目的观察青蒿琥酯联用头孢曲松钠对铜绿假单胞菌的抗菌效果。方法分别采用纸片法和液体稀释法检测单独应用青蒿琥酯及与头孢曲松钠联用对铜绿假单胞菌标准株和临床分离株的抑菌活性,测定最低抑菌浓度(MIC)和最低杀菌浓度(MBC);以铜绿假单胞菌标准株最小致死量(MLD)建立小鼠感染模型,分为对照组(0.9%NaCl溶液),菌液组,青蒿琥酯组,头孢曲松钠组,联合应用组一[菌液+15mg/(kg·d)+200mg/(kg·d)]及联合应用组二[菌液+30mg/(kg·d)+200mg/(kg·d)],分别给予相应药物治疗,检测受试小鼠的血液细菌清除情况及小鼠血清内毒素(LPS)和白细胞介素(IL)-17水平。结果体外实验结果显示单独应用青蒿琥酯对铜绿假单胞菌标准株及临床分离株均无抑杀作用,单独应用头孢曲松钠对铜绿假单胞菌标准株和分离株的MIC值分为156.25和312.5μg/ml,MBC值分别为312.5和625μg/ml;其中以3mg/ml青蒿琥酯联用1/8 MIC头孢曲松钠对临床分离株的协同作用最强,FIC指数达到0.125,以23.44μg/ml青蒿琥酯联用1/4MIC头孢曲松钠对铜绿假单胞菌标准株的FIC指数达到0.25;动物实验结果显示青蒿琥酯和头孢曲松钠联用组血液细菌数量分别为(180±20)CFU/ml和(163±25)CFU/ml,明显低于菌液组(960±53)CFU/ml(F=486.53,P<0.01)和头孢组(300±20)CFU/ml(F=34.907,P<0.01)。在观察期内,青蒿琥酯联合头孢曲松钠组小鼠血清IL-17含量24h时[(151.5±20.3)pg/ml,(197.8±12.8)pg/ml]达到最高峰,与菌液组(87.5±5.2)pg/ml和头孢治疗组(120.1±20.2)pg/ml比较差异均有统计学意义(F24h=45.831,P<0.01,F48h=12.183,P<0.01,F24h=14.003,P<0.01,F48h=8.378,P<0.05)。观察后期48h联合用药组小鼠血清LPS水平[(46.9±5.0)EU/L,(15.4±1.6)EU/L]与菌液组(57.2±3.4)EU/L比较差异有统计学意义(F=173.073,P<0.01),与头孢治疗组(37.4±14.3)EU/L比较差异有统计学意义(F=10.143,P<0.05)。各组LPS水平,IL-17水平,菌量水平基本一致。结论体内和体外联合应用青蒿琥酯和头孢曲松钠均可对铜绿假单胞菌产生协同抗菌效应。 Objective To observe the antibacterial effect of artesunate combined with ceftriaxone on Pseudomonas aeruginosa. Methods The antibacterial activities of artesunate alone and in combination with ceftriaxone sodium on standard strains and clinical isolates of Pseudomonas aeruginosa were detected by disk and liquid dilution methods, respectively. The minimum inhibitory concentration (MIC) And the lowest bactericidal concentration (MBC). The mouse model of infection was established with the minimum lethal dose (MLD) of Pseudomonas aeruginosa standard strain and divided into control group (0.9% NaCl solution), bacterial liquid group, artesunate group, (Control group), the control group (control group), the control group (control group) · D)], were given the appropriate drug treatment, test the blood of mice were tested for bacterial clearance and serum endotoxin (LPS) and interleukin (IL) -17 levels. Results The results of in vitro experiments showed that artesunate alone had no inhibitory effect on standard strains and clinical isolates of Pseudomonas aeruginosa. MIC value of ceftriaxone sodium alone against standard strains and isolates of Pseudomonas aeruginosa MBC value of 312.5 and 625μg / ml respectively; the synergistic effect of 3mg / ml artesunate with 1/8 MIC ceftriaxone sodium on clinical isolates was the strongest, FIC index reached 0.125, the FIC index of Pseudomonas aeruginosa standard strain with 0.254μg / ml artesunate combined with 1/4 MIC ceftriaxone standard reached 0.25; the animal experiments showed that artesunate combined with ceftriaxone sodium The number of blood bacteria were (180 ± 20) CFU / ml and (163 ± 25) CFU / ml respectively, which was significantly lower than that of the bacterial solution group (960 ± 53 CFU / ml, F = 486.53, 300 ± 20) CFU / ml (F = 34.907, P <0.01). During the observation period, the serum IL-17 level of artesunate combined with ceftriaxone sodium group reached the peak at the time of 24h [(151.5 ± 20.3) pg / ml, (197.8 ± 12.8) pg / ml] (87.5 ± 5.2) pg / ml and cefazolin treatment group (120.1 ± 20.2) pg / ml, the difference was statistically significant (F24h = 45.831, P <0.01, F48h = 12.183, P <0.01, F24h = 14.003, P <0.01, F48h = 8.378, P <0.05). The level of serum LPS (48.9 ± 5.0) EU / L and (15.4 ± 1.6) EU / L in the combination group at 48 h after the last observation were significantly different from that of the bacterial culture group (57.2 ± 3.4) EU / L = 173.073, P <0.01). The difference was statistically significant (F = 10.143, P <0.05) compared with EU / L of 37.4 ± 14.3 in cefotaxime treatment group. The levels of LPS, IL-17 and the amount of bacteria in each group were basically the same. Conclusion Combination of artesunate and ceftriaxone in vivo and in vitro can produce synergistic antibacterial effect on Pseudomonas aeruginosa.