Study On Drug Resistance Of Multiple Drug-resistant Gram-negative Bacilli And Anti-infective Therapy

PartⅠStudy on the epidemic state of extended-spectrumβ-lactamase producing Escherichia coli and anti-infective therapyObjective : To investigate the epidemiological status of extended-spectrum-βlactamase (ESBL) producing Escherichia coli and the drug resistance;To explore the in vivo activities of ceftazidime with susceptibility in vitro in rats with experimental pneumonia caused by ESBLs-producing strain of Escherichia coli, for the clinical application of ceftazidime treatment ESBLs-producing strains of infection provide experimental basis. Methods: 1)Make a retrospective analysis for the prevalence of ESBLs-producing Escherichia coli and drug resistance from 2003 to 2006; 2)With intratracheal instillation method, 3 Escherichia coli strains isolated from this hospital were used to establish neutropenic- rat pneumonia model. According to the bacteria strains, 132 adult female Sprague-Dawley rats were separated into three group: groupⅠ(82017, non- ESBLs -producing strains),groupⅡ(81424, ESBLs -producing strains),groupⅢ(31704, ESBLs -producing strains), Each group were further divided into five sub-groups: one control group and four groups treated with ceftazidime(200,400,600,800 mg/kg per 12h); Therapy was started 16 hours after bacterial inoculation and continued for 3 days; Plasma samples were collected at 4.8and 8.4 hours afterdrug administration, ceftazidime concentrations in serum were determined by using high-pressure liquid chromatography assays; The efficacies were evaluated 96 hours later by the survival rate and the viable bacterial counts of the lungs. Simultaneously takes 10 times of dilutions the lung tissue refining fluids 100μl, Inoculated with the non- ceftazidime and 2×MIC, 4×MIC-MH-agar plate, the selection of resistance mutations. Results: 1)The incidences of ESBLs -producing strains in Escherichia coli were16.1%～53.8% and were increasing year on year;the resistant rate of ESBLs -producing strains against most antibiotics was significantly higher than that of non- ESBLs -producing strains(P<0.05). 2) The statistics show that on the whole of rats in each group the survival rate gradually increased with the dose increased, but the difference was not statistically significant (p> 0.05); The bacterial counts of the lungs was reducted in all CAZ subgroup.The bacterial counts of the lungs in CAZ(400,600,800mg/kg) subgroup of groupⅠand groupⅡ, CAZ(600,800mg/kg) subgroup of groupⅢshowed significant reduction compared with control group (p <0.05);Compared with groupⅠ, the bacterial counts of the lungs in groupⅡhave no significant difference(p>0.05), however, have significant difference in groupⅢexcept CAZ200mg/kg subgroups(p<0.05).In groupⅠ, the bacterial counts of the lungs of CAZ400mg/kg subgroup showed significant reduction compared with CAZ200mg/kg and there have no significant difference in the rest adjacent subgroup comparison.3) PK / PD analysis showed that the bacterial counts of the lungs of showed significant reduction when % T> MIC exceed 70%compared with below 40%(p<0.05). 4) each group of three days from the lung tissue of a higher frequency of mutant strains resistant. However, there have no significant difference between subgroups. Conclusion:The incidences of ESBLs -producing strains was higher in Escherichia coli and were multi-drug resistant; Ceftazidime showed good therapeutic effect on pneumonia caused by ESBLs-producing E. coli which was susceptible to ceftazidime in vitro, but in the course of treatment necessary to monitor the blood concentration, according to the results of blood concentration administration adjustment programmes to achieve the best anti-infection treatment. PartⅡDrug resistance and genetic homology of imipenem resistant Acinetobacter baumanniiObjective : To investigate the drug resistance of imipenem resistant Acinetobacter baumannii isolated from our hospital. To explore the relationship between imipenem resistant Acinetobacter baumannii and ESBLs-producing bacteria isolation in hospital infection,To characterize the genetic homology of imipenem resistant Acinetobacter baumannii isolated from our hospital. Methods: The susceptibility testing was performed with Vitek-32and Kirby-Bauer(KB)method;The relationship between imipenem resistant Acinetobacter baumannii and ESBLs-producing bacteria was analysed by software SPSS11.5.Using repetitive sequence based polymerase chain reaction (rep-PCR) technique to make typing of 33 Imipenem resistant Acinetobacter baumannii from sep 2006 to jul 2007,and make comparisons between rep-PCR typing and drug-resistant spectrum typing. Results: 1) The drug resistance rate other antimicrobial agents was higher than 54.5% except Cefoperazone-sulbactam was less than 10%. 2)In recent 7 years, significant positive correlations were found between the isolation ratio of ESBLs-producing Escherichia coli and Imipenem resistant Acinetobacter baumannii(rs=0.822, P=0.012). 3)There were 3 genotypes (E1～E3)rep-PCR in 33 Imipenem resistant Acinetobacter baumannii isolates with rep-PCR ,mainly including type E1 of 27strains,amounting to81.8%; which were divided intoⅠ～Ⅵtypes according to drug-resistant spectrum typing. mainly including typeⅠof 18 strains,amounting to54.5%. Conclusion: Isolates of imipenem resistant Acinetobacter baumannii pose a serious situation of multidrug-resistance.The significant correlations were found between isolation ratio of ESBLs-producing Escherichia coli and Imipenem resistant Acinetobacter baumannii; The Isolates of imipenem resistant Acinetobacter baumannii outbreak of nosocomial infection is due to transmission of the same strains among different individuals.