摘要目的:探究高压氧(HBO)逆转肺炎克雷伯菌对三、四代头孢菌素的耐药性及其机制。方法:选取2017年1月至2017年12月济宁市第一人民医院呼吸与危重症医学科收集的肺炎克雷伯菌3株，均表现为AmpC(头孢菌素酶)和ESBLs(超广谱β-内酰胺酶)阳性，采用VITEK微生物分析系统对菌株进行鉴定。随后将3个菌株均分为对照组和HBO组，随后将其培养于不同浓度的三、四代头孢菌素中，采用琼脂二倍稀释法测定菌株对三、四代头孢菌素的最低抑制浓度(MIC)，平板计数法检测菌株活性。此外，提取菌株中的总蛋白，采用Western blotting检测缺氧诱导因子1α(HIF-1α)的表达水平；采用头孢他啶、头孢匹罗三维实验法和纸片确证扩散法分别对菌株中的AmpC和ESBLs进行检测。结果:与对照组相比，HBO处理后，3个菌株对三、四代头孢菌素的MIC值降低，活性降低，HIF-1α的表达降低( P<0.05)；此外，HBO处理明显降低了AmpC和ESBLs的检出率。 结论:HBO处理能够明显逆转肺炎克雷伯菌对三、四代头孢菌素的耐药性，其机制可能与HIF-1α通路被抑制及AmpC、ESBLs检出率的降低有关。

abstractsObjective:To study the effect of hyperbaric oxygen (HBO) treatment on reversing the drug resistance of Klebsiella pneumoniae against the third and the fourth generation of cephalosporins and its mechanism.Methods:Three strains of Klebsiella pneumoniae, collected in the Department of Respiratory and Critical Care Medicine of Jining No.1 People′s Hospital from the January of 2017 to the December of 2017, were used in this study, which all showed positive with cephalosporinase (AmpC) and extreme spectrum β -lactamase (ESBLs). The 3 bacterial strains were identified by VITEK microbial identification system, divided equally into control group and HBO group, and incubated with the third and the fourth generation of cephalosporins in different concentrations. The minimum inhibitory concentration (MIC) was determined by the two-fold agar dilution method, and the strains activity was determined by the plate counting method. In addition, the total protein in the strains was extracted, and the expression of HIF-1α was detected by using Western blotting method. The three-dimensional test of ceftazidime and cefpirome and the disc diffusion confirmatory method were used to detect AmpC and ESBLs in the strains, respectively.Results:Compared with the control group, the MIC values of the third and the fourth generation of cephalosporins, stain activity, and the expression of HIF-1 were all reduced in the HBO group( P<0.05). In addition, the HBO treatment significantly reduced the detection rates of AmpC and ESBLs. Conclusion:HBO treatment can significantly reverse the drug resistance of Klebsiella pneumoniae to the third and the fourth generation of cephalosporins, which may be related to the inhibition of the HIF-1 pathway and the reduction of AmpC and ESBLs.