Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

The answer is “NO”! With an estimated 20% to 50% of acute chronic obstructive pulmonary disease (COPD) exacerbations attributed to noninfectious factors (1,2), routine inclusion of antibiotics in the treatment of this condition is not only unnecessary but potentially harmful.

 
Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommends the use of antibiotics in patients who have dyspnea, increased sputum volume, and increased sputum purulence—or at least 2 of these 3 criteria when sputum purulence is one of them (3)—, these recommendations are not based on robust evidence and have not been widely corroborated (2,4-6).

 
That’s why the findings of a 2019 New England Journal of Medicine study (PACE) supporting the use of serum C-reactive protein (CRP) as an adjunctive test in COPD exacerbation is particularly welcome (1). In this multicenter randomized controlled trial performed in the U.K., the following CRP guidelines (arrived from prior studies) were provided to primary care clinicians to be used as part of their decision making in determining which patients with COPD exacerbation may not need antibiotic therapy:

 
• CRP less than 20 mg/L: Antibiotics unlikely to be beneficial
• CRP 20-40 mg/L: Antibiotics may be beneficial, mainly if purulent sputum is present
• CRP greater than 40 mg/L: Antibiotics likely to be beneficial

 
Adoption of these guidelines resulted in significantlly fewer patients being placed on antibiotics without evidence of harm over a 4-week follow-up period (1).  Despite its inherent limitations (eg, single country, outpatient setting), CRP testing may be a step in the right direction in curbing unnecessary use of antibiotics in COPD exacerbation.  

 

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References

 
1. 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. https://www.ncbi.nlm.nih.gov/pubmed/31291514
2. Llor C, Moragas A, Hernandez S, et al. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:716-23. https://www.ncbi.nlm.nih.gov/pubmed/22923662
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019 (http://www.goldcopd.org).
4. Brett AS, Al-Hasan MN. COPD exacerbations—A target for antibiotic stewardship. N Engl J Med 2018;381:174-75. https://www.ncbi.nlm.nih.gov/pubmed/31291521
5. Miravitlles M, Moragas A, Hernandez S, et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013;144:1571-7. https://www.ncbi.nlm.nih.gov/pubmed/23807094
6. Van Vezen P, Ter Riet G, Bresser P, et al. Doxycycline for outpatient-treated acute exacerbations of COPD: a randomized double-blind placebo-controlled trial. Lancet Respir Med 2017;5:492-9. https://www.ncbi.nlm.nih.gov/pubmed/28483402

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

How well does procalcitonin distinguish bacterial from viral causes of community-acquired pneumonia in hospitalized patients?

Not extremely well! Although a recent multicenter prospective study in adult hospitalized patients reported that the median procalcitonin (PCT) concentration was significantly lower for community-acquired pneumonia (CAP) caused by viral pathogens ( 0.09 u/ml vs atypical bacteria [0.2 ug/ml] and typical bacteria [2.5 ug/ml]),  PCT was <0.1 ug/ml and <0.25 ug/ml  in 12.4% and 23.1% of typical bacterial cases, respectively1

This means that we could potentially miss about a quarter of CAP cases due to typical bacterial causes if we use the <0.25 ug/ml threshold (<0.20 is ug/ml has been used to exclude sepsis2). For these reasons and based on the results from another study3, no threshold for PCT can reliably distinguish bacterial from viral etiologies of CAP4.  Clinical context is essential in interpreting PCT levels! Also go to a related pearl on this site5.

Can PCT distinguish Legionella from other atypical bacterial causes of CAP (eg, caused by Mycoplasma or Chlamydophila)? The answer is “maybe”! Legionella was associated with higher PCT levels compared to  Mycoplasma and Chlamydophila in one study1, but not in another3.

References

  1. Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017;65:183-90. https://www.ncbi.nlm.nih.gov/pubmed/28407054
  2. Meisner M. Update on procalcitonin measurements. Ann Lab Med 2014;34:263-73.
  3. Krüger S, Ewig S, Papassotiriou J, et al. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP-Results from the German competence network CAPNETZ. Resp Res 2009;10:65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714042/pdf/1465-9921-10-65.pdf
  4. Bergin SP, Tsalik EL. Procalcitonin: the right answer but to which question? Clin Infect Dis 2017; 65:191-93. https://academic.oup.com/cid/article-abstract/65/2/191/3605416/Procalcitonin-The-Right-Answer-but-to-Which?redirectedFrom=fulltext
  5. https://pearls4peers.com/2017/07/01/should-i-order-serum-procalcitonin-on-my-patient-with-suspected-infection    
How well does procalcitonin distinguish bacterial from viral causes of community-acquired pneumonia in hospitalized patients?

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?

 

Discordance between serum CRP and ESR is not uncommon (1,2). This phenomenon may be due to a variety of factors including the fact that the kinetics of these two tests is quite different, as discussed under “Should I order C-reactive protein (CRP) or erythrocyte sedimentation (ESR) on patients suspected of having a new infection?” in this blog.

In a study of CRP/ESR discordance (defined as results differing by 2 or 3 quartiles) in adults, a high CRP/low ESR profile was more likely to be associated with  urinary, GI, blood stream, and pulmonary infections, myocardial infarction, and venous thromboembolism and less likely to be associated with bone and joint infections (1).

In the same study, a high ESR/low CRP was associated with connective tissue diseases, such as systemic lupus erythematosus and strokes (1).

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References

1. Feldman M, Aziz B, Kang GN, et al. C-reactive protein and erythrocyte sedimentation rate discordance: frequency and causes in adults. Translational Research 2013;161:37-43. https://www.ncbi.nlm.nih.gov/pubmed/22921838

2. Colombet I, Pouchot J, Kronz V. Agreement between erythrocyte sedimentation rate and C-reactive protein in hospital practice. Am J Med 2010;123:864.e7-863.e13.https://www.ncbi.nlm.nih.gov/pubmed/20800157

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?