Background: Since May 2022, cases of monkeypox, a zoonotic disease caused by the monkeypox virus (MPXV), have been increasingly reported worldwide. There are, however, no proven therapies or vaccines available for monkeypox. In this study, several multi-epitope vaccines were designed against the MPXV using immunoinformatics approaches.Methods: Three target proteins, A35R and B6R, enveloped virion (EV) form-derived antigens, and H3L, expressed on the mature virion (MV) form, were selected for epitope identification. The shortlisted epitopes were fused with appropriate adjuvants and linkers to vaccine candidates. The biophysical andbiochemical features of vaccine candidates were evaluated. The Molecular docking and molecular dynamics(MD) simulation were run to understand the binding mode and binding stability between the vaccines and Toll-like receptors (TLRs) and major histocompatibility complexes (MHCs). The immunogenicity of the designed vaccines was evaluated via immune simulation.Results: Five vaccine constructs (MPXV-1-5) were formed. After the evaluation of various immunological and physicochemical parameters, MPXV-2 and MPXV-5 were selected for further analysis. The results of molecular docking showed that the MPXV-2 and MPXV-5 had a stronger affinity to TLRs (TLR2 and TLR4) and MHC (HLA-A*02:01 and HLA-DRB1*02:01) molecules, and the analyses of molecular dynamics (MD) simulation have further confirmed the strong binding stability of MPXV-2 and MPXV-5 with TLRs and MHC molecules. The results of the immune simulation indicated that both MPXV-2 and MPXV-5 could effectively induce robust protective immune responses in the human body.Conclusion: The MPXV-2 and MPXV-5 have good efficacy against the MPXV in theory, but further studies are required to validate their safety and efficacy.

Carbapenem-resistant K. pneumoniae (CR-KP) posts significant public health challenge worldwide. The aim of this study is to assess clinical characteristics and molecular epidemiology of CR-KP infections with Multilocus sequence typing (MLST) and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) in Central China. A total of 71 CR-KP isolates were recovered in a teaching hospital from October 2014 to December 2015. Among all CR-KP isolates, 73.2% (52) produced K. pneumoniae carbapenemases-2 (KPC-2). Eighteen ST types were identified by MLST, among these ST types, forty-seven isolates belonged to ST11 type, which was the predominant outbreak strain in China, and most ST11 isolates produced KPC-2. Eleven mass spectrometry (MS) types were identified by MALDI-TOF MS analysis, 53.5% isolates were MS4 and MS6, which matched with ST11 in MLST analysis. CR-KP infection was associated with increased medical cost and longer hospitalization. Therefore, we found that KPC-2-producing ST11 (MS4 and MS6) CR-KP isolates were the predominant clone identified by MLST and MALDI-TOF, and CR-KP infection was associated with increased hospital costs and longer hospitalization.

The gut microbiota composition of intensive care unit (ICU) patients suffering from Clostridium difficile-positive diarrhea (CDpD) is poorly understood. This prospective study aims to use 16S rDNA (and metagenome) sequencing to compare the microbiota composition of 58 (and 5) ICU patients with CDpD (CDpD group), 33 (and 4) ICU patients with C. difficile-negative diarrhea (CDnD group), and 21 (and 5) healthy control subjects (control group), as well as CDpD patients in the A⁺B⁺ (N = 34; A/B: C. difficile TcdA/B), A⁻B⁺ (N = 7), and A⁻B⁻ (N = 17) subgroups. For 16S rDNA data, OTU clustering (tool: UPARSE), taxonomic assignment (tool: RDP classifier), α-diversity, and β-diversity analyses (tool: QIIME) were conducted. For metagenome data, metagenome assembly (tool: SOAPdenovo), gene calling (tools: MetaGeneMark, CD-HIT, and SoapAligner), unigene alignment (tool: DIAMOND), taxon difference analysis (tool: Metastats), and gene annotation (tool: DIAMOND) were performed. The microbial diversity of the CDpD group was lower than that of the CDnD and control groups. The abundances of 10 taxa (e.g., Deferribacteres, Cryptomycota, Acetothermia) were significantly higher in the CDpD group than in the CDnD group. The abundances of Saccharomycetes and Clostridia were significantly lower in CDpD in comparison with control. Some taxa were significantly different between the A⁺B⁺ and A⁻B⁻ subgroups. CDpD might relate to a decrease in beneficial taxa (i.e., Saccharomycetes and Clostridia) and an increase in harmful taxa (e.g., Deferribacteres, Cryptomycota, Acetothermia) in gut microbiota of ICU patients. C. difficile toxin type might be slightly associated with gut microbiota composition.

The emergence and spread of Carbapenem-resistant Escherichia coli (CREC) is becoming a serious problem in Chinese hospitals, however, the data on this is scarce. Therefore, we investigate the risk factors for healthcare-associated CREC infection and study the incidence, antibiotic resistance and medical costs of CREC infections in our hospital. We conducted a retrospective, matched case–control–control, parallel study in a tertiary teaching hospital. Patients admitted between January 2012 and December 2015 were included in this study. For patients with healthcare-associated CREC infection, two matched subject groups were created; one group with healthcare-associated CSEC infection and the other group without infection. Multivariate conditional logistic regression analysis demonstrated that prior hospital stay (<6 months) (OR:3.96; 95%CI:1.26–12.42), tracheostomy (OR:2.24; 95%CI: 1.14–4.38), central venous catheter insertion (OR: 8.15; 95%CI: 2.31–28.72), carbapenem exposure (OR: 12.02; 95%CI: 1.52–95.4), urinary system disease (OR: 16.69; 95%CI: 3.01–89.76), low hemoglobin (OR: 2.83; 95%CI: 1.46–5.50), and high blood glucose are associated (OR: 7.01; 95%CI: 1.89–26.02) with CREC infection. Total costs (p = 0.00), medical examination costs (p = 0.00), medical test costs (p = 0.00), total drug costs (p = 0.00) and ant-infective drug costs (p = 0.00) for the CREC group were significantly higher than those for the no infection group. Medical examination costs (p = 0.03), total drug costs (p = 0.03), and anti-infective drug costs (p = 0.01) for the CREC group were significantly higher than for the CSEC group. Mortality in CREC group was significantly higher than the CSEC group (p = 0.01) and no infection group (p = 0.01). Many factors were discovered for acquisition of healthcare-associated CREC infection. CREC isolates were resistant to most antibiotics, and had some association with high financial burden and increased mortality.

Purpose Hospital-acquired pneumonia (HAP) remains one of the major hospital-acquired infections in China. Antibiotic treatment of HAP may lead to subsequent Clostridium difficile infection (CDI). Baseline data on the occurrence of CDI among HAP patients in China are currently unavailable. This study examines the risk and disease burden of CDI among HAP hospitalized patients (HAP-CDI). Methods We conducted a prospective study among ICU patients with HAP and hospital-onset diarrhea from January 2014 to December 2014 in a teaching hospital in China. All stool specimens were cultured for C. difficile which were typed by MLST. We used univariate and multivariable regression analyses to identify risk factors of HAP-CDI. Findings In total, 369 patients who met the inclusion criteria were enrolled. Thirty-two patients tested C. difficile positive. Among the isolated C. difficile strains, 90.63% (29/32) isolates were toxinogenic. Various MLST types were identified. The incidence of HAP-CDI was 11.67/10,000 patient days (95% CI, 7.97–16.55). Nineteen patients died from complications. The attributable mortality rate was 5.15% (19/369). The mortality rate of HAP-CDI group was 13.79% which was higher than HAP-non-CDI group. Univariate analyses demonstrated that old age, receiving antibiotics (OR = 8.70) and glucocorticoids (OR = 7.71) 1 month prior to hospitalization, respiratory failure (OR = 3.28) and receiving antimicrobials during hospitalization (OR = 1.15) were the risk factors associated with CDI. Multivariate conditional logistic regression analysis demonstrated the similar results. Conclusion CDI was common among patients discharged from hospital for HAP at a university hospital. Prevention of the spreading of C. difficile among hospitalized patients is urgently needed.