In Vivo And In Vitro Antibacterial Activities Of Mezlocillin/Sulbactam And Evaluation Of Its Clinical Efficacy Against Infectious Disease

OBJECTM To study the antibacterial activity of MZBT (mezlocillin/sulbactam forl:4) and other antibiotics in vitro and in vivo against clinical strans and to compare thesusceptibility of MZBT and MZL against Escherichia coli and Klebsiella pneumoniaeWhich produce ESBLs, and to evaluate the clinical efficacy and safety of MZBT andTimentin.METHODS 47 clinical isolates of Eshcherichia coli and 35 clicical isolates ofKiebsiella pneumoniae were collected from our hospital in 2000. 27 isolates ofEshcherichia coli and l5 isolatos of Klebsiella pneumoniae were identified as extended-spectrum β-lactamases(ESBLs) Producers by Nitrocephin-disk method, double-disksynergy test(DDST) and E-test. (l)The MICs of Mezlocillin/sulbactam (MZBT),tazoxin(TZXL), Mezlocillin (MZL) and timentin(TMT) against l79 clinical stheins weredetermined by agar dilution method.(2) A randomized selfcontrol clinical study wasperformed in l0 healthy male voluneers, Mezloc illin/Sulbactarn(MZBT) wasadministered in 3.75g, iv (includng 3.0g Mezlociline and 0.75g Sulbactarn), Mezlocilinewas administored 3.0g. To contrast the SBAs of the two drugs, the blood samples weretaken in 0.5h. 7h after adrninistraion.(3) The MBCs of MZBT and MZXT againstEscherichia coli and xiebsiella pneumoiae which produce β -lactanase or ESBLs weredetermined by micro-dilution method.(4)A randomized contrl led clinical trial methodwas performed to evaluate the clinical efficacy and safety of MZBT and TMTRESULTS (l) The antibacterial activity in vitro of MZBT against clhacal isolates waslto 2 times higher than that of MZL. In vitro, MZBT has higher susceptibility than MZLagainst bacteria that have higher rate of producing β -lacthease,such as Escherichia coli6Eniffebacter species,Acilldebacter sPecies,et al.(P<0.0l), and much more suscePiblethan TMT against Entefobacter and Other G- bacilli (P<0.0l). MZBT and TZXL havesimilar antibacterial spectrUIn and suscePtibility rate. MIC. of TZXL was lto 2 timeslower than that of the MZBT,but there was no significan difference.(2) The peakSBAs of MZBT against StaPhylococcus aureus' StaPhylococcus ePidermidis'Enterobacter cloacae. Escherichia coli Which produce 0 -lactamase were higher thanMezlociline, Mezlociline and SulbaCtaIn showed good synersism. The antibacterialactivities of MZBT against K.pneuxnoniae' E.coli which produce ESBLs were slightlystrOnger than Mezlociline, and showed lower Synrgism, which were consistent with theresults of suscePtibility tCst in vitrO. There was no significan difference againstPaeruginosa between MZBT and MZL. ExcePt for RaerUginosa. E.coli. K.pneumoniaeWhich produce ESBLs, the peak SBAs of MZBT against others were mor than l:8.Therefore, it was exPected that the efficacy of MZBT is better than that of MZL. (3) Theanibacterial achvity stUdy showed that the MBC and MIC of MZBT were similap Whichmean MZBT was a bactericide.The suscePtibility of MZBT against xiebsiellapneumoniae and Escherichia coli was 92.4% and 80%, which is higher than MZL orother agellts. The MIC. of MZL against ESBLs was more than 64ug/ml, while that ofMZBT was 32/4 ug/ml. Although the suscePtibility rato of MZBT was higher than that ofMZL, it was not higher than cefomycin. carbaPenems. The accumulative inhibiting curveshowed that the accurnlative inhibition rate of MZBT was higher than that of MZL atalmost every concentration.(4) The results showed that the cure rate was 68.75%, theefficacy fatC was 98.44%,the bacterial clearance was 89.09%, While the cure rates andefficacy rates in the contrOl grouP were 56.25% and 84.38%, and the bacterial clearancerate was 87.93%, There were no sighficat difference bdeeen the tWo grOuPs no seriousadVerse drug reactions of MZBT were observed in the clinical trial.CONCLUSION The anibacterial activity of MZBT against producing 6 -lactamaseK.pneumoniae and E.coli is better than that of MZL. MIC,,' MIC.. MICg of MZBT is7lower than that of MZL, Which su...