A sputum culture does not need to be routinely sent in patients with COPD exacerbations but should be considered in patients with severe underlying disease or those hospitalized for COPD exacerbations with purulent sputum or requiring ventilatory support.

A 2007 prospective study¹ of 40 hospitalized patients compared sputum sample against bronchoscopic protected specimen brush (PSB), the gold standard for detecting distal airway infections, for isolation of bacterial pathogens in COPD exacerbations. All patients had a spirometric diagnosis of COPD and recent pulmonary function testing. Patients with pneumonia and recent antibiotic use were
excluded. Sputum samples and PSBs were collected within 24 hours of admission.

There was strong agreement between sputum and PSB culture results (κ = 0.85; P < .002). Patient-reported sputum purulence was strongly predictive of potentially pathogenic bacteria on PSB (OR 27.20, 95% CI 4.60-60.69; P = .001). Other predictive factors of PSB culture positivity were FEV1 <50% (OR 2.27, 95% CI 1.55-3.21; P = .01), >4 exacerbations in the past year (OR 6.91, 95% CI 1.24-38.52; P = .03), and hospitalization in the past 3 years (OR 4.13, 95% CI 1.02-16.67; P = .04). The overall sensitivity and specificity of sputum purulence for predicting PSB positivity were 89.5% and 76.5%, respectively. Generalizability is limited by the study’s small size, inclusion of only men, and skew toward patients with more significant disease (the mean FEV1 of patients was 37% and >50% of patients reported >4 exacerbations per year). Additionally, while bronchoscopy is the gold standard for diagnosis of pneumonia, the authors used a threshold of ≥10² cfu/mL, which is lower than the accepted threshold for bacterial infection²,³ and may not adequately distinguish between colonization and infection.

Current guidelines recommend sputum analysis for patients with a COPD exacerbation and high likelihood of bacterial infection.⁴,⁵ The 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend cultures in patients with frequent exacerbations, severe airflow limitation, or exacerbations requiring mechanical ventilation. The 2010 National Institute for Health and Clinical Excellence (NICE) guidelines recommend sputum microscopy and culture in all hospitalized patients with purulent sputum (grade D, based on expert opinion).

Antibiotics should be given to all patients requiring ventilatory support as well as those with sputum purulence and at least one additional cardinal symptom of COPD exacerbation.

Older studies of largely chronic bronchitis patients demonstrated that those with three cardinal symptoms of COPD exacerbation—increased sputum volume, sputum purulence, and dyspnea—benefited from antibiotics, in contrast to those with only one symptom.⁴,⁶
However, concerns about antibiotic resistance and adverse effects have compelled closer inspection of routine antibiotic use.

A meta-analysis reviewed 16 randomized controlled trials (RCTs) comparing antibiotics versus placebo in COPD exacerbations.⁶ All trials included patients with a clinical or spirometric diagnosis of COPD and excluded patients with pneumonia. In treatment groups, antibiotics were administered for ≥2 days, with specific antibiotics including commonly used (e.g., amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, doxycycline) and less common (e.g., chloramphenicol, tetracycline, streptomycin) agents. Notably, the most commonly used antibiotics, azithromycin and fluoroquinolones, were not studied in the trials included in this meta-analysis. The primary outcome was treatment failure through 4 weeks (defined as no resolution or deterioration of symptoms, death, or need for additional antibiotics during this period). Four trials exclusively evaluated patients hospitalized with COPD exacerbations on the wards and demonstrated that antibiotics reduced the risk of treatment failure up to 4 weeks (RR = 0.77, 95% CI 0.65-0.91; P = .002; number needed to treat [NNT] = 10). Secondary outcomes of all-cause mortality and length of stay did not differ significantly between antibiotic and placebo groups. In contrast, among ICU patients, anti-biotics were associated with decreased mortality (Peto OR = 0.21, 95% CI 0.06-0.72; P = .01; NNT = 6) and length of stay (mean difference -9.60 days, 95% CI −12.84 to −6.36 days, P-value not reported).