Effect and Mechanism of Fuzheng Touxie Prescription on Immune Homeostasis of Drug-resistant Pseudomonas aeruginosa Lung Infection Rats / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Fuzheng Touxie prescription （FZTX） on the immune homeostasis of drug-resistant <italic>Pseudomonas aeruginosa</italic> lung infection in rats at different time points. Method:A total of 168 rats were divided into a blank group （<italic>n</italic>=8），a model group （<italic>n</italic>=40），a Touxie （TX） group （<italic>n</italic>=40），an early Fuzheng （FZ） group （<italic>n</italic>=40）， and a delayed FZ group （<italic>n</italic>=40）. The blank group was given distilled water by gavage， the model group was given distilled water by gavage after infection，the TX group was given clear heat and penetrate evil drug free decoction granules（3.5 g·kg^-1） by gavage after infection， the early FZ group was given Fuzheng Touxie whole formula free decoction granules（10.75 g·kg^-1） by gavage after infection， the delayed FZ group was given clear heat and penetrate evil drug free decoction granules by gavage after infection， on the third day plus Fuzheng drug free decoction granules［（3.5+10.75） g·kg^-1］ by gavage， the three treatment groups were gavaged twice a day， 2 mL each time .Each drug treatment group was divided into five groups according to five time points （3 h，1 d，3 d，5 d， and 7 d）， with eight rats in each group. The levels of tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>），high mobility group protein 1（HMGB1），interleukin-10（IL-10）， and tumor necrosis factor -<italic>α</italic>-induced protein-8-like2 （TIPE2） were measured by enzyme-linked immunosorbent assay （ELISA）， and HMGB1 protein expression level by Western blot. Result:At 3 h，the TNF-<italic>α</italic> content in the drug treatment groups was higher than that in the blank group and the model group （<italic>P</italic><0.05）. At 3 d，the TNF-<italic>α</italic> content in the early FZ group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05） and the TX group （<italic>P</italic><0.05）. At 1 d，the HMGB1 content in the TX group and the delayed FZ group was higher than that in the model group （<italic>P</italic><0.05）. At 5 d，the HMGB1 content was lower in the delayed FZ group than in the model group （<italic>P</italic><0.05）. At 7 d，HMGB1 protein expression in the model group was higher than that in the blank group （<italic>P</italic><0.05） and the early FZ group （<italic>P</italic><0.05）. At 3 d，the IL-10 content was significantly higher in both the early FZ group and the delayed FZ group than that in the model group （<italic>P</italic><0.05）. At 5 d，the IL-10 content was higher in the early FZ group than that in the TX group （<italic>P</italic><0.05）. At 7 d，the IL-10 content in the early FZ group and the delayed FZ group was lower than that in the TX group （<italic>P</italic><0.05）. At 5 d，the TIPE2 content in the early FZ group was lower than that in the model group （<italic>P</italic><0.05）. At 7 d，the TIPE2 content in the TX group and the delayed FZ group was lower than that in the model group （<italic>P</italic><0.05）. Conclusion:FZTX or modified prescription can promote the inflammatory response to eliminate pathogenic bacteria in the early stage and suppress the inflammatory response in the late stage to avoid the inflammatory cascade effect and lung tissue damage，indicating that Fuzheng drugs have an important role in maintaining the immune homeostasis of the body after infection.

Effect of Tanreqing Injection and Antibiotics on Multi-drug Resistant Pseudomonas aeruginosa Efflux Pump / 中国实验方剂学杂志

Objective:To study the interaction between Tanreqing injection and commonly used antibiotics against multi-drug resistant Pseudomonas aeruginosa (MDR-PA) and the effect on bacterial efflux pump. Method:Antibiotic susceptibility test was performed with bacteria. Paper diffusion method (Kirby-Bauer, KB) combined with efflux pump inhibitor (50 mg·L-1) was used to measure the diameter of the inhibition zone, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect gene expression of efflux pump Positive efflux pump strain. KB method was used to observe the changes of Tanreqing (final concentration 3 g·L-1) and antibiotics on the diameter of the zone of inhibition. Strains were co-cultured with Tanreqing and antibiotic sub-inhibitory concentrations for Real-time PCR detection. KB method was used to observe the effect of Tanreqing on the diameter of bacteriostatic ring after the continuous use of efflux pump-positive bacteria. Result:Two MDR-PA efflux pump-positive strains were identified and screened. Tanreqing has synergistic antibacterial effect with aloxicillin, aztreonam, meropenem, ceftazidime, cefoperazone, and Shupushen. In inhibiting the expression levels of bacterial efflux pump genes, the four drugs were compared by the effect: cefoperazone>Tanreqing>ceftazidime>Shupushen. After Tanreqing continued to act on efflux pump-positive strains, it could have a better effect in combination with ceftazidime, cefoperazone, and Shupushen. Conclusion:Tanreqing, ceftazidime, cefoperazone, and Shupushen can reduce the drug resistance of bacteria by down-regulating the expressions of bacterial efflux pump genes, and reducing the clinical dose of antibiotics, and thus play a bacteriostatic effect.

Pharmacological Care for One Case of Patient with Multiple Drug-resistant Pseudomonas Aeruginosa Spsis Treated with Amikacin / 中国药师

Clinical pharmacists performed pharmaceutical care for one case of patient with multiple drug-resistant pseudomonas aeruginosa sepsis, assisted doctors in formulating anti-infective drug treatment plans and adjusted the regimen according to the results of bacterial culture and drug susceptibility combined with renal function of the patient. The participation of clinical pharmacists in clinical treatment practice ensured the safety and effectiveness of the patient's medication, avoided the occurrence of adverse drug reactions, and finally controlled the infection and improved the condition.

Pharmaceutical Care for One Case of Intervertebral Space Infection with Multiple Drug Resistant Pseudomonas Aeruginosa / 中国药师

Objective:To share a drug treatment experience for multiple drug resistant Pseudomonas aeruginosa.Methods:A retrospective analysis of the pharmaceutical care participated by clinical pharmacist for one case of intervertebral space infection with multiple drug resistant Pseudomonas aeruginosa was carried out.Results:Pharmacists participated in the whole treatment process,made the combined antimicrobial regimen (fosfomycin + ceftazidime + ciprofloxacin),and adjusted the time sequence.As a result,satisfactory curative effect was obtained.Conclusion:The infection with multiple drug resistant Pseudomonas aeruginosa may be treated with the three-drug therapy.Clinical pharmacists can play a positive role in the treatment of complicated infections.

Study on the anti-bacteria effects of polymyxin B combined with meropenem against pan-drug-resistant pseudomonas aeruginosa / 中国生化药物杂志

Objective To evaluate the anti-bacteria effects of polymyxin B combined with meropenem against 30 strains pan-drug resistant pseudomonas aeruginosa that separated in clinic. Methods The minimal inhibitory concentration (MICs) of 30 strains pan-drug resistant pseudomonas aeruginosa after treated with polymyxin B and meropenem as single-use or combination use were determined by both microdilution method and checkerboard method. The FIC index was calculated, then the type of combination effect was determined according to FIC index, which was used to determine whether there was synergistic or antagonistic effects. Results The MICs of pan-drug resistant pseudomonas aeruginosa were reduced significantly after polymyxin B combined with meropenem when compared with single-use. The percentages of the FIC index that less than 0.5 and the index between 0.5 and 1 were 60%and 30%respectively. Conclusion The results indicate that the combinations of polymyxin B with meropenem have good synergistic and additive effects against pan-drug resistant pseudomonas aeruginosa, there is no antagonism.

Genes of ?-Lactamase in Pan-drug Resistant Pseudomonas aeruginosa and Phylogenetic Analysis / 中华医院感染学杂志

OBJECTIVE To investigate the presence of ?-lactamase genes in pan-drug resistant Pseudomonas aeruginosa (PDRPA),and the redateness in PDRPA. METHODS The genes of 21 kinds of resistance were detected by polymerase chain reaction and phylogenetic analysis. RESULTS In 33 strains of PDRPA,the positive rates of blaTEM,blaOXA-10cluster,blaPER,blaGES,blaCARB,intⅠ1 and merA were 48.5%,45.5%,33.3%,21.2%,15.2%,78.8% and 69.7%,respectively. There were clone transmitted phenomena. CONCLUSIONS There are very high positive percentages of blaTEM,blaOXA-10cluster,blaPER,blaGES,blaCARB,intⅠ1 and merA genes in PDRPA. The PDRPA can induce clone transmitted hospital infection.

Genes of 16S rRNA Methylase and Aminoglycoside-modifying Enzymes in Pan-drug Resistant Pseudomonas aeruginosa / 中华医院感染学杂志

OBJECTIVE To investigate mechanisms of aminoglycoside resistance in pan-drug resistant Pseudomonas aeruginosa(PDRPA).METHODS The 11 genes of 16S rRNA methylase and aminoglycoside-modifying enzymes were detected by polymerase chain reaction(PCR) and verified by DNA sequencing.RESULTS In 33 strains of PDRPA,the positive rates of rmtB,aac(3)-Ⅱ,aac(6′)-Ⅰb,aac(6′)-Ⅱ,ant(3″)-Ⅰ and ant(2″)-Ⅰ were 42.4%,51.5%,42.4%,57.6%,48.5% and 63.6%.A total of 32 strains identified aminoglycoside modified genes,one strain aminoglycoside-modifying enzyme gene did not discovered,but rmtB positive.CONCLUSIONS The aminoglycoside resistance mechanisms of the PDRPA are the production of 16S rRNA methylase and aminoglycoside-modifying enzymes related.

Related Factors of Multi-drug Resistant Pseudomonas aeruginosa Infection / 中华医院感染学杂志

OBJECTIVE To evaluate the risk factors, therapy and prognosis of multi-drug resistant Pseudomonas aeruginosa infection. METHODS We made retrospective study of multi-drug resistant P. aeruginosa infection cases from Jan 2000 to Dec 2004 proved by samples tests. RESULTS Thirty four cases were infected by multi-drug resistant P. aeruginosa, 29 cases were with hospital infection. Among the 34 cases infected by multi-drug resistant P. aeruginosa, the mortality was 67.7%. There were 34 cases concomitant with 1-5 kinds of underlying diseases. There were 26 cases infected with more than 2 kinds of bacteria. CONCLUSIONS Multi-drug resistant P. aeruginosa infection mostly happens in old men, incorporated with underlying diseases and mixed bacterial infection .

Analyses on drug resistance phenotype of multi-drug resistant Pseudomonas aeruginosa and on antibacterial activity of combined antimicrobial agents / 解放军医学杂志

Objctive To investigate the zymogenic state and drug resistance of multi-drug resistant Pseudomonas aeruginosa (MDRP) for providing a laboratory basis of combined use of drugs against MDRP in clinical practice. Methods All isolates were isolated by routine procedures and identified by VITEK-2 automatic bacterial identification instrument. Following the CLSI instruction, doubling dilution in agar plates was performed for MIC detection. Results MDRP were 22.77% ( 86.96% for sputum) from 101 strains Pseudomonas aeruginosa, which were isolated from clinical specimens. Positive rates of MDRP producing metallo-?-lactmases were 91.3%, positive rates for producing induced Ampc and plasmid Ampc ?-lactamase were 52.17% and 21.74%, respectively. The ratio between Meropenem and Imipenem higher then 1 was 34.78%. The bacterial inhibitory rates of Polymyxin B and Imipenem were zero, that of Amikaein and Ceftaxidime were 4.35%, that of Ciprofloxacin and Cefoperazone/sulbactam were 43.48%, that of Pazufioxacin and Piperacillin/Tazobactam were 21.74% and 26.07%, and that of Meropenem was 47.83%. The combined use of Cefoperazone/sulbactam, Cefpirome, Piperacillin/Tazobactam with Amikacin resulted in bacteriostatic rate of 65.2%, 47.8%, 43.5%, respectively. Conclusoins MDRP is main micro-organism found in respiratory tract specimens. Drug resistance of MDRP is related to multiple drug-resistant mechanisms. Clinicians should first select enzyme inhibitory-drug (Cefoperazone/sulbactam or Piperacillin/Tazohaetam) with Amikacin or Polymyxin B to treat clinical MORP infection, and re-adjust the type of antibiotics rationally according to patients' symptoms, phenotype of the drug-resistant pathogen, the results of drug susceptibility test, and the effect on the patients.