Among Gram-positive pathogens, Staphylococcus aureus is the leading cause of death from nosocomial pneumonia. The bacterium developed progressive resistance to beta-lactams, and methicillin-resistant strains emerged in the 1980s. In consequence, vancomycin has become the drug of choice for treatment of this infection over the last decade, based on susceptibility tests and the serum antimicrobial levels recorded. However, half of the patients treated with vancomycin have died. In contrast, in patients receiving beta-lactams for pneumonia caused by methicillin-sensitive S. aureus, survival is the rule. These observations, together with the emergence of isolates with reduced susceptibility to glycopeptides, raised concern about the use of vancomycin as standard therapy for pneumonia caused by Gram-positive cocci. Maintaining tissue levels above minimal inhibitory concentration is vital to successful clinical outcome. Optimizing treatment focusing on this goal and new antimicrobials provide new opportunities to improve survival. (Crit Care Med 2001; 29[Suppl.]:N82-N86)

BackgroundThe bronchial mucosa is protected by a specialized immune system focused on the prevention of colonization and infection by potentially pathogenic microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved in this mechanism. A defective immune barrier may facilitate the recurrent presence of PPMs in COPD.PurposeThe aim of this study was to determine IgA-mediated bronchial specific immune responses against Pseudomonas aeruginosa in stable patients with severe disease.MethodsCOPD patients with good-quality sputum samples obtained during stability were included and classified according to the presence or absence of chronic bronchial colonization by P. aeruginosa. Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and expressed as ratios, using the pooled level of 10 healthy subjects as reference (optical density450 patient/control).ResultsThirty-six stable COPD patients were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of specific IgA against P. aeruginosa in stable non-colonized patients were lower than those in healthy subjects (IgA ratio: median =0.15 [interquartile range {IQR} 0.05–0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59–2.79]) (p<0.001, Mann–Whitney U test), with figures equivalent but not exceeding the reference value.ConclusionIgA-based immune response against P. aeruginosa was low in severe COPD patients. Levels of specific IgA against this microorganism were higher in colonized patients, but did not attain clear-cut levels above the reference. An impaired local response against P. aeruginosa may favor chronic colonization and recurrent infections in severe COPD.