Abstract
CRP-guided antibiotic treatment reduces antibiotic prescription in acute exacerbation without change in treatment failure http://bit.ly/33IweWG
From the authors:
We thank M. Miravitlles and colleagues for their interest in our work [1]. They express concern about our failure rate: 24% at 10 days, and 45% at day 30; they feel that 31% of patients of the C-reactive protein (CRP) group and 46% of patients of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy group treated with antibiotics for acute COPD exacerbation is low in this high-risk population of hospitalised patients. Although treatment failure is high in our study, it reflects the severity of our population. Indeed, the proportion of patients on antimicrobials is lower than the outpatient study population in a recently published trial from the UK [2]; however, our COPD population is more severe and consists of hospitalised patients. Their concern is safety: have we caused harm in our patients by withholding antimicrobial treatment? First, in our study population, there was no significant difference in failure rates at days 10 and 30 between the CRP and GOLD group, which strongly argues against their point that antimicrobial treatment might have prevented harmful events (table 1). Neither failure during admission, nor relapse was significantly different between both study arms. Indeed, relapses among patients with acute exacerbation of COPD admitted to hospital are common [3], especially among individuals with a low forced expiratory volume in 1 s, but antimicrobial treatment may not necessarily prevent this, in particular among those that had low inflammatory markers. Slow recovery and early relapse have also been associated with increased inflammation, e.g. reflected by persistently increased CRP, and in patients characterised by chronic bronchitis [4], but whether these individuals might benefit from antimicrobial treatment if their CRP is below a given threshold has not been addressed in clinical studies [5]. An earlier study suggested that patients with CRP >50 mg·L−1 benefit more from antibiotic treatment compared to patients with CRP below this threshold [6]. Second, they argue that perhaps the active study arm treated with co-amoxiclav as the primary antimicrobial agent might have been inadequate. Although antimicrobial susceptibility data have not been listed in our paper, Pseudomonas spp. or other high-risk pathogens were covered if retrieved from sputum, and patients known to have colonisation with high-risk pathogens were provided with tailored antimicrobial regimens.
Third, we agree with M. Miravitlles and colleagues that our study was not powered to demonstrate safety beyond all reasonable doubt for patients in whom antimicrobial treatment was withheld based on the CRP decision rule alone [7]. Besides the initial reduction of antibiotics of more than 30% (from 46.2% to 31.7%) associated with the CRP algorithm, around 30% of the patients were additionally treated with antibiotics due to treatment failure (equally distributed between the two groups). Importantly, this did not result in an increase of adverse events or length of hospital stay.
Our study provides preliminary data suggesting safety, and therefore argues in favour of a larger international multicentre trial to address this question more definitively for patients with COPD exacerbation that are hospitalised.
Antimicrobial treatment may cause serious harm, first of all, for individuals themselves [8]. Differences across geographic regions suggest that outpatient antimicrobial prescription is at least in part culturally, not scientifically triggered [9]. Indeed Spain, Cyprus and Mongolia do worse than some other locales, e.g. the Netherlands. If we fail to reduce our antimicrobial footprint, sooner or later we will lose the war on antimicrobial resistance [10].
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Footnotes
Conflict of interest: H-J. Prins has nothing to disclose.
Conflict of interest: T.S. van der Werf has nothing to disclose.
Conflict of interest: W.G. Boersma reports grants from GSK and Foreest Medical School, during the conduct of the study.
- Received August 10, 2019.
- Accepted August 13, 2019.
- Copyright ©ERS 2019