Antibiotic use may not be necessary in COPD patients with nonpurulent exacerbation

Treatment without antibiotic medication does not appear to be inferior to moxifloxacin therapy as regards treatment failure or length of stay (LOS) among patients with chronic obstructive pulmonary disease (COPD) requiring hospitalization for nonpurulent exacerbation, according to the results of a study presented at the European Respiratory Society (ERS) International Congress 2019.

“The noncontrolled use of antibiotics in acute exacerbation of COPD results in a very expensive disease and raises the rate of resistance of bacteria,” said Nestor Soler Porcar, one of the principal authors of the study. [https://clinicaltrials.gov/ct2/show/NCT01091493]

Of the 287 COPD patients diagnosed with nonpurulent exacerbation, 73 were randomly assigned 1:1 to a 5-day course of oral moxifloxacin (400 mg daily) or placebo. Seventy-two patients were then included in the intention-to-treat analysis (37 in the moxifloxacin arm and 35 in the placebo arm).

Treatment failure rate on day 3 was the primary outcome. A noninferiority margin with a failure limit of 15 percent was assumed.

Treatment failure occurred in three patients (8 percent) in the moxifloxacin arm and four patients (11 percent) in the placebo arm (difference, 3 percent, two-sided 95 percent CI, –0.10 to 0.17; p=0.71), not reaching the prespecified noninferiority failure limit of 15 percent. [Huerta A, et al, ERS 2019]

No significant between-group differences were observed in terms of LOS (median, 6 days; interquartile range [IQR], 4–7 in placebo arm vs 5 days [IQR, 4–7] in moxifloxacin arm).

“Previous data from our group showed that sputum purulence-guided antibiotic treatment strategy might be useful in severe exacerbations,” the investigators said. [Thorax 2007;62:29-35; Eur Respir J 2012;40:1344-1353]

A 2017 review providing an update on antibiotic treatment of exacerbation of COPD reported no beneficial effect of antibiotics in patients who do not need hospital admission and do not present with purulent sputum nor increased levels of C-reactive protein/procalcitonin. [Ugeskr Laeger 2017;10:179]

On the other hand, the researchers recommended antibiotics for those with severe COPD and increased sputum purulence, with amoxicillin as first-line treatment, as it is effective against the most common types of bacteria in COPD exacerbation. Amoxicillin/clavulanate may also be used as first-line treatment in patients with very severe COPD. [Ugeskr Laeger 2017;10:179]

Furthermore, a study by Stolz and colleagues from way back in 2007, which included 208 consecutive patients requiring hospitalization for COPD exacerbation, found that procalcitonin guidance “offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3.” [Chest 2007;131:9-19]

In a retrospective analysis by Bathoorn and colleagues, they found that guidelines regarding antibiotics prescription were poorly followed, particularly in recurrent exacerbations. Sputum cultures were also performed only in a small minority of cases. [Int J Chron Obstruct Pulmon Dis 2017;12:285-290]

“Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment,” according to Bathoorn and colleagues.