By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Point-of-care C-reactive protein testing can safely and effectively reduce antibiotic use in patients with acute exacerbations of chronic obstructive lung disease.

SOURCE: Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111-120.

Butler and colleagues examined the value of point-of-care C-reactive protein (CRP) testing to guide the need for antibiotic therapy in patients > 40 years of age with exacerbations of chronic obstructive pulmonary disease (COPD). To this end, they performed a randomized, open-label, controlled trial at 86 general practices in the United Kingdom. An exacerbation was defined as the presence of at least one of the widely used Anthonisen criteria: increased breathlessness, increased sputum volume, or increased sputum purulence. Subjects were randomized to usual care alone or usual care guided by CRP testing.

Participating clinicians received guidance for the interpretation of CRP results, indicating that antibiotic therapy was unlikely to be beneficial and ordinarily should not be prescribed if the value was < 20 mg/L, that it was likely to be beneficial if CRP was > 40 mg/L, and that it may be beneficial for those with intermediate levels, particularly if purulent sputum is present. The clinicians also were told that general clinical factors should be taken into account in decisions about antibiotic use.

The median CRP in the 317 patients randomized to the usual care plus CRP group and in whom the test was performed was 6 mg//L, with 241 (76.0%) < 20 mg/L, 38 (12.0%) were 20-40 mg/L, and 38 (12.0%) were > 40 mg/L. At the initial consultation, antibiotics were prescribed to 47.7% and 69.7% in the CRP-guided and usual care alone groups, respectively (adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.21-0.45). Overall antibiotic use in the four weeks after randomization (a co-primary endpoint) was reported by 57.0% in the CRP group, while it was 77.4% in the usual care group (adjusted odds ratio, 0.31; 95% CI, 0.20-0.47). At two weeks, the adjusted mean difference in the Clinical COPD Questionnaire score was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the group guided by CRP testing, demonstrating, at a minimum, a lack of harm from this strategy.

COMMENTARY

Given the frequency of COPD occurrence, it is somewhat disturbing that our knowledge of the role of antibiotics in the management of exacerbations seems so limited and confused. As stated in Murray and Nadel’s Textbook of Respiratory Medicine, “The use of antibiotics for exacerbations of COPD is somewhat controversial.”

A recent Cochrane review, while agreeing that antibiotics are beneficial in patients who require intensive care admission, concluded that the effects of antibiotic therapy on other inpatients and on outpatients are small and “inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay).”1

In previous studies, researchers have examined the use of procalcitonin measurements in these exacerbations. Thus, a meta-analysis concluded that although the quality of the available evidence was only low to moderate due to methodological limitations and small populations, the use of procalcitonin-based protocols was associated with reduced antibiotic use.2 On the other hand, a retrospective study of 203,177 patients hospitalized for management of COPD exacerbations concluded that procalcitonin measurement had little effect on decisions to initiate antibiotic therapy.3 Researchers also have studied the use of a comprehensive viral respiratory panel for which there is evidence of potential benefit.4

The study by Butler and colleagues is welcome in shedding a light on this subject. Their work demonstrates that point-of-care CRP testing can be used effectively and safely to reduce antibiotic use in patients with acute exacerbations of COPD. Further exploration of predictors of antibiotic benefit and work aimed at improving prescribers’ behavior must follow. The issue of the importance of altering prescriber behavior is evident in the study by Butler et al since almost half of patients with low CRP levels nonetheless received prescriptions for antibiotic therapy.

REFERENCES

  1. Vollenweider DJ, Frei A, Steurer-Stey CA, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2018;10:CD010257.
  2. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, Vestbo J. Procalcitonin to guide antibiotic administration in COPD exacerbations: A meta-analysis. Eur Respir Rev 2017;26. doi: 10.1183/16000617.0073-2016.
  3. Lindenauer PK, Shieh MS, Stefan MS, et al. Hospital procalcitonin testing and antibiotic treatment of patients admitted for chronic obstructive pulmonary disease exacerbation. Ann Am Thorac Soc 2017;14:1779-1785.
  4. Tickoo M, Ruthazer R, Bardia A, et al. The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: A retrospective before-after study. BMC Pulm Med 2019;19:118.