Staphylococcus Aureus in CF Airways Change With Age, Antibiotic Use, Study Says

Different types of Staphylococcus aureus can be found persistently in the airways of cystic fibrosis (CF) patients, but this bacteria population is influenced by age and prior antibiotic treatment, a new study says.

The study, “Antibiotic Treatment and Age Are Associated With Staphylococcus aureus Carriage Profiles During Persistence in the Airways of Cystic Fibrosis Patients,” was published in the journal Frontiers in Microbiology.

People with CF often experience chronic bacterial infections of the airways, which can lead to decreased lung function. S. aureus is one of the earliest bacteria present in the airways of people with CF, as early as infancy.

S. aureus is known to persist in the airways of CF patients for extended periods, and to proliferate by creating clones of itself. Over time, these clones accumulate slight genetic variations and originate different S. aureus types.

However, there is a lack of knowledge about the different S. aureus types present in the airways of CF patients, and the dynamics of their long-term presence in the airways.

In the study, scientists at the University Hospital Münster in Germany investigated the S. aureus types present in the airways of people with CF over a 21 month-period, and their association with the patients’ lung disease, age, and history of antibiotic treatment.

“We hypothesized that patients would differ in their clinical status depending on S. aureus clonal carriage profiles during persistence,” the researchers wrote.

The study enrolled 195 CF patients attending CF centers in Germany and Austria. S. aureus was isolated from samples collected from the nose, throat, and sputum of patients over a total of 1,120 visits to CF centers.

Identification of different S. aureus types was done by analyzing the bacterial DNA at the SpA gene. This gene encodes protein A, a protein present at the surface of S. aureus bacteria. The method used to study the bacterial DNA at the SpA region is called spa-sequence typing.

Of the 195 who participated in the study, 183 remained S. aureus-positive throughout the study, indicating persistent infection.

Researchers identified 265 different types of S. aureus from 1,929 patient samples where the bacteria was present. CF patients carried on average 3.21 S. aureus types in their airways.

Eight types of S. aureus were found in more than 10 people — t084, t091, t008, t015, t002, t012, t364, and t056 — making them the most common, or prevalent, types among CF patients in the study.

Depending on the types of S. aureus found in their samples, patients were divided into four groups with some patients matching the criteria for more than one group.

The first group included 68 patients in whom a prevalent type of S. aureus was identified in samples from at least half of their visits. In the second group, 64 patients in whom only one type of S. aureus was identified during the entire study were included.

Patients in the third group (65) had a dominant type of S. aureus which was present in samples from all visits, while other types of S. aureus were only present in samples from some visits.

Finally, the fourth group included 33 patients who had a mix of genetically-related S. aureus types in more than half of their visits.

Interestingly, none of the different groups had a higher risk of pulmonary exacerbations or worse lung function.

“There was not a special S. aureus … type, which we identified to be associated with a more severe lung disease during our study,” the researchers wrote. The team suggested that all the S. aureus types “are able to cause lung disease, and a more severe course of the CF disease may [be] dependent on other most likely host related factors.”

Transmission of different S. aureus types within centers was found to be low, and any possible S. aureus types transmitted between patients did not persist for long.

Data also showed that antibiotic resistance was generally low in the S. aureus types isolated from patient samples. About 2% of S. aureus were resistant to oxacillin, an antibiotic similar to methicillin, which indicates a low proportion of methicillin-resistant S. aureus (MRSA) in samples from these patients.

A higher number of past antibiotic treatment cycles was seen to be associated with a higher chance of carrying only one type of S. aureus. According to the researchers “[T]he fact that antibiotic treatment affected the number of different clones [S. aureus types], indicates that CF patients are highly susceptible for the acquisition of new S. aureus strains, if not treated with antibiotics.”

Another finding of the study was that older CF patients were more likely to either have a mix of genetically-related S. aureus types, or a dominant type of S. aureus.

According to the team, this indicates that slight genetic alterations that “cause a less pro-inflammatory response by protein A” are present in S. aureus types “which are optimized for persistence in the airways.” Presumably, by avoiding triggering an inflammatory response in the host, these S. aureus types are able to remain present in the airways for longer.

Overall, “there was a significant association of antibiotic therapy and age on S. aureus … profiles in CF patients indicating that antibiotic therapy prevents acquisition of new clones, while during aging of patients with persisting S. aureus, dominant clones were selected and mutations in the spa … region accumulated,” the team wrote.