Introduction Nosocomial pneumonia is a significant cause of inhospital morbidity and mortality. Oral care interventions have great potential to reduce the occurrence of nosocomial pneumonia. Studies using topical antiseptic agents yielded mixed results. We hypothesized that the use of chlorhexidine for oral decontamination would reduce the incidence of nosocomial pneumonia in patients requiring mechanical ventilation.
The purpose of this study is to examine the in vitro modulatory effect of tigecycline on staphylococcal superantigen-induced T-cell activation and cytokines and chemokines production by human peripheral blood mononuclear cells (PBMC). Isolated human PBMC from ten healthy volunteers were stimulated by staphylococcal enterotoxin B (SEB) and Staphylococcal toxic shock syndrome toxin-1 (TSST-1) superantigens with varying concentrations of tigecycline. Cytokines IL-1 beta, IL-6, TNF-alpha, and chemokines MIP-1 alpha and MIP-1 beta concentrations were measured along with T cell proliferation. Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.
SUMMARY
Objectives
In patients with ventilator associated pneumonia (VAP), Pseudomonas aeruginosa type III (TTSS) secreting isolates have been li nked to poor clinical outcomes. Differential expression of matrix metalloproteinases (MMPs) induced by type III effector proteins may herald an irreversible lung injury.
Methods
Serial bronchoalveolar lavage fluids collected from 41 patients with P. aeruginosa at onset of VAP, day 4, and day 8 after antibiotic therapy were assayed for MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-2 macroglobulin levels.
Results
At the onset of VAP, isolates secreting ExoU had the highest MMP-9 levels. The response to antimicrobial therapy showed a differential drop in MMPs with significant decrease in MMP-8 and MMP-9 levels on days 4 and 8 in patients with TTSS− compared to TTSS+ phenotype. The ratio of MMP-9/TIMP-1 was significantly associated with α-2 macroglobulin at end of therapy (r=0.4, p=0.02). Patients who survived had a lower MMP-9/TIMP-1ratio than those who died (p=0.003).
Conclusions
VAP linked to P. aeruginosa Type III phenotype portrays a divergent antibiotic treatment response in regards to the concentrations of metalloproteinases in the alveolar space. The imbalance between MMP-9 and TIMP-1 may determine the intensity of alveolocapillary damage and ultimate outcome of Pseudomonas aeruginosa VAP.
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