Maybe not for one subgroup of patients, says study from Germany

The need for antibiotics in patients with chronic obstructive pulmonary disease (COPD) seeking treatment for moderate acute COPD exacerbations could not be ruled out in a randomized trial from Germany, except perhaps for one subgroup.

In the ABACOPD study of nearly 300 patients, the overall treatment failure rate among those receiving 5 days of sultamicillin was 15.3%, as compared to 25.0% for those who received placebo, falling outside the bounds of non-inferiority (9.97% between group difference, 95% CI 0.7-19.23), reported Gernot Rohde, MD, of Frankfurt University Hospital in Germany.

But in the subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 or 2 patients, the failure rate — need for antibiotics during the treatment period or ahead of a test-of-cure visit at day 30 — was twice as high with the antibiotic (29.82% vs 14.29%).

“The trial failed to demonstrate that antibiotics [are] not needed for patients with acute moderate exacerbation of COPD across all stages of the disease,” Rohde said during a presentation at the European Respiratory Society annual meeting. “But we are very confident that at least we can say that this treatment is unnecessary in GOLD stages 1/2, and we have to say it cannot be withheld in GOLD stages 3/4.”

The role of antibiotics in treating COPD is debated, Rohde explained, as a large proportion of exacerbations are associated with viral infections. According to the AERIS study, as little as 37.7% of medical visits for COPD exacerbations were positive for bacterial infection on PCR testing.

But the reality, at least in German emergency rooms, said Rohde, is that most patients will arrive having already received antibiotics prescribed by general practitioners. This and recent hospitalizations were the reasons behind most of the exclusions in the present study.

From 2013 to 2019, the double-blind, multicenter ABACOPD trial randomized 294 patients presenting at 28 different sites in Germany to either 5 days of sultamicillin of placebo. Most (70%) of the patients were treated in the hospital setting while the remaining were outpatients. All participants received standard care, including 40 mg of prednisone for 7 to 10 days, oxygen if needed, and continuation of inhaled therapy.

Baseline characteristics were similar between groups. The average patient age was 66.5 years, and 62% were men. A third of the patients had GOLD stages 1 or 2 disease while the remaining had GOLD stage 3 or 4 disease. A majority (60.5%) reported having exacerbations in the prior year, and 58% were current smokers. Nearly all patients were on bronchodilators and about half were on concomitant corticosteroids.

The proportion of patients reporting at least one adverse event (AE) was higher in the antibiotic group compared with the placebo group (53% vs 42%, P=0.0453), said Rohde, though no differences were seen for serious AEs.

Patients were required to have moderate acute exacerbation of COPD but without respiratory failure or need for intermediate or intensive care. Other inclusion criteria were: age over 40, having a smoking history of 10 pack-years or more, the absence of community-acquired pneumonia or respiratory tract infection with a clear indication for antibiotics, and the absence of pulmonary infiltrates.

Patients were excluded if they had fever, impaired hepatic or renal function, tuberculosis, a methicillin-resistant Staphylococcus aureus (MRSA) infection, known bronchiectasis, an acute asthma exacerbation, or hypersensitivity or suspected serious adverse reaction to sultamicillin. Other exclusion criteria were antibiotic use within the last 30 days and use of immunosuppression therapies.