Reduction in Pseudomonas aeruginosa sputum density during a cystic fibrosis pulmonary exacerbation does not predict clinical response

Abstract

Background: Pulmonary exacerbations (PEx) are critical events in cystic fibrosis (CF), responsible for reduced quality of life and permanent loss of lung function. Approximately 1/4 of PEx are associated with failure to recover lung function and/or resolve symptoms. Developing tools to optimize PEx treatment is of paramount importance. Methods: We retrospectively audited all adults infected with Pseudomonas aeruginosa, experiencing PEx necessitating parenteral antibiotic therapy from 2006-2012 from our center. Quantitative analysis of sputum at admission, twice-weekly during hospitalization, and end of therapy were compared to baseline (most recent healthy) and follow-up (after PEx) samples. Change in P. aeruginosa burden from baseline was assessed for any and all morphotypes (ALL), as well as mucoid (MUC) and non-mucoid (NON) isolates specifically. PEx were identified as failures if >90% of baseline pulmonary function was not recovered. Results: Forty-six patients meeting the above inclusion and exclusion criteria experienced 144 PEx during this time (median 3, IQR 2-6). Patients were treated for a median 14 days (IQR 13-16). No increase in ALL, MUC or NON were detected at PEx, nor was there an association between change in sputum density and magnitude of lung function decline. PEx failures were observed in 30% of events. Reductions of at least 1-log and 2 log P. aeruginosa sputum density was observed in 57% and 46% (ALL), 73% and 55% (MUC) and 58% and 46% (NON) of PEx, respectively. Factors associated with greater reduction of P. aeruginosa sputum density included choice of β-lactam antibiotic, antibiotics with in vitro predicted activity and treatment duration. PEx associated with reductions in P. aeruginosa sputum density were not associated with a reduced risk of PEx failure. Conclusions: Enhanced killing of P. aeruginosa during PEx does not predict improved clinical outcomes. Studies accounting for the polymicrobial nature of CF respiratory disease and the heterogeneity of P. aeruginosa causing chronic infection may enable the identification of a more appropriate pathogen(s) based biomarker of PEx outcomes.