Cystic fibrosis (CF) is an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the United States, according to the CF Foundation. Although the disease affects many organs, 85% of deaths in CF results from lung disease. CF is associated with progressive decline of lung function. Episodes of acute worsening of respiratory symptoms—or pulmonary exacerbations—frequently occur, and there are various clinical features associated with exacerbations (Table 1). “Pulmonary exacerbations have an adverse impact on patients’ quality of life and overall cost of care,” says Patrick A. Flume, MD. “They’re also the most common reason for hospitalization of CF patients. Identifying optimal treatment methods for pulmonary exacerbations in CF could lead to significant improvements in quality and length of life for patients living with the disease.”

In the November 1, 2009 American Journal of Respiratory and Critical Care Medicine and available for free online at, guidelines for the treatment of pulmonary exacerbations in CF were published. Dr. Flume and members of the CF Foundation’s Pulmonary Therapies Committee collaborated to evaluate published results of controlled trials of common treatment methods for exacerbations in an effort to identify best treatment practices. “The intent of this research was to evaluate the evidence supporting therapies and approaches for the management of health decline,” says Dr. Flume. “Our systematic review allowed the committee to make specific treatment recommendations [Table 2] as well as determine areas that require further study. The guidelines are designed for general use in most patients with CF, but they should be adapted to meet specific needs as determined by the patient, their family, and their healthcare provider. This is the first comprehensive and evidence-based systematic review of best practices for pulmonary exacerbation of CF.”

Where Should Patients Be Treated?

Once a decision has been made to intervene for pulmonary exacerbations, the clinician must decide where that treatment can best be provided. IV antibiotic therapy is an effective component of treatment for pulmonary exacerbations, and many patients have been treated at home. “The research indicates that home therapy may be appropriate for selected patients with CF, but evidence is limited,” says Dr. Flume. “In cases where outpatient resources cannot match inpatient resources, there is no reason to expect similar outcomes. If there are any doubts, admission to hospitals is recommended, especially if patients have comorbidities that may complicate care or if exacerbations are more severe.”

Continue Chronic Therapies to Maintain Lung Health

Recommendations for using chronic medications and airway clearance therapies remained consistent with prior guidelines for treating CF. “We found no compelling reason why any recommended chronic therapy should be discontinued during treatment of pulmonary exacerbations,” Dr. Flume says. The guideline also concluded that there was insufficient evidence to recommend for or against continued use of inhaled antibiotics in patients treated with the same antibiotics intravenously. Furthermore, airway clearance therapy should be continued as a part of treatment of acute exacerbations of pulmonary disease. Treatment of exacerbations should be looked upon as an opportune time to educate patients further about the various methods of airway clearance.

Using Antibiotics to Treat Pseudomonas aeruginosa

The most common pathogen identified in cultures of the CF airways is Pseudomonas aeruginosa. Antibiotic choices for treatment of acute exacerbations are typically directed at this pathogen. “Use of combination antibiotic therapy has not been validated in the treatment of CF lung infections, but the standard of care has been to use combination antibiotics to treat P. aeruginosa in patients with CF,” says Dr. Flume. “Ultimately, there isn’t enough compelling evidence to change that strategy.”

“Identifying optimal treatment methods for pulmonary exacerbations in CF could lead to significant improvements in quality and length of life.”

“Our goal was to codify the current status of intracranial endovascular cerebrovascular procedures,” says Dr. Meyers. “Currently, we are seeing tremendous interest in and proliferation of these endovascular techniques to treat cerebrovascular disease. This enthusiasm emanates from multiple medical specialties. This is partially due to the potential impact these procedures may have on important causes of disability and death, such as acute stroke. However, many of these techniques remain essentially experimental and require significantly more investigation before they become broadly applied to general medical practice. Consequently, many of these procedures still aren’t reimbursed or have circumscribed indications. For these reasons, a multidisciplinary committee is especially important to weigh the evidence until there is greater scientific proof.”

Considerations in Antibiotic Dosing

Aminoglycoside antibiotics are commonly used in the treatment of CF pulmonary exacerbations. The dosing of aminoglycosides, however, is limited by their potential for nephrotoxicity, ototoxicity, and vestibular toxicity. “Traditionally, these antibiotics have been dosed on a 3-times-daily schedule, but some investigations have suggested that once-daily dosing may be more beneficial,” Dr. Flume notes. After reviewing the efficacy of once-daily compared with multiple-dose daily aminoglycoside therapy for the treatment of an acute exacerbation of CF pulmonary disease, research demonstrated comparable efficacy for once-, twice-, and thrice-daily dosing of aminoglycosides. “Patients receiving frequent courses of aminoglycosides should be monitored periodically for drug concentration and toxicity assessments because dosage adjustment may be necessary,” adds Dr. Flume.

Other medications sometimes used to treat exacerbations in CF are β-lactam antibiotics. These agents have time-dependent pharmacodynamic properties, meaning it is preferable to maintain their concentration above the minimum inhibitory concentration for longer portions of the dosing interval. “The perception is that these antibiotics may have a better antibacterial effect,” explains Dr. Flume. “However, increasing the concentration above this point has not been shown to improve the killing effect of the antibiotic. As such, there has been interest in using continuous or extended infusion of β-lactam antibiotics. Unfortunately, there isn’t enough evidence yet to recommend this treatment approach.”

How Long Should Antibiotics Be Used?

The duration of antibiotic therapy has been studied in different patient groups with conditions or diseases other than CF, and they consistently support shorter durations of therapy. “We were unable to find a study that addressed this question in the treatment for acute exacerbations of CF pulmonary disease,” says Dr. Flume. “The optimal duration of antibiotic therapy, however, is an important question that should be studied further.” The guidelines recommend that key clinical endpoints in such trials include lung function, toxicity, selection of antibiotic-resistant pathogens, time to next exacerbation, and health-related quality of life.

Synergy Testing

Synergy testing assesses the effects different antibiotics have when used in combination against multidrug resistant infections. “The role for routine synergy testing in exacerbations of CF has been recently debated,” Dr. Flume says, “but our review of the research found that this testing appeared to have little benefit to patients. As such, we recommended against the use of synergy testing as part of the routine evaluation of acute exacerbations of pulmonary disease and multidrug-resistant bacteria. However, antibacterial synergism may be relevant in unique clinical settings, such as when patients are awaiting lung transplantation or in those with multiresistant pathogens who have failed to respond to antibiotics selected by standard means, but such strategies require more research.”

Corticosteroid Use Discouraged

The guidelines for chronic therapies to maintain lung function had recommended against the routine use of oral or inhaled corticosteroids when treating patients with CF. Corticosteroids can be beneficial for lung health, but the adverse effects of steroids were enough to show that the overall harm from side effects outweighs any benefits. However, it is not yet known whether there is benefit to a short course of steroids for the treatment of an acute pulmonary exacerbation. Larger, well-designed clinical trials are needed to determine the role of steroid treatment during acute exacerbations of pulmonary disease.

More to Come

Dr. Flume says that the recommendations created by the CF Foundation’s Pulmonary Therapies Committee should be viewed as a guideline for CF care. “It’s our intent to review these recommendations periodically to address new data. There are many important questions remaining for which we lack high-quality data and for which additional studies are needed. Hopefully, clinicians will find these recommendations useful in their current care of patients with CF and use these to generate more research in the future that addresses some of the unanswered questions that linger.”