Novel Therapy Bypasses Antibiotic Resistance in Cystic Fibrosis Patients

Researchers have developed a promising new approach for treating the chronic bacterial infection found in the lungs of most cystic fibrosis (CF) sufferers.

The lungs are the site of the most life-threatening effects of CF. The production of a thick, sticky mucus increases the likelihood of infection, decreases the ability to protect against infection, causes inflammation and swelling, decreases the functional capacity of the lungs, and may lead to emphysema. People with CF live with chronic populations of bacteria in their lungs, and lung infection is the major cause of death for those with CF.

Initially, common bacteria such as Staphylococcus aureus and Hemophilus influenzae colonize and infect the lungs. Eventually, however, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics.

Many bacteria common in cystic fibrosis are resistant to multiple antibiotics and require weeks of treatment with intravenous antibiotics such as vancomycin, tobramycin, meropenem, ciprofloxacin, and piperacillin. Inhaled therapy with antibiotics such as tobramycin and colistin is often given for months at a time in order to improve lung function by impeding the growth of colonized bacteria. Oral antibiotics such as ciprofloxacin or azithromycin are sometimes given to help prevent infection or to control ongoing infection.

Investigators at the University of Calgary (Alberta, Canada) used advanced culture-independent and microbiological approaches to demonstrate that within the complex and dynamic bacterial communities in the lungs of CF patients, the Streptococcus milleri group (SMG) established chronic pulmonary infections. At the onset of 39% of acute pulmonary infections, SMG was the numerically dominant pathogen. Later on more pathogenic organisms such as P. aeruginosa rise to the forefront of the infection.

In their paper published in the September 23, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) the investigators reported that treatment of the SMG infection could modify the chronic bacterial population of the CF lung to such an extent that it prevented the establishment of P. aeruginosa infection.

Clinical studies have already indicated the efficacy of treating SMG in CF patients with serious lung infections. "This is important new information,” said senior author Dr. Michael Surette, professor of medicine at the University of Calgary. "In our small patient group, the laboratory findings have been used to guide treatment, with positive results.”

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