Investigation Of Extracorporeal Bactericidal Activity Of Amikacin To ESBLs-producing E.coli Infections

The E. coli producing ESBLs is one of the most important pathogens of nosocomial infection. Carbopenems antibiotics are the first choice of therapy, but the selective pressure is high, and easy to induce secondary infection of fungi and so on. Of many drug sensitivity surveillance, the sensitivity of ESBLs - producing E. coli to Amikacin is rather high besides Imipenem, eg. In our hospital, 58 strains are sensitive to Amikacin among 94 ESBLs - producing E. coli isolated from January 2001 to January 2003. The present study is to investigate the bactericidal activity of Amikacin of 20 ESBLs - producing E. coli strains to explore the possible role of amikacin in the management of ESBLs - producing E. coli infections.Materials1. Isolates selected for experiment ; 20 ESBLs - producing E. coli strains sensitive to Amikacin are isolated in our hospital from January 2001 to January 2003. Reference strain; E. coli ATCC25922.2. Reagent: Amikacin3. Equipment; M -H broth; Columbia base agar, et al.Methodology1. Blood - drug - concentration - time curve and the average Blood - drug - concentration of 2,4,6,8,12h of Amikacin in vivo based on the data of Zhangyi et al. in Clinical Pharmacokinetics And PAE In Vivo of AMK.2. Assay the MIC and MBC of strains selected; Reference strain :E. coli ATCC259223. Time - killing curve; the concentration of AMK are32,22,19, 16,10,2mg/l,the correspondence time of observation are 2,4,6,8, 12,12h. The inoculum are 106CFU/ml in every tube, incubate under 35 ℃ overnight.Results1. MIC of reference strain-. MIC of E. coli ATCC25922 is in 0.5 ~4mg/l.2. The average MIC of testing strains is 2. 14mg/l, and average MBC 17.75mg/l.3. The time - killing curve of all the strains demonstrates that in a concentration of 22 mg /I AMK, the amount of bacteria in the tube have decreased lower than 0. 1% of the initial inoculum after 4 hours, with a log10CFU <3( p <0.05). However, the amount of bacteria in the tube is more than 0.1% of the initial inoculum with a log,0CFU > 3 (p <0.05) after 12 hours in a concentration of 10mg/l;the same is true of 16mg/l after 8h. while in a concentration of 19mg/l, the a-mount of bacteria is close to 0.1% of the initial inoculum with a log10 CFU=3( p>0.05) after 6 hours.DiscussionThe antibacterial activity can be judged by the value of MIC. It is recognized that a C^/MIC of 4 - 8 be good enough for mild to moderate infection, and 8 will be better for serious one. In this study, the Cmax/MIC is 17.76 approximately, and therefore AMK should be effective when treating the infection caused by ESBLs -producing E. cob'.Another factor in evaluating antibacterial activity we use is II(72) , which should be 100 -300 or >300 for the mild to moderateinfection or severe infection respectively. In this study, 11(72) is 252~ 276, AMK should be effective to the mild to moderate infectioncaused by ESBLs - producing E. cob*.As it has been shown before, the bactericidal action of AMK is within 4 hours after IV administration, accumulative PAEof 24h of the aminoglycosides to gram - negative bacillus can last more than 30 hours, which will restrain the growth of bacteria even when the concentration is far lower than MIC.ConclusionThe clinical routine dosage of AMK has shown a satisfied bactericidal action on the ESBLs - producing E coli, especially, within 4 hours after the administration, which might be a positive evidence supporting the initiation of AMK when managing a infection by ESBLs -producing E coli.