| Multidrug-resistant Acinetobacter baumannii and Methicillin-resistance S.aureus(MRSA) are the most common pathogenic bacteria in Intensive Care Unit(ICU). Itis highly pathogenic. In recent years, as a result of the abuse of antibiotics, they hasbecome more resistant to antibiotics, which can cause treatment failure and an increasedmortality. Faced with the rapid spread of drug-resistant bacteria, the grim situation thatmortality rates of infectious disease continue to climb, governments in different countrieshave made controlling the harm caused by infection of drug-resistant bacteria focus ofattention, and the development of new strategies to effectively control drug-resistantbacterial infections have become imperative aim of research for us. The main contents aredivided into three parts as follows:Part1: Distribution and drug resistance of common pathogenic bacteria in the ICUof our hospital Objective: To investigate the species, distribution and drug resistance of thepathogenic bacteria submitted from all special ICUs of our hospital so as to guide thereasonable clinical use of antibiotics.Methods: A retrospective analysis was performed for4116strains of pathogensisolated from various infectious samples from the patients who enrolled the ICUs from Jan2009to Dec201l.Results: Of4116strains of pathogens isolated, there were2791(67.81%) strains ofgram-negative bacteria,979(23.78%) strains of gram-positive bacteria, and346(8.41%)strains of fungi. The top5predominant species of pathogens were Acinetobacterbaumannii(802strains,18.48%), Staphylococcus aureus (699strains,16.98%),Pseudomonas aeruginosa (640strains,15.55%), Klebsiella pneumonia (468strains,11.37%), Escherichia coli (303strains，7.36%).The positive rates of extended spectrumβ-lactamase-producing K.pneumoniae and E.coli were61.54%and68.65%, respectively.The MRSA strains accounted for91.42%among all the S.aureus isolates. The detectionrate of vancomycin-resistant Enterococcus ecium was4.09%,and no strains ofvancomycin-resistant S.aureus were found.Conclusion: The gram-negative bacteria are the main pathogens causing infections inthe ICUs. The results of drug susceptibility testing shows that the strains aremultidrug-resistant. It is necessary to choose the sensitive antibiotics and to strengthen thereasonable use of antibiotics on the basis of the result of drug susceptibility testing.Part2: A new way of treatment in a murine model of sepsis caused bymultidrug-resistant Acinetobacter baumanniiObjective: This study was to investigate the synergistic activity of meropenemcombined with other antibiotics in vitro and in vivo.Methods: Checkerboard assay and time-kill assay were performed to study the combinationeffects in vitro. For the animal model, a murine sepsis model injected with inoculumsintraperitoneally was used to study the combination effects in vitro.Results: Susceptibility test showed that all the twelve strains in this study were resistant to most of the antibiotics except rifampicin. In combination, meropenem plus rifampicin exhibitedsynergistic activity against six of twelve strains. In the sepsis model, meropenem monotherapy hadno therapeutic effect in this model while it can enhance the activity of rifampicin in both survivalrate and bacterial clearance from blood. Moreover, combination therapy significantly reducedplasma IL-6levels compared with rifampicin monotherapy.Conclusion: These data above showed that there was synergistic activity betweenmeropenem and rifampicin against multidrug-resistant Acinetobacter baumannii both in vitro andfor experimental model of sepsis.Part3: Study of PK/PD profle in plasma and site of infection in an experimentalpneumonia model caused by methicillin-resistant Staphylococcus aureusObjective: The aim of this study was the evaluation PK/PD profle ofvancomycin,linezolid and Tigecycline in plasma and site of infection in an experimentalpneumonia model caused by methicillin-resistant Staphylococcus aureusMethods: In vitro activities of vancomycin, linezolid and Tigecycline were testedusing Checkerboard synergy tests. Experimental pneumonia in neutropenic BALB/c micewas achieved using one clinical MRSA strains, MRSA16(vancomycin, linezolid andTigecycline MICs of1,2and0.25mg/L, respectively). In vivo dosages were150mg/kgvancomycin,90mg/kg linezolid and15mg/kg Tigecycline.Results: Survival rates in controls, and in the groups treated with vancomycin,linezolid and Tigecycline were46.3%,73.3%,93.3%,100%, respectively. Finally, therespective bacterial lung concentrations (log10cfu/g) were7.57±0.59,3.21±1.78,1.53±1.36,1.04±1.19for MR16. The ratios of the AUC0-24/MIC in plasma and lung tissues were302.63、138.24；231.27、90.83；7.56、21.88。Conclusion: This study showed that for MRSA pneumonia, linezolid and tigecyclineeither in the survival of mice or lung tissue bacterial clearance rate better than vancomycin,and tigecycline distribution in the lung tissue of the best. |
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