Are antibiotics needed in treatment of acute exacerbations of COPD (AECOPD)?
I have been reading a paper in the Blue journal from mid January which tries to address this question. As it was deemed editorial – worthy, it caught my eye.
To date, we administer antibiotics to patients with exacerbations of chronic obstructive airways disease based on the Anthonisen criteria. These were defined for a paper published in 1987 – now some years ago – and take into account increasing breathlessness, sputum volume and sputum purulence. There were limitations to that trial, not least among which was the absence of corticosteroids, such as prednisolone, from treatment regimes. We know that corticosteroids hasten clinical and physiological recovery and shorten hospital stays in patients with COPD. We don’t know that about antibiotics.
This recent, Dutch, study randomized 223 patients who between them suffered 265 episodes of exacerbation to receive either doxycycline 200mg daily for 7 days or placebo, in addition to a standardized treatment regime which included intraveinous and then oral prednisolone. Patients likely to have pneumonia (xray signs, fever) were excluded reasonably well. The primary endpoint was clinical response on Day 30, meaning that their symptoms and signs had either completely resolved or improved without getting worse again.
They found the following:
• At day 30 there was no significant difference between the groups
• At day 10, however (before which time you would generally hope to be sending someone home from hospital – the norm being around 7 to 9 days in our sort of institution), there was a slight difference in favour of the treatment group in terms of clinical response (80 vs 69% clinically responded. P=0.03). 67% of the doxy group were ‘cured’ at day 10, vs 51% of the placebo group (P=0.01). The difference was not statistically significant at day 30.
• More patients were changed from placebo to open-label antibiotic because of lack of efficacy than from doxy to open-label antibiotic for the same reason, at day 10 (15vs28%, P=0.01) and day 30 (33vs45%, P=0.13)
• Symptom scores were more improved at day 10 for the doxy group than for the placebo group, but not at day 30
• Microbiological outcomes varied at day 10. Common bugs were H.influenzae (41%), Pneumococcus (24%), Moraxella catarrhalis (22%). 52 of 78 patients in the doxy group who grew bacteria were cleared (67% ) vs 25 of 73 patients (34%) in the placebo group.
• 46 of the doxy group and 62 of the placebo group (37 vs 46%) had treatment failure.
• Withdrawal from the trial was similar in both groups, but 23 (17% ) of the placebo group withdrew for lack of efficacy, as opposed to only 8 (6%) of the doxy group withdrawing for that reason
The doxy seemed, in sub-group analysis, particularly beneficial in patients with increased sputum volume and purulence and a C-reactive protein of over 50.
The question raised by the article, and also by the editorial, is whether antibiotics really need to be added in to treatment regimes for patients with acute exacerbations of COPD. I suppose there are two ways of looking at this.
From my perspective, as doctor and holder of the keys to the pharmacy, it may well be correct to say that absence of benefit at 30 days is reason to withhold antibiotics from patients with acute exacerbations of COPD. It should be pointed out, however, that we all use corticosteroids in AECOPD in the absence of precisely the same benefit.
Why do we do this? Well, perhaps here we consider the patients perspective. We use corticosteroids because patients feel better faster, and because they stay in hospital for less time. We like it when our patients feel better faster, because psychologically any improvement is linked to our intervention, which in turn encourages future adherence to suggested treatment regimes.
If my doctor tells me that they are withholding a treatment with a narrow-spectrum antibiotic that will probably make me feel better quicker because it won’t still be having that effect in a month, I would probably be a little annoyed.
I would like to see a study setting out to prove whether what we already know about steroids. applies to antibiotics too: Do some patients feel better quicker, and get out of hospital sooner, if they take antibiotics –regardless of the effect at 30 days? Perhaps the study has been done. Time to get on PubMed.
Of course the argument is more complex than this. Antibiotic resistance is a major public health problem. However, the very real clinical issue of how we maintain our patients’ confidence by introducing treatments that work to help them achieve tangible health improvements, didn’t make it into the discussion about this paper in the AJRCCM.
Andrew
I have been reading a paper in the Blue journal from mid January which tries to address this question. As it was deemed editorial – worthy, it caught my eye.
To date, we administer antibiotics to patients with exacerbations of chronic obstructive airways disease based on the Anthonisen criteria. These were defined for a paper published in 1987 – now some years ago – and take into account increasing breathlessness, sputum volume and sputum purulence. There were limitations to that trial, not least among which was the absence of corticosteroids, such as prednisolone, from treatment regimes. We know that corticosteroids hasten clinical and physiological recovery and shorten hospital stays in patients with COPD. We don’t know that about antibiotics.
This recent, Dutch, study randomized 223 patients who between them suffered 265 episodes of exacerbation to receive either doxycycline 200mg daily for 7 days or placebo, in addition to a standardized treatment regime which included intraveinous and then oral prednisolone. Patients likely to have pneumonia (xray signs, fever) were excluded reasonably well. The primary endpoint was clinical response on Day 30, meaning that their symptoms and signs had either completely resolved or improved without getting worse again.
They found the following:
• At day 30 there was no significant difference between the groups
• At day 10, however (before which time you would generally hope to be sending someone home from hospital – the norm being around 7 to 9 days in our sort of institution), there was a slight difference in favour of the treatment group in terms of clinical response (80 vs 69% clinically responded. P=0.03). 67% of the doxy group were ‘cured’ at day 10, vs 51% of the placebo group (P=0.01). The difference was not statistically significant at day 30.
• More patients were changed from placebo to open-label antibiotic because of lack of efficacy than from doxy to open-label antibiotic for the same reason, at day 10 (15vs28%, P=0.01) and day 30 (33vs45%, P=0.13)
• Symptom scores were more improved at day 10 for the doxy group than for the placebo group, but not at day 30
• Microbiological outcomes varied at day 10. Common bugs were H.influenzae (41%), Pneumococcus (24%), Moraxella catarrhalis (22%). 52 of 78 patients in the doxy group who grew bacteria were cleared (67% ) vs 25 of 73 patients (34%) in the placebo group.
• 46 of the doxy group and 62 of the placebo group (37 vs 46%) had treatment failure.
• Withdrawal from the trial was similar in both groups, but 23 (17% ) of the placebo group withdrew for lack of efficacy, as opposed to only 8 (6%) of the doxy group withdrawing for that reason
The doxy seemed, in sub-group analysis, particularly beneficial in patients with increased sputum volume and purulence and a C-reactive protein of over 50.
The question raised by the article, and also by the editorial, is whether antibiotics really need to be added in to treatment regimes for patients with acute exacerbations of COPD. I suppose there are two ways of looking at this.
From my perspective, as doctor and holder of the keys to the pharmacy, it may well be correct to say that absence of benefit at 30 days is reason to withhold antibiotics from patients with acute exacerbations of COPD. It should be pointed out, however, that we all use corticosteroids in AECOPD in the absence of precisely the same benefit.
Why do we do this? Well, perhaps here we consider the patients perspective. We use corticosteroids because patients feel better faster, and because they stay in hospital for less time. We like it when our patients feel better faster, because psychologically any improvement is linked to our intervention, which in turn encourages future adherence to suggested treatment regimes.
If my doctor tells me that they are withholding a treatment with a narrow-spectrum antibiotic that will probably make me feel better quicker because it won’t still be having that effect in a month, I would probably be a little annoyed.
I would like to see a study setting out to prove whether what we already know about steroids. applies to antibiotics too: Do some patients feel better quicker, and get out of hospital sooner, if they take antibiotics –regardless of the effect at 30 days? Perhaps the study has been done. Time to get on PubMed.
Of course the argument is more complex than this. Antibiotic resistance is a major public health problem. However, the very real clinical issue of how we maintain our patients’ confidence by introducing treatments that work to help them achieve tangible health improvements, didn’t make it into the discussion about this paper in the AJRCCM.
Andrew
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