COPD Managed With Long-term Antibiotic Prophylaxis

An Expert Interview With Trish Orlando, PharmD

Steven Fox

November 15, 2012

Editor's note: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world and the third leading cause of death in the United States. About 24 million Americans share that diagnosis.

One strategy being used to prevent exacerbations of COPD, with some success, is long-term antibiotic prophylaxis.

At the American College of Clinical Pharmacy (ACCP) 2012 Annual Meeting, held October 21 to 24 in Hollywood, Florida, Trish Orlando, PharmD, FCCP, presented a special session focusing on that approach to management.

Dr. Orlando is associate professor of pharmacotherapy at the University of Utah College of Pharmacy in Salt Lake City. She also serves as an infectious diseases pharmacist at the George Wahlen Veterans Affairs Medical Center in Salt Lake City.

In an email interview with Medscape Medical News, Dr. Orlando discussed the prophylactic management of COPD.

Medscape: Can you describe the toll COPD takes in terms of patient morbidity and mortality?

Dr. Orlando: COPD causes a significant healthcare burden for millions of patients with that primary diagnosis. More than half of these patients report significant impairment in the ordinary activities of daily living, with reduced productivity. Over 726,000 hospital admissions are due to COPD each year, resulting in $29.5 billion in direct healthcare medical expenditures and roughly $20 billion in indirect morbidity/mortality costs.

Medscape: Is the cause of COPD flare-ups more often bacterial or viral?

Dr. Orlando: Approximately half of COPD exacerbations may be due to bacterial infection. COPD patients are commonly colonized with bacteria. Clinically significant bacterial sputum concentrations have been noted in at least 54% of patients with COPD exacerbations. Common offenders include Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarhallis, and Pseudomonas aeruginosa (which may be more important in advanced stages of COPD).

Medscape: What are the traditional methods used to prevent exacerbations of COPD?

Dr. Orlando: Current methods to prevent exacerbations of COPD include smoking-cessation programs, vaccination programs (especially pneumococcal and annual influenza vaccinations), anticholinergic therapy, long-acting beta agonists with or without inhaled steroids, pulmonary rehabilitation programs, exercise programs, and avoidance of offending environmental factors (such as poor quality air).

Medscape: Is the use of prophylactic antibiotics to prevent COPD exacerbations a new approach?

Dr. Orlando: The use of prophylactic antibiotics for the prevention of COPD exacerbations was tried several decades ago; the primary aim was to reduce the bacterial burden that was thought to be responsible for the exacerbations.

However, until recently, antibiotics haven't been widely used [for this purpose]. Although older studies found a small but statistically significant effect in reducing the number of sick days, with small insignificant reductions in the overall exacerbation rate, adverse drug reactions were common, and practitioners had concerns about the impact on antibiotic resistance.

However, antibiotic prophylaxis is making a resurgence as a therapeutic option. It is primarily aimed at reducing patient morbidity associated with COPD exacerbations and cutting down on hospitalizations.

Medscape: Which drugs are used most often, and what are the most effective routes of administration?

Dr. Orlando: The prophylactic role of oral macrolides (erythromycin, clarithromycin, azithromycin) and respiratory quinolones (mainly moxifloxacin) has been studied in COPD exacerbations. The oral route has been seen frequently in studies using the daily administration of macrolides. Oral therapies involving pulsed azithromycin 3 times per week have been studied over the course of a year in a small group of patients. Prophylactic inhalation therapies for COPD exacerbations require more study since the available data have evolved from cystic fibrosis inhalation trials.

The most recognized study [by Richard K. Albert and colleagues; N Engl J Med. 2011;365:689-698] identified an extended remission time between exacerbations, an overall reduction in exacerbation frequency, and improved St. George's Respiratory Questionnaire scores in patients who received daily azithromycin during the trial. Hearing deficits were noted in 25% of patients who received azithromycin and in 20% of patients who received placebo [< .04].

Also, the prevalence of resistance to macrolides was 52% at study entrance. Of the 68% of patients [randomized to azithromycin] who were not colonized at enrollment, [81%] developed resistance during the study period. [Compare this with 70% of those randomized to placebo who were not colonized at the time of enrollment; only 41% of those participants developed resistance during the study period; < .001.]

Medscape: What are the contraindications for long-term antibiotic prophylaxis? In which patients should such an approach be avoided?

Dr. Orlando: Any time long-term antibiotics are used in a patient's regimen, the practitioner has to be concerned about potential drug interactions. Of course, that is a potential concern when any new drug is added to a patient's regimen.

Long-term antibiotic prophylaxis can potentially lead to the emergence of bacterial resistance. It's important to reassess the utility of such programs on a scheduled basis, both from a bacterial and a general clinical standpoint. Making sure that is done helps protect patients from potential side effects and resistance issues.

Medscape: What are the main issues practitioners should consider when deciding whether to prescribe antibiotic prophylaxis?

Dr. Orlando: The biggest issue to consider is what phenotype you are dealing with, and whether the antibiotic you are planning to use is likely to be active against that organism. More studies are needed to sort out such questions. In the meantime, practitioners need to individualize approaches to care for each patient.

Concerns about adverse events and bacterial resistance issues continue to be important considerations when making these decisions.

Dr. Orlando has disclosed no relevant financial relationships.

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