Antibiotic Treatment and Age Are Associated With Staphylococcus aureus Carriage Profiles During Persistence in the Airways of Cystic Fibrosis Patients

Abstract

Background: Staphylococcus aureus is one of the most isolated pathogens from the airways of cystic fibrosis (CF) patients. There is a lack of information about the clonal nature of S. aureus cultured from CF patients and their impact on disease. We hypothesized that patients would differ in their clinical status depending on S. aureus clonal carriage profiles during persistence. Methods: During a 21-months prospective observational multicenter study (Junge et al., 2016), 3893 S. aureus isolates (nose, oropharynx, and sputa) were cultured from 183 CF patients (16 German centers, 1 Austrian center) and subjected to spa-sequence typing to assess clonality. Data were associated to lung function, age, gender, and antibiotic treatment by multivariate regression analysis. Results: Two hundred and sixty-five different spa-types were determined with eight prevalent spa-types (isolated from more than 10 patients): t084, t091, t008, t015, t002 t012, t364, and t056. We observed different carriage profiles of spa-types during the study period: patients being positive with a prevalent spa-type, only one, a dominant or related spa-type/s. Patients with more antibiotic cycles were more likely to be positive for only one spa-type (p = 0.005), while older patients were more likely to have related (p = 0.006), or dominant spa-types (p = 0.026). Two percent of isolates were identified as methicillin-resistant S. aureus (MRSA) and evidence of transmission of clones within centers was low. Conclusion: There was a significant association of antibiotic therapy and age on S. aureus carriage 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-repeat region accumulated.

How Bacterial Adaptation to Cystic Fibrosis Environment Shapes Interactions Between Pseudomonas aeruginosa and Staphylococcus aureus

“…A 21-month longitudinal study performed on 183 CF patients depicted that the clonal diversity of S. aureus strains decreased as patient aged, pointing out that some isolates tended to adapt more efficiently and dominate the airway sphere during infection history ( Westphal et al, 2020 ). Several studies indeed highlighted that S. aureus isolates evolve in the CF lung environment and acquire features leading to better-fitted isolates ( Figure 2 ; Chatterjee et al, 2008 ; Treffon et al, 2018 , 2020 ; Herzog et al, 2019 ; Lennartz et al, 2019 ; Tan et al, 2019 ; Westphal et al, 2020 ).…”

Staphylococcus aureus Pathogenicity in Cystic Fibrosis Patients—Results from an Observational Prospective Multicenter Study Concerning Virulence Genes, Phylogeny, and Gene Plasticity

“…The obtained S. aureus isolates (n = 3893) were distinguished deploying the spa-typing method [58]. The "Based upon repeat pattern" method (BURP, Ridom StaphType software) was used to analyze the clonal relatedness of different spa-types differentiating 266 spa types (Supplementary Materials Tables S1 and S2) [29,59]. In this analysis, every isolate was scanned for the presence of 25 virulence genes and the 4 agr-specificity groups, using single and multiplex PCR.…”

“…In most cases, a long-term colonization with individual S. aureus clones is observed [4]. Persistent S. aureus clones tend to form a genetically and particularly phenotypically heterogeneous population with S. aureus acquisition most likely outside the hospital with only minor transmission events [6][7][8]. The genetical diversity is fostered by mutations and horizontal gene transfer with persistence of dominant lineages and a continuous process of intra-host adaptation [6,9].…”

“…Further analyses revealed associations between antibiotic treatment, age, and S. aureus clonal carriage profiles during persistence assessed by spa-sequence typing of almost 4000 S. aureus isolates from 183 CF patients during a 21-month prospective study [29]. Patients receiving intensive antibiotic therapy regimens more likely carried S. aureus isolates during persistence, which belonged to only one spa-type [7], while older patients carried isolates with related spa-types with mutations of the repeat region including deletions, duplications of repeats or point mutations within repeats, or dominant spa-types cultured [7].…”

Staphylococcus aureus and Cystic Fibrosis—A Close Relationship. What Can We Learn from Sequencing Studies?

“…Only few strains were occasionally shared between individuals belonging to the same household or due to clinical exposure. Some MLST-types were distributed throughout all centres and included MRSA as well as MSSA, which resembles the S. aureus carriage profile in the study of Westphal et al described as "prevalent" [94]. In addition to the conserved core genes, the authors analysed the variable accessory gene content.…”