Chronic obstructive pulmonary disease (COPD) is a complex amalgam of lung diseases, associated with alveolar destruction, inflammation, mucus production, and airway obstruction. The Center for Disease Control and Prevention (CDC) estimates that approximately 16 million people suffer from COPD in the United States. Several studies have shown that each year one-half of COPD sufferers will experience at least one COPD exacerbation. This typically involves increased debility, sometimes involving hospitalization, steroid therapy, and a course of antibiotics.
Although pulmonary infection is the leading cause of COPD exacerbation, it is not present in every case, and in cases that are due to infection, many are viral in origin. Thus, antibiotic stewardship has been an ongoing challenge in the treatment of COPD exacerbation. Point-of-care tests, such as CRP, are being sought to help safely decrease antibiotic use where they not only provide no benefits, but contribute to increased costs, adverse drug effects, and antimicrobial resistance.
Christopher C. Butler, F. Med. Sci., with the Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom, and colleagues reported their findings in the July 11, 2019 issue of The New England Journal of Medicine.
The trial is called the PACE study (Point of care testing to target antibiotics for chronic obstructive pulmonary disease exacerbations). It is a multicenter, open-label, randomized, controlled trial involving 86 general medical practices in the United Kingdom. They randomized 653 COPD patients presenting with a COPD exacerbation to either usual care, or care guided by point-of-care CRP testing. Guidance was given to the treating clinicians as follows: patients who had a CRP level below 20 mg per liter were unlikely to benefit from antibiotic therapy, those who had a CRP level above 40 mg per liter were likely to benefit from antibiotic therapy, and those with a CRP level between 20 and 40 mg per liter may benefit from antibiotic therapy, especially if those patients were reporting purulent sputum production. Patient-reported antibiotic use within four weeks after randomization was compared between groups.
Patient-reported antibiotic use was lower in the CRP-guided care group than in the usual-care group (57% and 77.4% respectively, a 20.4% between-group difference; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47).
There was no significant difference in the rate of adverse events reported between the groups. In the four-week follow-up period two patients in the usual-care group died, one from pneumonia and one from respiratory failure, but the trial investigators deemed these events unrelated to the trial.
The study was funded by the National Institute for Health Research Health Technology Assessment Program.
Butler CC, Gillespie D, White, P, et al. C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations. N Engl J Med. 2019; 381:111-20.
Comments
The importance of this study, and others like it, cannot be overstated in that they address one of the most critical issues in medicine today: antibiotic stewardship. The pressure on clinicians to prescribe antibiotics for any of a wide range of symptoms is immense. It is well understood that antibiotics are critical and lifesaving when properly used – however, the CDC reports that 30-50% of antibiotics prescribed in both the outpatient and hospital settings are not necessary. The increasing number of multi-drug resistant bacteria and antibiotic-associated adverse events, such as Clostridium difficile colitis, greatly incentivize decreasing antimicrobial overuse. This study is good evidence that a point-of-care test can actually improve clinical decisions regarding the use of antibiotics.
NB: In spite of the much-needed attention being placed on these issues, and studies like this which are helping clinicians make good antibiotic prescription choices, it is important to realize that a significant amount of antibiotics are also used in animal agriculture and industrial farming. The exact amount or the percentage relative to what is used in humans is difficult to define (some reports state as much as 70-80% of ALL antibiotic use in the U.S. is in the farming industry). What is clear is that we continue to ignore the warning of Alexander Fleming at our peril – the discoverer of penicillin stated in a 1945 interview how the misuse of antibiotics would most certainly lead to the development of resistant bacteria.