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Summary: To study the resistant mechanism and clinical significance of pseudomonas aeruginosato β-lactam antibiotics, the outer membrane permeability rate of 30 P. aeruginosa strains to 5 β-lactam antibiotics was measured and their production of β-lactamase and the β-lactamase genes theycarried detected. Furthermore, the relationship between the permeability, β-lactamase and theclinical effects of β-lactam antibiotics was observed. By using 14C-penicillin and liquid-scintillantisotope assay, the affinity of penicillin binding proteins (PBPs) was measured and their roles inthe resistant mechanism studied. It was revealed that the permeability rate was higher in sensitivestrains than in resistant ones (P＜0. 05). All strains harbored 1-4 β-lactamase genes and producedβ-lactamase. Higher permeability rate and higher degree of stability to β-lactamase indicated betterclinical therapeutic effects. The affinity of PBPs changed little without regard to the permeabilityand β-lactamase. These results suggested that the permeability of outer membrane and β-lacta-mase, but not PBPs, played important roles in the resistant mechanism of P. aeruginosa to β-lac-tam antibiotics and affected the clinical therapeutic effectiveness of some patients.