Isolation and Characterization of Carbapenem-Resistant Escherichia coli Carrying blaNDM and mcr-1 from Recurrent Urinary Tract Infection Patient.

Objective: The emergence of carbapenem-resistant E. coli (CRECO), leading to few antibacterial drugs available for CRECO infection. In this study, we report three carbapenem-resistant Escherichia coli (E. coli) isolates coproducing blaNDM and mcr-1 from patients with recurrent urinary tract infection (RUTI). Carbapenem-resistant E. coli strains, E55, E84, and E85, were isolated from the urine sample of RUTI patients. Methods: Antimicrobial susceptibility testing (AST) was conducted with VITEK-2 compact system and Kirby-Bauer (K-B) disk diffusion method. The ESBL test was detected by the disk diffusion method. The EDTA-modified carbapenem inactivation method (eCIM) and modified carbapenem inactivation method (mCIM) were performed for screening the carbapenemase. Multilocus sequence typing (MLST) was performed for molecular typing of the strains. The resistance genes were detected by PCR. Results: The three isolates were all susceptible to tigecycline and nitrofurantoin. The blaNDM-1, blaCMY-6, blaTEM-1 and blaCTX-M-1, mcr-1, and porin loss expression of outer membrane protein F (OmpF) were detected in E55, which was assigned to ST2. The E84 and E85 were identified as ST471 carrying blaNDM-5, blaCTX-M55, and blaTEM-1 and the quinsolone-resistant genes aac(6')-Ib-cr and mcr-1. Conclusion: To our knowledge, our study is the first to report carbapenem-resistant E. coli strains carrying blaNDM and mcr-1 from urine of the recurrent urinary tract infection patients. These E. coli strains carrying blaNDM and mcr-1 should be closely monitored.

Analysis of Antimicrobial Susceptibility in Bacterial Pathogens Associated with Urinary Tract Infections from Beijing Teaching Hospital in China, 2009-2017.

Objective: Since a urinary tract infection (UTI) is easy to relapse and difficult to treat, the antibiotic resistance rate has increased year by year in recent years. This study was to analyze the characteristics of the common pathogenic bacteria and the changes of antibiotic resistance in urinary system infection, so as to guide the standard use of antibiotics in a clinical urinary tract infection and control nosocomial infection effectively. Methods: A total of 5,669 strains of a urinary tract infection in the hospital from January 2009 to December 2017 were retrospectively analyzed. Bacterial identification and the antibiotic sensitivity test (AST) were analyzed by using a VITEK-2 Compact system. Results: Of the 5669 pathogens, 3,256 (57.44%) of the strains were Gram-negative bacteria (GNB), 1,474 (26%) were Gram-positive bacteria (GPB), and 939 (16.56%) were fungi. Resistant rates of ESBL-producing strains were all significantly different from non-ESBL-producing strains in Escherichia coli (p < 0.05). The resistance rate of ESBL-producing strains to ß-lactam antibiotics was all higher than that of non-ESBL-producing strains in Klebsiella pneumoniae (p < 0.05). The detection rate of vancomycin-resistantEnterococcus faecium and Enterococcus faecalis was 37.3% and 3.1%, respectively, and the detection rate of linezolid-resistantEnterococcus faecium and Enterococcus faecalis was 0.68% and 0%, respectively. The drug resistance rate of candida sp. to fluconazole, itraconazole, and voriconazole was 1.7%, 8.5%, and 3.4%, respectively. No amphotericin B-resistant strains were detected in the research. Conclusions: Among the 5669 strains isolated from urinary tract infection patients, GNB were the main pathogens. Escherichia coli was the major pathogen. The resistance rate of ESBLs-producingEscherichia coli was higher than that of non-ESBLs-producingEscherichia coli in general; meanwhile, ß-lactam/ß-lactamase inhibitors and carbapenems maintained good antimicrobial activity against Escherichia coli. The resistance rate of non-ESBLs-producingKlebsiella pneumoniae strains was significantly higher than that of ESBLs-producingKlebsiella pneumoniae strains, and drug resistance was more prominent; most of the antibiotic resistance rates were over 50%. The antimicrobial resistance rate of Enterococcus faecium was significantly higher than that of Enterococcus faecalis. There were rare linezolid-resistant strains. The antimicrobial resistance rate of imidazole to fungi was controlled less than 10%.

Mineral Phase Reconstruction and Separation Behavior of Zinc and Iron from Zinc-Containing Dust.

Zinc-containing dust can be found in ironmaking and steelmaking, and it is an important secondary resource of zinc. Zinc-containing dust from an electric furnace was used as a raw material to study the phase transformation behavior of the dust using a calcification roasting process and the zinc-iron separation behavior by using ammonia leaching. The zinc-bearing dust was mixed with CaO and roasted to transform the zinc ferrite into zinc oxide. The results showed that increasing the calcium oxide to dust ratio could promote the conversion of zinc ferrite to zinc oxide. When the calcium oxide ratio reached 60%, the peak of zinc ferrite in the calcined-roasted product in the zinc-containing dust basically disappeared. As the temperature increased, the zinc oxide grains increased but were still smaller than 10 µm. The calcined-roasted product was crushed and ground, and the zinc was leached by ammonia. A zinc-iron recovery rate of 86.12% was achieved by the ammonia leaching. The leachate could be used for zinc extraction by electrolysis. The leaching residue was mainly calcium ferrate, which could be used in sintering production. The proposed process may achieve on-site recovery of zinc-containing dust in steel-making plants.

Risk Factors for Mortality in Hospitalized Patients with Stenotrophomonas maltophilia Bacteremia.

Objective: Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen with high mortality. And it has intrinsic resistance to a number of antibiotics classes. In this study, we investigated risk factors for death due to S. maltophilia bacteremia. Methods: A retrospective cohort study was conducted at a tertiary-care hospital in Beijing, China. The patients from the hospital database with S. maltophilia bacteremia between January 2011 and December 2020 were investigated. Univariate and multivariate analyses were performed to identify factors associated with mortality. Results: 51 patients with S. maltophilia bacteremia were identified. The mortality rate was 37.3%. Based on the univariate analysis, pulmonary disease (P=0.019), chronic kidney disease (P=0.014), shock (P=0.002), foley catheter (P=0.011), the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P<0.001), procalcitonin (PCT) (P=0.045) and using antifungal agent (P=0.033) were significantly related to mortality. Based on the multivariate analysis, the APACHE II score (odds ratio [OR] =1.211; 95% confidence interval [CI]: 1.061, 1.382; P=0.005) was independent factor associated with mortality. S. maltophilia was the most susceptible to minocycline (94.7%), followed by trimethoprim and sulfamethoxazole (TMP/SMX, 92.2%). Conclusion: Our findings suggested that the APACHE II score was a significantly independent predictor in S. maltophilia bacteremia patients. The use of TMP/SMX or minocycline might be the first choice for the treatment of S. maltophilia bacteremia.

A Boron Dipyrromethene-Based Fluorescence 'OFF-ON' Probe for Sensitive and Selective Detection of Palladium(II) Ions and Its Application in Live Cell Imaging.

A novel boron dipyrromethene (BODIPY)-based fluorescent probe BDP-Pd was designed and synthesized. Upon coordination with Pd2+ , the emission of the probe at 508 nm significantly increased, showing an 'OFF-ON' fluorescence response. The complexation of BDP-Pd with Pd2+ in both acetonitrile and aqueous solution were then studied by absorption and fluorescence spectra. The binding stoichiometry between the probe and Pd2+ was found to be 1 : 2, and the binding constant was determined to be 8.5×1010  M-2 and 8.2×1010  M-2 in acetonitrile and aqueous solution, respectively. The probe exhibited a detection limit as low as 0.72 ppb toward Pd2+ with no obvious interference from up to 21 species of common metal ions, suggesting BDP-Pd as a sensitive and selective fluorescent probe for Pd2+ detection. The fast fluorescence 'OFF-ON' phenomenon of the probe upon coordination with Pd2+ ions could be easily observed by a hand-hold UV lamp under naked eye in solution as well as on homemade test trips. Density functional theory (DFT) calculations were carried out to give the optimized structure of complex BDP-Pd : 2Pd2+ and rationalize the detection mechanism through a prohibited intramolecular photoinduced electron transfer (PET) process. The bio-imaging application of the probe was investigated and it showed excellent cell permeability for fluorescent imaging of Pd2+ ions in A549 human non-small cell lung cancer cells.

Dissemination of cfr-mediated linezolid resistance among Staphylococcus species isolated from a teaching hospital in Beijing, China.

Objective The aim of the present study was to report the dissemination of cfr and fexA genes mediated by linezolid resistance among Staphylococcus species. Methods Three methicillin-resistant staphylococci that were collected from a teaching hospital in Beijing were identified as linezolid-resistant. These three staphylococci were Staphylococcus aureus, S. haemolyticus, and S. cohnii. Mutations in domain V of 23S ribosomal RNA, ribosomal proteins, and the cfr, fexA, and optrA genes were analysed. Results The three isolates had no mutations of 23S ribosomal RNA, but showed mutations in the cfr and fexA genes. Mutations in the gene for ribosomal protein L3, which resulted in the amino acid exchanges Gly108Glu, Ser158Phe, and Asp159Tyr, were identified in S. cohnii X4535. Conclusions This is the first report of the cfr gene in clinical linezolid-resistant methicillin-resistant S. aureus isolated from Beijing. L3 mutations coupled with the cfr and fexA genes may act synergistically. Potential transmissibility of this agent, even without prior exposure to linezolid, may have serious epidemiological repercussions.

Palladium-Catalyzed Imidoylative Cyclization of Tryptophan-Derived Isocyanides: Access to ß-Carbolines.

A palladium-catalyzed imidoylative cyclization of ethyl-3-(1H-indol-3-yl)-2-isocyanopropanoates, derived from readily available tryptophan, to afford ß-carboline derivatives has been developed. The reaction proceeds smoothly under mild conditions through sequential isocyanide insertion, intramolecular C-H imidoylation, and aerobic dehydrogenative aromatization with a decent substrate scope. This method provides a general approach for the synthesis of molecules containing the ß-carboline fragment.

A model for predicting nosocomial carbapenem-resistant Klebsiella pneumoniae infection.

Mortality associated with infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) is high and the infections need to be predicted early. The risk factors for CR-KP infection are heterogeneous. The aim of the present study was to construct a model allowing for the early prediction of CR-KP infection. Nosocomial infections due to K. pneumoniae were evaluated retrospectively over a 2-year period. The case cohort consisted of 370 inpatients with CR-KP infection. For each case enrolled, two matched controls with no CR-KP infection during their hospitalization were randomly selected. Matching involved month of admission, ward, as well as interval days. The Vitek 2 system was used for identification of isolates and antimicrobial susceptibility testing. General linear model with logistic regression was used to identify possible risk factors. The predicted power of the model was expressed as the area under the receiver-operating characteristic curve. Age, male gender, with cardiovascular disease, hospital stay, recent admission to intensive care unit, indwelling urinary catheter, mechanical ventilation, recent ß-lactam-ß-lactamase inhibitors, fourth-generation cephalosporins and/or carbapenems therapy were independent risk factors for CR-KP infection. Models predicting CR-KP infection developed by cumulative risk factors exhibited good power, with areas under the receiver-operating characteristic curves of 0.902 [95% confidence interval (CI), 0.883-0.920; P<0.001] and 0.899 (95% CI, 0.877-0.921; P<0.001) after filtering by age (≥70 years). The Yonden index was at the maximum when the cumulative risk factors were ≥3 in the two prediction models. The results show that the prediction model developed in the present study might be useful for controlling infections caused by CR-KP strains.

Pd-Catalyzed C(sp2)-H carbonylation of 2-benzylpyridines for the synthesis of pyridoisoquinolinones.

An efficient synthesis of pyridoisoquinolinones, through Pd-catalyzed carbonylative annulation of 2-benzylpyridines, has been developed. The pyridinyl moiety in the substrate acts as both a directing group and an internal nucleophile for sp2 C-H activation and pyridocarbonylation. The ready availability of 2-benzylpyridines as well as the operational practicality makes this transformation potentially useful for the synthesis of analogues of protoberberine alkaloids.

Copper-mediated C(sp(3))-H azidation with Me3SiN3: synthesis of imidazoles from ketones and aldehydes.

The efficient construction of 2,4,5-trisubstituted imidazoles, through a copper-mediated three-component reaction involving ketones, aldehydes, and Me3SiN3, has been developed. During the process, 4 C-N bonds were formed sequentially. Experimental results and DFT calculations suggested that azidation of the alpha methylene group of the ketone was the key C-N bond-forming step.

Palladium-catalyzed intramolecular C(sp(2))-H imidoylation for the synthesis of six-membered N-heterocycles.

A new strategy for the construction of phenanthridine and isoquinoline scaffolds, starting from arenes containing a pending isocyanide moiety under palladium catalysis, has been developed. This process involves sequential intermolecular isocyanide insertion to an aryl palladium(II) intermediate and intramolecular aromatic C-H activation as key steps. Alkyl palladium(II) intermediate lacking ß-hydrogen is also applicable to this reaction, generating unique bisheterocyclic scaffolds with three C-C bonds being formed consecutively.

Copper-catalyzed C(sp2)-H amidation with azides as amino sources.

A copper-catalyzed C-H amidation process, with azides as amino sources under oxidant-free conditions, has been developed. When N-heterocycles were employed as directing groups, sulfonylazide and benzoylazide could be used as amidating reagents to provide corresponding N-arylamides. When amidines or imine were used, tandem C-N/N-N bond formation occurred to afford indazole derivatives in one pot.