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Background: OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has the potential to become the "third epidemic" of carbapenem-resistant Klebsiella strain after KPC-2 and NDM in China. We investigated the first outbreak of CRKP in the First Affiliated Hospital of Wenzhou Medical University. Methods: We collected 610 clinical isolates of CRKP from the First Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2020 and screened them by Polymerase Chain Reaction (PCR). The multilocus sequence typing and pulsed-field gel electrophoresis were used to determine the genetic relatedness of the strains. The antimicrobial susceptibility test was performed to determine the drug resistance of the clinical isolates. The molecular mechanism underlying carbapenem resistance was elucidated by performing PCR and conjugation experiments. The virulence potential of the strains was determined by the string test, detection of virulence-associated genes and capsular serotypes, and Galleria mellonella larval infection model. Results: Between September 2019 and May 2020, 26 OXA-232-producing CRKP were obtained from 12 patients in our hospital. Ten patients were hospitalized in the intensive care units (ICU) and the overall mortality of the inpatients involved in the outbreak was 50% (6/12). Epidemiological investigations reported that all the OXA-232-producing CRKP strains belonged to the sequence type ST15 and can be clonally transmitted among the inpatients in the ICU. All the strains had low virulence and were resistant to commonly used clinical antibiotics except for ceftazidime/avibactam, colistin, and tigecycline. The OXA-232-producing CRKP was sensitive to triclosan and chlorhexidine, and its eradication from our hospital can be achieved by the use of disinfectants in the ICU. Conclusion: In our study, OXA-232-producing CRKP isolates appeared to be clonally transmitted and the sequence type ST15 was responsible for the outbreak. Therefore, effective measurements for the infection control of CRKP are urgently needed to prevent its epidemic in the nearby region in the future. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in China. Methods: This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed. Results: A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2, a sequence type that has spread all over the world. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after positive blood culture, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline. Conclusions: BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option. [ABSTRACT FROM AUTHOR]

• Right-turning vehicle-pedestrian conflict assessment at intersection crosswalks. • Various behavior models are integrated to a simulation platform. • The frequency and severity of conflict can be represented by SSMs. • Large dimensions and turning angles result in undesirable safety performance. Frequent vehicle-pedestrian conflicts deserve special attention for safety assessment at intersections. This study helps verify how the simulation as an innovative approach can be utilized for right-turning vehicle-pedestrian conflict assessment at intersection crosswalks prior to implementation. Various behavior models such as vehicle turning path, turning speed, gap acceptance model and pedestrian behavior model, have been established. Through integrating the calibrated models into one simulation platform, the stochastic behavior of vehicles and pedestrians under different geometric layouts and operational conditions can be reproduced. Based on the field data collected by an unmanned aerial vehicle (UAV) at two urban intersections in Beijing, China, it was demonstrated through validation of surrogate safety measures (SSMs), i.e., Post Encroachment Time (PET) and vehicle passing speed at conflict points, that the simulation model can reasonably represent the frequency and severity of conflict occurrence at signalized crosswalks. The sensitivity analysis results indicated that large dimensions and turning angles of intersections tend to result in undesirable safety performance. [ABSTRACT FROM AUTHOR]

Increasing attentions have been paid to energy consumption problem due to ecology pressure. This has prompted a growing focus of policy design to explore the driving forces of energy consumption. As the biggest city in China, Shanghai ranks the 1st in economic aggregate in mainland China but faces greater energy shortage challenges than the other cities. In this study, we aim to investigate the energy consumption between 1990 and 2019 in Shanghai to facilitate the sustainable development of population, resources, and environment. Specifically, a hybrid approach coupling LMDI (logarithmic mean Divisia index) and Granger causality is adopted to decompose the influential factors of energy consumption and explores their potential relationships. The hybrid approach not only allows us to verify the contributions of energy consumption changes in the past (1990–2019), but also to identify the relationships between energy consumption and the potential factors. It is found that per urban population GDP (Gross Domestic Product) (accounting for 228.16 % contribution degree), infrastructure investment (accounting for 227.18 % contribution degree) and urbanization rate (accounting for 21.61 % contribution degree) are the top three driving forces of energy consumption. The Granger causality test shows that energy consumption has bilateral causality relationship with per urban population GDP, infrastructure investment and urbanization rate, but it has single Granger causality relationships with infrastructure investment population support coefficient and energy intensity in different lag lengths. Interestingly, our results indicate that the energy consumption, per urban population GDP, infrastructure investment and urbanization rate changes are closely related to urban policies or main events. Therefore, policy makers should not only make appropriate policies in infrastructure investment but also pay attention to the balance between energy consumption social-economic effects. • Decomposition of energy consumption in Shanghai by LMDI. • Exploring the potential relationship of factors by Granger causality test. • Temporal evolution of energy consumption in Shanghai was analyzed. • Five aspects related to energy consumption were investigated. [ABSTRACT FROM AUTHOR]

The type VI secretion system (T6SS) has been regarded as a late-model virulence factor widely distributed in Acinetobacter baumannii (A. baumannii). This study aimed to elucidate the clinical manifestations, the genetic background and microbiological characteristics of A. baumannii isolates causing bloodstream infection (BSI), and assessed the impact of T6SS carrying state on the clinical course. In this study, Clinical samples of A. baumannii causing BSI were collected from a teaching hospital in China from 2016 to 2020 and a retrospective cohort was conducted. Experimental strains were categorized into T6SS positive and negative groups through PCR targeting on hcp gene. The antimicrobials sensitivity test, virulence genes, biofilm formation ability, serum resistance of A. baumannii strains and Galleria mellonella infection model were investigated. Independent risk factors for T6SS+ A. baumannii BSI and Kaplan-Meier curve through follow-up survey were analyzed. A total of 182 A. baumannii strains were isolated from patients with BSI during 5 years and the medical records of all patients were retrospectively reviewed. The proportion of T6SS+ isolates was 62.64% (114/182), which exhibited significantly higher resistance rates of commonly used antibacterial drugs compared to T6SS- group. We found that T6SS+ A. baumannii strains had significantly weaker biofilm formation ability compared to T6SS- A. baumannii. Despite no difference in the positivity rate of tested virulence genes in two groups, T6SS+ strains exhibited higher resistance to the serum and increased virulence in vivo compared to T6SS- strains, indicating that T6SS is likely to enhance the survival and invasive capabilities of A. baumannii in vivo. Indwelling catheter, respiratory diseases, ICU history, white blood cell count and percentage of neutrophils increasing were independent risk factors for T6SS+ A. baumannii BSI. At last, the Kaplan-Meier curve confirmed a higher mortality rate associated with T6SS+ A. baumannii BSI, suggesting that the presence of T6SS may serve as a prognostic factor for mortality. In conclusion, our study revealed that T6SS+ A. baumannii exhibited distinct clinical features, characterized by high antimicrobial resistance and enhanced virulence, providing valuable insights for clinical treatment considerations. • T6SS+ Acinetobacter baumannii exhibits distinctive clinical traits and heightened virulence. • The T6SS+ A. baumannii strain demonstrates notably greater resistance compared to the T6SS- strain. • The T6SS+ strain exhibited a greater mortality rate in animal models, in line with the findings from follow-up surveys. [ABSTRACT FROM AUTHOR]

• Thirty-two chlorhexidine-tolerant isolates were detected from a total of 294 P. aeruginosa isolates collected from one of the largest comprehensive hospitals in China, accounting for a high rate of 10.9%. • Clinical data showed that reduced susceptibility to chlorhexidine was related to following factors: hospital length of stay, intensive care unit (ICU) admission, length of stay in ICU, invasive procedure, duration of mechanical ventilation, chlorhexidine usage, and occurrence of nosocomial pneumonia. • The hyperexpression of Mex-Opr efflux pump system was the main mechanism that lead to chlorhexidine tolerance. • Chlorhexidine usage or long-term exposure of P. aeruginosa to chlorhexidine could lead to the MDR or cross-resistance phenotypes of antimicrobial drugs. • Our study comprehensively investigates the development and molecular mechanisms of chlorhexidine-tolerant P. aeruginosa , which revealing that we should be aware of surveilling the chlorhexidine tolerance among P. aeruginosa and avoiding the continuous or unreasonable application of chlorhexidine in the hospital settings. Chlorhexidine is used widely to prevent the spread of bacteria in the hospital environment. However, bacteria are increasingly becoming tolerant to chlorhexidine. Here we investigated clinical characteristics, tolerance mechanisms, and molecular epidemiology of chlorhexidine-tolerant Pseudomonas aeruginosa. According to the proposed epidemiological cut-off value to determine chlorhexidine tolerance (50 µg/mL) in P. aeruginosa , 32 chlorhexidine-tolerant isolates were detected from 294 P. aeruginosa isolates, which accounted for 10.9%. Our results indicated MICs of chlorhexidine-tolerant strains were 64 µg/mL. Patient's data showed chlorhexidine tolerance was associated with following factors: hospital length of stay, ICU admission, length of stay in ICU, invasive procedure, duration of mechanical ventilation, chlorhexidine usage, and occurrence of nosocomial pneumonia. Tolerance mechanisms were analyzed by efflux pump inhibition test, qRT-PCR, and serial passage experiment. Increased expression of efflux pump genes mexA, mexC, mexE and mexX , and decreased expression of oprD were observed in chlorhexidine-tolerant and chlorhexidine-induced strains, which suggested that hyperexpression of Mex-Opr efflux pump was the main mechanism. Moreover, serial passage experiment found chlorhexidine-induced strains showed decreased susceptibility to tested antibiotics, which illustrated that long-term exposure of P. aeruginosa to chlorhexidine could result in multidrug-resistant (MDR) or cross-resistance phenotypes. MLST and PFGE analysis demonstrated the homology of 32 chlorhexidine-tolerant strains was low and no obvious clonal transmission was observed. We comprehensively investigated the development and molecular mechanisms of chlorhexidine-tolerant P. aeruginosa , which revealed that the control and surveillance of chlorhexidine tolerance should be more strict. Moreover, it seems to make sense to avoid the continuous or unreasonable application of chlorhexidine in hospital settings. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and mechanisms of ceftazidime/avibactam heteroresistance in KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, as well as the role of heteroresistance in the transition of ceftazidime/avibactam susceptibility to resistance., Methods: Clinical KPC-KP isolates were obtained from a tertiary hospital in China from 2016 to 2017 and 2019 to 2020. Antimicrobial susceptibility was determined by the broth microdilution method. Population analysis profiles were used to assess ceftazidime/avibactam heteroresistance. WGS and molecular cloning were conducted to reveal heteroresistance mechanisms and molecular characteristics., Results: The findings indicated that the transition of ceftazidime/avibactam susceptibility to resistance during the treatment of KPC-KP infection is primarily attributed to the heteroresistance exhibited by KPC-KP isolates towards ceftazidime/avibactam. Among 355 ceftazidime/avibactam-susceptible KPC-KP isolates (indicating a resistance rate of 0%), 41 (11.55%) exhibited ceftazidime/avibactam heteroresistance, with the primary mechanism being the presence of KPC mutant subpopulations. These KPC variants, arising from point mutations, deletions and insertions, significantly increased ceftazidime/avibactam resistance while alongside enhanced carbapenem susceptibility. Notably, 11 new KPC variants were identified. Furthermore, four heteroresistant isolates were caused by mixed infection involving subpopulations carrying NDM-1 or NDM-5. Phylogenetic analysis indicated that the clonal spread of ST11-KL64 KPC-KP may be correlated with the prevalence of heteroresistance., Conclusions: Ceftazidime/avibactam heteroresistance, primarily driven by pre-existing KPC variants, underscores the importance of considering heteroresistance in ceftazidime/avibactam therapeutics. Awareness of these dynamics is crucial for the effective and sustainable clinical application of ceftazidime/avibactam., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The widespread application of triclosan contributes to its residual deposition in urine, which provides an environment of long-term exposure to triclosan for the intestinal Escherichia coli. We determined the triclosan and antibiotic resistance characteristics of E. coli strains isolated from urine samples and further investigated the resistance mechanism and molecular epidemic characteristics of triclosan-resistant E. coli isolates., Methods: A total of 200 non-repetitive E. coli strains were isolated from urine samples and then identified. The minimum inhibitory concentrations (MICs) of triclosan and antibiotics, fabI mutation, efflux pump activity, the expression of 14 efflux pump encoding genes, and epidemiological characteristics were determined by the agar dilution method, polymerase chain reaction (PCR), carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibition test, quantitative real-time polymerase chain reaction (RT-qPCR), multilocus sequence typing (MLST), and pulse-field gel electrophoresis (PFGE) for all triclosan-resistant isolates. Furthermore, we also investigated the effect of triclosan exposure in vitro on antibiotic susceptibility and the efflux pump encoding gene expressions of triclosan-susceptible strains via serial passage experiments., Results: Of the 200 E. coli isolates, 2.5% (n = 5) were found to be resistant to triclosan, and multidrug resistance (MDR) and cross-resistance phenotypes were noted for these triclosan-resistant strains. The triclosan-sensitive strains also exhibited MDR phenotypes, probably because of the high resistance rate to AMP, CIP, LVX, and GEN. Gly79Ala and Ala69Thr amino acid changes were observed in the triclosan-resistant strains, but these changes may not mediate resistance of E. coli to triclosan, because mutations of these two amino acids has also been detected in triclosan-susceptible strains. Moreover, except for DC8603, all other strains enhanced the efflux pumps activity. As compared with ATCC 25922, except for fabI, increased expressions were noted for all efflux pump encoding genes such as ydcV, ydcU, ydcS, ydcT, cysP, yihV, acrB, acrD, and mdfA among the studied strains with varying PFGE patterns and STs types. Unexpectedly, 5 susceptible E. coli isolates showed rapidly increasing triclosan resistance after exposure to triclosan in vitro for only 12 days, while MDR or cross-resistance phenotypes and the overexpression of efflux pump genes were recorded among these triclosan-induced resistant isolates., Conclusions: This is the first study to report that short-term triclosan exposure in vitro increases triclosan resistance in susceptible E. coli isolates. After acquiring resistance, these strains may present MDR or cross-resistance phenotypes. Moreover, triclosan resistance mainly involves the overexpression of fabI and efflux pumps in E. coli isolates.