Abstract
A reduction in antibiotic use to treat COPD must be safe for the patient http://bit.ly/2GxGpTO
To the Editor:
We read with great interest the well-conducted clinical trial on C-reactive protein (CRP)-guided antibiotic treatment in admitted patients with acute exacerbations of COPD by Prins et al. [1]. This is a study showing that the use of CRP can potentially assist clinicians in making more prudent use of antibiotics in patients with severe exacerbations, as has also been found in the primary care setting [2]. One of the striking results is, however, the disturbingly high rate of treatment failure observed of approximately 24% at 10 days and 45% at 30 days, as pointed out in the accompanying editorial [3], and consistent with this high rate of treatment failure is a remarkably short time to next exacerbation of less than 1 month [1]. Since the percentage of patients treated with antibiotics in both study groups was very low (31% and 46%), it would be necessary to rule out that the reduction in the use of antibiotics is not responsible for an increase in clinical failures in this population with severe exacerbations of COPD. For comparison, a recent study using CRP to guide antibiotic use in much milder COPD patients in an ambulatory setting resulted in 57% of patients treated with antibiotics [4], in contrast to the 31% antibiotic prescription in CRP guided therapy in severe hospitalised patients in the study by Prins et al. [1].
Interestingly, the main outcome in the study by Prins et al. [1] is not a clinical outcome, but the reduction in the use of antibiotics with the CRP strategy compared to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy. This would be appropriate if both strategies for reduction of antibiotic use in admitted COPD patients would have been fully validated for efficacy and safety. However, there is no information in the article about the comparison of failure rates of patients taking or not taking antibiotics as a result of the application of either strategy. This information is crucial for the interpretation of the results, because it is very easy to restrict the use of antibiotics to patients with a CRP >50 mg·L−1, but it must be demonstrated that hospitalised patients not taking antibiotics due to a CRP <50 mg·L−1 are not at increased risk of failure due to this decision.
In order to have a complete understanding of the results and the clinical implications of their interesting study it would be necessary to have information about the clinical outcomes (30-day treatment failure, time to the next exacerbation and length of stay) in patients in whom antibiotics were prescribed compared to those not taking antibiotics in both study groups. This information would better clarify whether the desirable reduction of antibiotic use observed in the CRP-guided group was associated or not with an increased risk of clinical failure.
Antibiotics have differential effects on clinical outcomes based on their pharmacodynamic/pharmacokinetic properties. In severe exacerbations, antibiotic resistant pathogens such as Pseudomonas aeruginosa are common. There is no information provided whether amoxicillin/clavulanate, the primary antibiotic of choice in this study provided adequate coverage of the pathogens isolated from sputum in the participants. Bacteriological eradication of pathogens at exacerbation has been associated with clinical outcomes [5]. It is possible that inadequate antibiotic therapy was responsible for poor clinical outcomes in the antibiotic arms in this study.
It has been demonstrated that nearly 60% of patients with ambulatory exacerbations of mild-to-moderate COPD can be cured without antibiotics [6, 7], which means that we have substantial room for improvement in antibiotic prescription in this population. Furthermore, a series of variables, including CRP, may be useful to identify patients with exacerbations who can be safely treated without antibiotics in an ambulatory setting [4, 8]. These data indicate that a drastic reduction of antibiotic use is possible and needed in the outpatient setting, in which exacerbations are usually milder and self-limiting, and a significant number can be non-infective. However, we must be much more careful in reducing the use of antibiotics in severe exacerbations, which are associated with a poor short- and long-term prognosis if not adequately treated [9, 10].
Prins et al. [1] suggest that CRP-guided antibiotic therapy is able to reduce antimicrobial pressure while maintaining patient safety. This is true for the comparison between this strategy and the GOLD strategy. However, patient safety should be demonstrated by comparing the outcomes of patients with and without antibiotics as a result of the application of the CRP strategy. Having this additional information would better help clinicians to understand if the CRP-guided strategy may be a good instrument to safely reduce antimicrobial use in admitted patients with exacerbations of COPD.
Shareable PDF
Supplementary Material
This one-page PDF can be shared freely online.
Shareable PDF ERJ-01405-2019.Shareable
Footnotes
Conflict of interest: M. Miravitlles reports personal fees for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Zambon, CSL Behring, Grifols and Novartis, personal fees for consultancy from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, pH Pharma, Novartis and Grifols, grants from GlaxoSmithKline and Grifols, outside the submitted work.
Conflict of interest: C. Llor reports grants from Abbott Diagnostics, outside the submitted work.
Conflict of interest: L. Bjerrum has nothing to disclose.
Conflict of interest: S. Sethi reports grants and personal fees from GlaxoSmithKline and AstraZeneca, personal fees from Boehringer Ingelheim, Bayer, Aradigm, Sunovion and Theravance, outside the submitted work.
Conflict of interest: A. Anzueto reports personal fees for consultancy from GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim, outside the submitted work.
- Received July 15, 2019.
- Accepted July 20, 2019.
- Copyright ©ERS 2019