Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease

Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks. Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients (N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication (P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUC(ROC) = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance (P = 0.0001), systemic steroid use (P = 0.0024) and presence of P. aeruginosa (P = 0.0282). Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria.