Background Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018. Methods We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. Results For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 μg/mL vs. 8 μg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 μg/mL vs. 64 μg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. Conclusions AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

Little is known about the epidemiology and carbapenem-resistance determinants of carbapenem-resistant K. aerogenes (CRKA) isolated from a single medical center. The present study was initiated to characterize the molecular epidemiology and the carbapenemresistance mechanisms of CRKA isolated during 2012-2018 from a teaching hospital in southwest China, and to investigate the risk factors and clinical outcomes of CRKA infections as well. Methods: Pulsed-field gel electrophoresis (PFGE) was employed for epidemiological analysis. PCR amplification and DNA sequencing were used to examine the antibiotic-resistance determinants. Plasmids were extracted and characterized by PCR-based replicon typing and conjugation assays. In order to further investigate the risk factors and clinical outcomes of CRKA infections, a retrospective case-control study was also performed. Results: PFGE analysis showed 32 different PFGE patterns among the 36 non-duplicated CRKA strains collected. Most of the isolates harbored multi-drug resistance (MDR) genes, including 2 (5.6%) carrying bla NDM-1 , 1 (2.8%) harboring bla KPC-2 , 13 (36.1%) carrying ESBL genes, 23 (63.9%) carrying ampC genes, 34 (94.4%) carrying quinolone resistance determinants (QRD) genes and 9 (25%) carrying aminoglycoside resistance determinants (ARD) genes. The outer membrane porins, OmpE35 and OmpE36, were, respectively, lost in 4 and 2 isolates. The efflux pump inhibition experiments were positive in 25 (69.4%) of the CRKA strains. Multivariate analysis indicated that hypo-albuminaemia, invasive procedures, and carbapenem exposure were independent risk factors for acquiring CRKA infections. Conclusion: No clonality relationship was identified among most of the 36 CRKA isolates. The over-expression of ESBLs and AmpC coupled with the efflux pumps contributed to carbapenem resistance in K. aerogenes. Additionally, this is the first report of CRKA isolate co-harboring bla NDM-1 , bla CTX-M-15 , bla EBC , bla ACC , acc (6ʹ)-Ib, armA, qnrD and loss of OmpE36 in China. Hypo-albuminaemia, invasive procedures and carbapenem exposure were associated with acquisition of CRKA infections.

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Aim: We aim to depict the clinicoepidemiological and molecular information of carbapenem-resistant Enterobacteriales (CRE) in Chongqing, China.Methods: We performed a prospective, observational cohort study, recruiting inpatients diagnosed with CRE infections from June 1, 2018, to December 31, 2019. We carried out strain identification and molecular characterization of CRE. eBURST analysis was conducted to assess the relationships among the different isolates on the basis of their sequence types (STs) and associated epidemiological data using PHYLOViZ. Clinical parameters were compared between the carbapenemase-producing Enterobacteriales (CPE) and non-CPE group.Findings: 128 unique CRE isolates from 128 patients were collected during the study period: 69 (53.9%) CPE and 59 (46.1%) non-CPE. The majority of CPE isolates were blaKPC-2 (56.5%), followed by blaNDM (39.1%) and blaIMP (5.8%). Klebsiella pneumoniae carbapenemase (KPC)–producing clonal group 11 Klebsiella pneumoniae (K. pneumoniae) was the most common CPE. Antibiotic resistance was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE infection were ICU admission and hepatobiliary system diseases. Although, there was no significant difference in desirability of outcome ranking (DOOR) outcomes between the two groups. At 30 days after index culture, 35 (27.3% ) of these patients had died.Conclusion: CRE infections were related to high mortality and poor outcomes, regardless of CRE subgroups. CPE were associated with prolonged ICU stays and had different clinical and microbiological characteristics than non-CPE. The identification of CPE/non-CPE and CRE resistance mechanisms is essential for better guidance of the clinical administration of patients with CRE infections.

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is a tumor suppressor in several cancers, such as glioma, prostate cancer and esophageal cancer. However, the role of MEG3 in hepatocellular carcinoma (HCC) and the related molecular mechanisms are not well understood. The present study aimed to determine the biological function of MEG3 in regulating HCC cell viability, apoptosis and migration. In addition, the interaction between MEG3, microRNA (miR)-9-5p and Midkine (MDK), and the activation of the phosphoinositide-dependent kinase (PDK)/AKT pathway in HCC cell line MHCC-97L were examined. Luciferase reporter assays, reverse transcription-quantitative PCR and western blotting were used to determine the interaction between MEG3, miR-9-5p and MDK and the activation of the PDK/AKT pathway. Cell viability was determined by the CCK8 assay and the cell cycle analysis using flow cytometry analysis. Cell apoptosis was examined by flow cytometry analysis and caspase 3/9 activity. Wound healing assays and western blotting were used to investigate cell migration. The present study demonstrated that MEG3 suppressed HCC cell viability and migration, and induced cell apoptosis. In addition, it was also found that MEG3 targets the miR-9-5p/MDK axis and modulates the PDK/AKT pathway in HCC. In conclusion, the findings of the present study demonstrated that lncRNA MEG3 affects HCC cell viability, apoptosis and migration through its targeting of miR-9-5p/MDK and regulation of the PDK/AKT pathway. The MEG3/miR-9-5p/MDK axis may be a potential therapeutic target in HCC.