maesen, F. P. V., Geraedts, W. H. & Davis, B. I. (1990). Cefaclor in the treatment of chronic bronchitis. Journal of Antimicrobial Chemotherapy 26,456-7. Stockley, R. A., Hill, S. L. & Morrison, H. M. (1984). Effect of antibiotic treatment on sputum elastase in bronchiectatk outpatients in the stable clinical state. Thorax 39, 414-9.
because of the problems with access of antibiotic to the site of infection, a dose of 2 g twice daily has usually been required for these patients with severe infection. The very low incidence of side effects with cefaclor, also noted by Maesen et al. (1990) permits a flexible dosage regimen; even with use of the aforementioned regimen of 2 g twice daily for a prolonged period of months, the drug proved safe. ROBERT WILSON PETER COLE
