Impact of Pseudomonas and Staphylococcus Infection on Inflammation and Clinical Status in Young Children with Cystic Fibrosis

Abstract

Objectives To assess the effects of Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF). Study design We studied 111 children < 6 years of age who had two Pa positive oropharyngeal cultures within 12 months. We examined bronchoalveolar lavage fluid (BALF) inflammatory markers (cell count, differential, IL-8, IL-6, neutrophil elastase), CF-related bacterial pathogens, exotoxin A serology, and clinical indicators of disease severity. Results Young children with CF with both upper and lower airway Pa infection had higher neutrophil counts, IL-8 and free neutrophil elastase levels, increased likelihood of positive exotoxin A titers, and lower Shwachman scores compared with those with positive upper airway cultures only. Sa was associated with increased lower airway inflammation and the presence of both Pa and Sa had an additive effect on concentrations of lower airway inflammatory markers. BALF markers of inflammation increased with numbers of different bacterial pathogens detected. Conclusions Young children with CF with upper and lower airway Pa infection have heightened endobronchial inflammation and poorer clinical status compared with children with only upper airway Pa infection. The independent and additive effects of Sa on inflammation support the importance of polymicrobial infection in early CF lung disease.

Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

“…Recently, there has been a growing appreciation for the significance of polymicrobial infections as well as the importance of a healthy flora for resistance to infection. Synergistic polymicrobial behavior has been implicated in a variety of disease states, including sepsis (46), cystic fibrosis lung infection (20,51,57,58), community-acquired respiratory infections (36,37,41), periodontal disease and other oral pathogen infection models (44,48), and UTI (7,63). Our increasing understanding of the complexity of infectious disease states and the contribution of multiple etiologic agents underscores the need for modern genetic and molecular diagnostics along with treatment tailored accordingly, a need especially important for chronic and recurrent diseases, such as UTI, that are increasingly recalcitrant to treatment.…”

Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

“…Some of the most common isolates from human bronchiolar lavage samples of CF patients are Pseudomonas aeruginosa, S. aureus, Streptococcus milleri group (SMG) pathogens, Burkholderia cepacia, Stenotrophomonas maltophilia, H. influenzae, and C. albicans. However, this list ignores members of the normal flora that are not regularly screened in the clinical laboratory (143,179,182,194). Several interesting findings and trends from coinfections with several of these pathogens will be discussed.…”

Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

“…Others subsequently confirmed the association between P. aeruginosa infection and mortality (114,138,277,425). In addition to decreased survival, P. aeruginosa infection is associated with poorer lung function (277,311,325,326,445,655), worse chest radiologic imaging scores (4,277,326,493,511), slower growth of the patient (445,511), and increased frequency of daily cough (4). For example, Schaedel and colleagues examined factors influencing pulmonary function in the entire CF population of Sweden over the age of 7 years.…”

“…As a result, rather than being eradicated, P. aeruginosa bacteria actually increase in number over time (506) and may reach densities as high as 10 10 to 10 11 CFU/ml of sputum (2,213). The ineffectiveness of the immune response allows the establishment of a relentless cycle whereby persistent bacteria cause increased inflammation that itself leads to increased bacterial densities and in turn more inflammation (511) (Fig. 2).…”