Pseudomonas aeruginosa serology and risk for re-isolation in the EPIC trial

Abstract

Background: The prognostic value of Pseudomonas aeruginosa serology for antibiotic therapy in cystic fibrosis patients is not well understood.

Methods: Using five antigens from two ELISAs, we assessed whether positive serology in CF patients participating in the multi-center Early Pseudomonas Infection in Children (EPIC) trial would predict treatment failure, time to pulmonary exacerbation and risk for recurrent P. aeruginosa isolation post eradication.

Results: Baseline positive P. aeruginosa serology was not significantly associated with failure of initial P. aeruginosa eradication measured at week 10 (adjusted for baseline culture) but seropositivity to the antigens alkaline protease and exotoxin A was significantly associated with increased risk for recurrent P. aeruginosa isolation during the 60 week post eradication follow-up period (p=0.003 and p=0.001 respectively). There was no association between baseline seropositivity and time to pulmonary exacerbation.

Conclusion: P. aeruginosa serology may complement culture results in clinicians' efforts to successfully monitor recurrence of early P. aeruginosa in CF patients.

Fig. 1

Distribution of individual antigen titers by concurrent culture status for all 975 serum samples. Pa+ indicates P. aeruginosa positive, Pa− indicates P. aeruginosa negative. Hash lines are the median values, boxes represent the 25th and 75th percentiles (inter-quartile range), whiskers extend to minimum and maximum or 1.5× the inter-quartile range (whichever is smaller), outliers are marked as circles.

Fig. 2

Culture positivity and seropositivity over time. The solid black line shows the proportion culture positive for P. aeruginosa across each visit among the 303 subjects with available serology. The dashed lines show the proportion of samples seropositive at each visit for each combined ELISA. A combined ELISA is defined as seropositive if any one of the three antigens in an ELISA has titer at least 100.

Fig. 3

Baseline serology titers by respiratory culture status using modified Leeds criteria. Subjects were classified as ‘Pa free’ if they were clear of P. aeruginosa from baseline through end of study, ‘Intermittent’ if they had less than half of all available cultures testing positive for P. aeruginosa, and ‘Chronic’ if they had half or more of all available cultures testing positive for P. aeruginosa. Hash lines are the median values, boxes represent the 25th and 75th percentiles (inter-quartile range), whiskers extend to minimum and maximum or 1.5× the inter-quartile range (whichever is smaller), outliers are marked as circles.