ESSEN, GERMANY—Pseudomonas aeruginosa colonizes the airways of more than 80% of patients with cystic fibrosis (CF), reducing lung function and life expectancy. By initiating long-term inhaled tobramycin before the microbe could switch its phenotype, Felix Ratjen, MD, and colleagues eradicated the infection in 14 of 15 CF patients.[1]

Fifteen patients, ages 1 to 22 years, newly diagnosed with P aeruginosa infection, inhaled 80 mg tobramycin in 2 mL saline twice daily for one year. After treatment, negative throat swab cultures were obtained from all but one patient, in whom P aeruginosa infection was eradicated with an additional three-month course. One year after drug discontinuation, throat cultures from 14 of 15 patients remained pseudomonas-free, and all patients were seronegative at two-year follow-up. By contrast, seven of eight CF patients with P aeruginosa infection in a previous study remained infected after one year of placebo administration.

Asked whether the regimen’s success was attributable to long treatment duration or the high drug concentrations permitted with inhalation, Dr. Ratjen, a pediatrician at the University of Essen Children’s Hospital, told RESPIRATORY REVIEWS, “Probably both. After a treatment of three to six months, … there were still a few positive cultures.” But success “also depends on concentration,” he noted. “Inhaled therapy can give much higher concentrations” of antibiotic in the airways than can titers afforded by intravenous (IV) administration. However, he added, “No one has tried to do IV treatment for this extended period.”

Early in pseudomonal infection, “you first have colonization with small numbers of bacteria. After six months to a year, they then form a biofilm” and switch to an alternate mucoid phenotype, explained Dr. Ratjen. “As soon as it becomes mucoid, it has deleterious effects. The anaerobic conditions in CF biofilms seem to favor this switch to a mucoid phenotype.”

Mucoid aggregates are less vulnerable to antibiotics, so early treatment to block development of this phenotype may be crucial in avoiding chronic infection. For chronic lung infection with P aeruginosa, said Dr. Ratjen, “the usual treatment is a two- to three-week course of IV antibiotics. But if you do that, you suppress pseudomonas …, but you don’t really eradicate it.”

Although early treatment is essential to protect CF patients from chronic pseudomonal infection, “I don’t think prophylaxis would be … reasonable,” said Dr. Ratjen. “What is important is that you screen on a regular basis. If you don’t, you may miss it” when the infection is still vulnerable to antibiotics. “Given the success of the trial, we recommend looking at sputum or throat swabs at least every three months. If we diagnose pseudomonas colonization in this time period, we have the same chance of eradicating the infection, because of the switch that takes place six to 12 months after initial infection.”

Dr. Ratjen estimated that although a year of inhaled tobramycin without testing may be excessive, treatment should probably continue for at least six months.

—Mimi Zucker, PhD