Glabridin Functions as a Quorum Sensing Inhibitor to Inhibit Biofilm Formation and Swarming Motility of Multidrug-Resistant Acinetobacter baumannii.

Objective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study. Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method. Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512-1024 µg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found. Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.

Acquisition of Tigecycline Resistance by Carbapenem-Resistant Klebsiella pneumoniae Confers Collateral Hypersensitivity to Aminoglycosides.

Tigecycline is a last-resort antibiotic for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to broaden our understanding of the acquisition of collateral hypersensitivity by CRKP, as an evolutionary trade-off of developing resistance to tigecycline. Experimental induction of tigecycline resistance was conducted with tigecycline-sensitive CRKP clinical isolates. Antimicrobial susceptibility testing, microbial fitness assessment, genotypic analysis and full-genome sequencing were carried out for these clinical isolates and their resistance-induced descendants. We found that tigecycline resistance was successfully induced after exposing CRKP clinical isolates to tigecycline at gradually increased concentrations, at a minor fitness cost of bacterial cells. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) found higher expression of the efflux pump gene acrB (5.3-64.5-fold) and its regulatory gene ramA (7.4-65.8-fold) in resistance-induced strains compared to that in the tigecycline-sensitive clinical isolates. Stable hypersensitivities to aminoglycosides and other antibiotics were noticed in resistance-induced strains, showing significantly lowered MICs (X 4 - >500 times). Full genome sequencing and plasmid analysis suggested the induced collateral hypersensitivity might be multifaceted, with the loss of an antimicrobial resistance (AMR) plasmid being a possible major player. This study rationalized the sequential combination of tigecycline with aminoglycosides for the treatment of CRKP infections.

[Antimicrobial resistance characteristics of and disinfectant-resistant gene distribution in Staphylococcus aureus isolates from male urogenital tract infection].

OBJECTIVE: To study the antibiotic- and disinfectant-resistance features of and disinfectant-resistant gene distribution in Staphylococcus aureus (Sa) isolated from the urogenital tract of male patients with urogenital tract infection (UTI). total of 152 Sa isolates were collected from the urethral discharge specimens from male UTI patients. The minimum inhibition concentration (MIC) of antimicrobial agents and disinfectants commonly used against Sa were tested by standard ager dilution; the methicillin-resistant Sa (MRSA) isolates detected by cefoxitin disk diffusion and mecA gene amplification; Staphylococcal cassette chromosome mec (SCCmec) genotyping performed by multiplex PCR; the disinfectants gene qac (quaternary ammonium compound) amplified by PCR; and the clonal relatedness of qacA/B-positive MRSA isolates investigated by pulsed-field gel electrophoresis (PFGE). RESULTS: Out of the 152 Sa isolates, 91 (59.9%) were found to be MRSA. SCCmec genotyping showed SCCmec V to be the main type, accounting for 63.7% (58/91), with 8 (8.8%) isolates of SCCmec I, 2 (2.2%) isolates of SCCmec II, 19 (20.9%) isolates of SCCmec III, and 4 (4. 4%) isolates of SCCmec IV. The Sa isolates exhibited high rates of non-susceptibility to penicillin (95.4%) , erythromycin (72.4% ) , ciprofloxacin (42. 8%), and levofloxacin (44.7%), and a fairly high sensitivity to nitrofurantoin, teicoplanin, linezolid, and vancomycin. The MIC in the Sa isolates was 0. 25 -16 microg/ml for chlorhexidine; MIC50 and MIC90 were 2.0 and 4.0 microg/ml respectively for MRSA strains and both 1.0 microg/ml for MSSA strains. Out of the 152 Sa isolates, 72 (47.4%) harbored the qacA/B gene, 6 (3.9%) the smar (qacC + qacD) gene, 9 (5.9%) the qacE delta 1 gene, and 2 (1.3%) the qacH gene, but no qacG and qacJ genes were detected. PFGE analysis showed that the qacA/B-positive MRSA isolates were distributed CONCLUSION: Clinical Sa isolates exhibited varied degrees of resistance to commonly used antibiotics, and in a polyclonal manner. some showed a robust tolerance to chlorhexidine. The main disinfectant-resistant gene is qacA/B. Antimicrobial agents and disinfectants should be used rationally according to clinicians.

Impact of low versus conventional doses of chemotherapy during transcatheter arterial chemo-embolization on serum fibrosis indicators and survival of liver cancer patients.

OBJECTIVES: To explore the impact of low- vs conventional-dose chemotherapy via transcatheter arterial chemo-embolization (TACE) on serum fibrosis indicators and treatment efficacy of hepatocellular cancer patients (HCC). MATERIALS AND METHODS: Patients fulfilling the eligibility criteria were assigned to TACE in Group A (with low-dose chemotherapy) or Group B (conventional-dose chemotherapy). Four serum fibrosis related indicators, hyaluronic acid(HA), human pro-collagen type-III (hPC-III), laminin (LN), and collagen type-IV(IV-C) before TACE were compared with the values 7 days after TACE. The response rate and survival time were also compared between the two groups. RESULTS: Fifty patients with HCC were enrolled in this study, including 25 in Group A and 25 in Group B. No significant differences were detected between the two groups in the four indicators before TACE. After TACE, the value of the four serum indicators increased significantly in Group B. However, no significant differences regarding these four indicators were found in Group A after TACE. Significant differences were demonstrated between the two groups after TACE, but median survival time and 1 or 2 year overall survival rates did not differ (P>0.05). CONCLUSIONS: Low-, compared with conventional-dose chemotherapy exerts the same impact on the variation of fibrosis related indicators and has no influence on median survival time and survival rate after TACE in HCC patients.

Retrospective analysis of 56 patients with advanced gastric cancer treated with combination of intravenous and intra-arterial intensified neoadjuvant chemotherapy.

BACKGROUND: Pre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced gastric cancer. METHODS: A total of 56 histologically proven gastric cancer patients, who were considered to be stage II or higher with metastatic lymph nodes and with or without distant metastasis (T2-4, N1-3, and M0-1), were treated with a neoadjuvant chemotherapy. Patients received a combination of intravenous 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) on days 1-5, and intra-arterial etoposide (80 mg/m2) and cisplatin (80 mg/m2) on days 6 and 20. After two cycles of preoperative chemotherapy, patients with resectable tumors underwent laparotomy. RESULTS: All patients finished two cycles of chemotherapy. The overall response rate was 78.57% (44 cases), of which 7.14% (four cases) clinical complete response. Forty-six patients underwent resection, including 21 initially unresectable diseases. R0 resection rate for prechemotherapy resectable and unresectable diseases was 96.15% (25/26 cases) and 66.67% (20/30 cases), respectively. Pathological complete response was observed in 8.70% of patients. Toxicity was moderate and there were no chemotherapy-related deaths. With a median follow-up of 31 months (range 6-76 months), the 5-year survival rate for the whole group and patients with initially resectable tumors were 21.8% and 42.3%, respectively. The median survival for initially resectable and unresectable patients were 41 months (95%CI, 31.006-50.994) and 18 months (95%CI, 13.399-22.601; P<0.01), respectively. CONCLUSION: Preliminary results proved that the combined intensive chemotherapy was a safe and promising regimen for pre-operative treatment of advanced gastric cancer.

[Long-term results of TIPS, TIPS with CVO and combined TIPS and portal azygous disconnection for the treatment of portal hypertension].

OBJECTIVE: To analyze the long-term results of TIPS, TIPS with coronary vein occlusion (CVO) and combined TIPS and portal azygous disconnection for the treatment of portal hypertension and variceal bleedings. METHODS: Three hundreds and fifty-eight patients with portal hypertension were admitted because of variceal bleeding from July 1993 to May 2008. All patients were divided into 3 groups: 227 cases in group TIPS, 36 cases in TIPS and CVO group, 95 cases in combined TIPS and portal azygous disconnection group. The rates of successful operation, shunt patency, rebleeding, encephalopathy and survival were observed and compared by statistics methods. RESULTS: There were 349 cases (97.5%) underwent successful surgery and 9 cases with failure surgery. The rates of occluded shunts, encephalopathy, rebleeding, and death in early periods were 2.5%, 31.8%, 4.7% and 9.0% respectively. The rate of encephalopathy and death in group with TIPS were higher than in group with combined TIPS and portal azygous disconnection (P < 0.01). The rate of encephalopathy and death were 41.2% and 24.7% in 85 cases with emergency TIPS. During the follow-up 1 - 15 years, the rate of patency shunts in 12 and 24 months after operation was 74.0% and 48.1% respectively. The rate of 1-year patency shunts in group with combined TIPS and portal azygous disconnection was higher than in group with TIPS, TIPS and CVO (P < 0.01 and P < 0.05). The rebleeding in group with TIPS was higher than in group with combined TIPS and portal azygous disconnection (P < 0.01), and the survival rate in group with TIPS was lower than in group with TIPS and CVO, combined TIPS and portal azygous disconnection (P < 0.01 and P < 0.01). CONCLUSIONS: TIPS is an efficient therapy for portal hypertension with CVO, combined TIPS and portal azygous disconnection can improve the results of TIPS for portal hypertension.