Shuanghuanglian Qingkailing Esbls-producing Escherichia Coli Antimicrobial Effect

Objective Observing the antibacterial activity of Chinese medicine Shuanghuanglian and Qingkailing towards ESBL-producing escherichia coli, synergistic effect of antibacterial of combined application of Chinese medicine and Cefoperazone-sulbactam, proportion and time table of combined application of Chinese medicine and Western Medicine through bacteriostasis experiment in vitro and in vivo to investigate the effect mechanism of drug resistance elimination of ESBL-producing escherichia coli by Chinese medicine.Methods (1)Applying ESBL-producing escherichia coli strain that obtained from clinical to build drug-resistant bacteria model after selection and confirmation of ESBLs. Determination MIC of drugs by double dilution method.Making up liquid medicine of Shuanghuanglian, Qingkailing and Cefoperazone-sulbactam. Adding relevant liquid medicine according to groups of experiment to do the double dilution. There were 12 groups:negative control group, SHL group, QKL group, CPZ/SBT group, SHL+CPS gr Chinese medicine and Western Medicine combination groups respectively 4h,6h,8h's later.Observeng with an unaided eye the MIC after cultured in 35℃for 24h. (2) 60 rat models were divided into 6 groups at random.There were 6 rats in each group. They were model group, CPS group, SHL+CPS/H group, QKL+CPS/H group, SHL+CPS/L group and QKL+CPS/L group. Bulding rat septicemia model through tail vein injection of multiple drug-resistant escherichia coli(germ-containing quantity was 2.5×108/ml). If hemoculture result was positive afer injection of bacteria suspension for 1h, and the rats appeared symptom of septic shock even death, it was regarded as successful model. Then began to give the remedy. The model group was injected 0.9%Sodium Chloride Injection in peritoneal. CPS group was injected CPS, 350mg/kg, in two divided doses daily. SHL+CPS/H group was injected Shuanghuanglian, 140mg/kg, qd, and injected CPS,350mg/kg, in two divided doses daily within 6h. QKL+ CPS/H group was injected Qingkailing 2.3ml/kg, qd, and injected CPS,350mg/kg, oup, QKL+CPS group, SHL+CPS 4h group, SHL+CPS 6h group, SHL+CPS 8h group, QKL+CPS 4h group, QKL+CPS 6h group and QKL+CPS 8h group.Adding bacteria suspension to the tubes of each group, the final inoculation quantity was 5×105CFU/ml. Adding 0.5ml broth and 0.5ml Cefoperazone-sulbactam toin two divided doses daily within 6h.SHL+CPS/L group was injected Shuanghuanglian 140mg/kg, qd, and injected CPS,230mg/kg, in two divided doses daily within 6h. QKL+CPS/L group was injected Qingkailing2.3ml/kg, qd, and injected CPS,230mg/kg, in two divided doses daily within 6h. Consecutive administration for 5 days. Observing and noting the death rate, weight, temperature and general condition. Drawed blood before administration and after 5 days to do the blood culture and leucocyte count. Did the histopathology of lung, thymus gland, spleen and liver after the experiment.Results (1) The MIC of Shuanghuanglian, Qingkailing and Cefoperazone-sulbactam towards ESBL-producing escherichia coli was 23.04 g/L,62.50 mL/L,39.06 mg/L respectively. The best effect group was SHL+CPS 6h group, MIC of Shuanghuanglian was 98% lower(1.44 g/L), MIC of Cefoperazone-sulbactam was 50% lower(19.53 mg/L). The best effect group was QKL+CPS 4h group, MIC of Qingkailing was 93.75% lower(3.91 mL/L), MIC of Cefoperazone-sulbactam was 75% lower(9.76 mg/L). (2) After therapy survival time of SHL+CPS/H group was significantly extended(P<0.05). Compared with model group and Western medicine group,the temperature of rats in groups, which administrated by combination of Chinese medicine and Western Medicine,declined obviously (P<0.05) and fast (P<0.01). The activity of these groups improved obviously after infected for 2～3d,and returned to normal basically (P<0.01/P<0.05), absolute value of leukocyte declined significantly (P<0.05), blood culture showed clearance rate of bacteria was higher. The pathological lesions of these groups alleviated obviously. The weight of rats of SHL+CPS/H group, SHL+CPS/L group and QKL+CPS/H group increased markedly (P <0.05).Conclusion Proved by bacteriostasis experiment in vitro and in vivo, Shuanghuanglian and Qingkailing had bacteriostatic action to ESBL-producing escherichia coli to some extent. Cefoperazone-sulbactam combined application with Shuanghuangian or Qingkailing had obvious synergistic effect of antibacterial activity in vitro. Shuanghuanglian and Qingkailing enhanced sensitivity of Cefoperazone-sulbactam towards ESBL-producing escherichia ESBL-producing escherichia. Drug-resistant bacteria were converted to sensitized bacteria, mechanism of which had a relationship to eliminate phasmid R. Chinese medicine combined with Western medicine enhanced effect of antibacterial activity,had better anti-inflammatory effect in vivo,protected infected rat models,lowerde the temperature, alleviate inflammatory response,controled infection symptom,modulated metabolism metabolism, protected vital organs, alleviated pathological lesions, improved curative effect, reduced dosage of Western medicine had the effect of strengthen body resistance and eliminating evil.