Damian McNamara

May 15, 2016

SAN FRANCISCO — Doxycycline added to oral corticosteroids for an acute exacerbation of chronic obstructive pulmonary disease (COPD) does not extend the time to next exacerbation, a randomized, double-blind, multicenter trial with a follow-up of 2 years reveals.

The researchers proposed doxycycline would have a positive effect. However, "the overall message is that antibiotics are not necessary for mild-to-moderate exacerbations of COPD without fever," Patricia van Velzen, MD, from the Academic Medical Centre in Amsterdam, the Netherlands, told Medscape Medical News.

Despite the negative findings, the results address some conflicting evidence in the literature and carry important implications for reducing antibiotic resistance, Dr van Velzen explained here at the American Thoracic Society (ATS) 2016 International Conference.

As part of the TEXACOLD trial, Dr van Velzen and colleagues assessed 301 patients with a COPD exacerbation receiving 30 mg oral corticosteroids for 10 days and randomly assigned them to either 7 days of doxycycline or placebo.

In addition to time to next exacerbation, they compared treatment failure and mortality rates. Patients with fever were excluded. Patients had a median age of 66 years, a forced expiratory volume in 1 second (FEV1) of 30% or greater after bronchodilation and FEV1/forced vital capacity less than or equal to 0.7 at baseline.

Severity of COPD and history of exacerbation did not alter the negative findings, Dr van Velzen added.

In terms of other clinical relevance, "Antibiotic resistance is a major clinical problem, and reducing antibiotic use is the most important strategy to contain resistance rates."

Table. TEXACOLD Trial Results for Patients With COPD Receiving Corticosteroids

Outcome Doxycycline Placebo P Value Hazard Ratio
Time to next exacerbation (days) 148 161 <1.26 1.03
Treatment failure at 21 days (%) 21 30 =0.07
Mortality over 2 years (n) 10 8 1.26

A previous Cochrane Database Systemic Review showed that antibiotics for COPD provide a consistent benefit for patients admitted to an intensive care unit. However, the results were inconsistent for other inpatients and outpatients ( Cochrane Database Syst Rev. 2012 Dec 12).

"The question here is how generalizable the results of the study to the whole group of patients with mild to severe COPD are," said Carl Llor, MD, from Universitat Rovira i Virgili in Tarragona, Spain, when asked by Medscape Medical News to comment.

 
Antibiotic resistance is a major clinical problem, and reducing antibiotic use is the most important strategy to contain resistance rates. Dr Patricia van Velzen
 

Dr Llor pointed out the investigators excluded patients with fever, which he and colleagues included in a previous report supporting the longer-term benefits of antibiotic therapy ( Am J Respir Crit Care Med. 2012;186:716-723).

Choice of antibiotic might also make a difference, Dr Llor said. "We used amoxicillin and clavulanic acid in our study — we know that amoxicillin and clavulanic acid has more lung penetration than doxycycline."

Regarding treatment failure at day 21, "the differences were not statistically significant, but in my opinion, this difference is clinically relevant. With the use of a more effective antibiotic, we did observe a failure of 9.5% at day 20." Dr Llor said. He added that his 2012 study did not include patients with severe COPD.

Session moderator Sanjay Sethi, MD, from the State University of New York at Buffalo, asked Dr van Velzen why she did not choose an antibiotic that showed benefit in a previous trial or a newer fluoroquinolones.

"We chose doxycycline because most COPD exacerbations are sensitive to doxycycline, and it is generally well-tolerated," she explained. "It's a first-choice antibiotic for treating outpatients in the Netherlands."

Dr Sethi said, "I think to project this to all antibiotics may not be the right thing based on other data."

Dr van Velzen, Dr Llor, and Dr Sethi have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2016 International Conference: Abstract 1021. Presented May 15, 2016.

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