OBJECTIVE:Investigating the incidence of the cefazolin inoculum effect (CzIE) in methicillin-susceptible Staphylococcus aureus and its correlation with the blaZ gene. METHODS:Genotyping and blaZ gene detection using Sanger sequencing were conducted on 113 methicillin-susceptible S. aureus (MSSA) isolates from bloodstream infections at a tertiary hospital in Hangzhou, Zhejiang Province, collected from January 2021 to October 2024. Cefazolin susceptibility was determined using the broth microdilution method under standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum conditions. Statistical analysis was performed using SPSS Statistics 29.0. RESULTS:Among the 113 MSSA strains, 94 carried the blaZ gene, with the highest proportion being type C (57/94, 60.6%), followed by type A (21/94, 22.4%), type B (16/94, 17.0%), and no type D was detected. The overall CzIE prevalence was 12.4% (14/113). blaZ type A isolates exhibited a significantly higher CzIE rate (42.9%, 9/21) compared to type B (0%, 0/16) and type C (9.8%, 5/57) (P < 0.0167). CONCLUSIONS:The incidence of CzIE in MSSA was 12.4%. While blaZ type C was the most common, blaZ type A exhibited the most significant correlation with CzIE. Clinicians must remain alert for blaZ type A strains, as their significant inoculum effect may elevate the probability of cefazolin treatment failure in severe MSSA infections.

OBJECTIVES:Resistance to polymyxin B (PMB) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become a global issue. A promising approach to rescue PMB treatment failures is to repurpose non-antibiotics as adjuvants to enhance the efficacy of antibiotics against CRPA. METHODS:The in vitro effects of the PMB/DDC combination were assessed by microbroth dilution method, checkerboard microbroth dilution method, time-kill assay, biofilm formation inhibition assay, live/dead bacterial staining, and scanning electron microscopy. The in vivo efficacy of the PMB/DDC combination was evaluated in a PMB-resistant P. aeruginosa infection model. Comprehensive multi-omics analysis was performed to investigate the mechanism of the PMB/DDC combination. RESULTS:We identified that the combination of PMB and diethyldithiocarbamate (DDC) had a high synergistic effect against PMB-resistant Pseudomonas aeruginosa (P. aeruginosa) strains in vitro and significantly hindered the biofilm formation. The PMB/DDC combination was effective in treating PMB-resistant P. aeruginosa infection model in vivo, as evidenced by higher survival rates in five days and lower bacterial loads in lung tissue and liver. Comprehensive multi-omics analysis revealed that the resistance of P. aeruginosa P2550 to PMB was determined by chromosomally encoded rather than plasmid-mediated mobilized colistin resistance (MCR) clusters. The combination down-regulated the expression of the operons arnBCADTEF at 2 h, which regulate LPS modification, and the abundance of metabolites of amino sugars and nucleotide sugars related to Lipid A biosynthesis and Lipid A modification were significantly perturbed. The Gac/Rsm pathway, quorum sensing (QS) system, cAMP/Vfr signalling, and c-di-GMP signalling, which are pathways associated with biofilm formation, were significantly inhibited within the first 4 h. In addition, the PMB/DDC combination significantly disturbed metabolic pathways, including arginine biosynthesis, the tricarboxylic acid cycle (TCA), and nucleotide metabolism. Notably, PMB alone, DDC alone, and the combination disrupted membrane-associated glycerophospholipid metabolism. CONCLUSIONS:The study highlights the potential of the PMB/DDC combination for treating PMB-resistant P. aeruginosa infections and elucidates the synergistic bactericidal mechanism of the combination through multi-omics methods.

Background: With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN. Methods: We conducted a comprehensive bidirectional Mendelian randomization (MR) study. We selected 211 bacterial taxa using Genome-wide association study (GWAS) data provided by the MiBioGen consortium, while GWAS data relevant to MN were obtained from ebi-a-GCST010005. The inverse-variance weighted (IVW) method was the primary technique used to delineate the causal relationship between exposures and outcomes. To confirm the robustness of our results, we used additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses included tests for pleiotropy, heterogeneity, and leave-one-out sensitivity to ensure the integrity of our conclusions. Finally, reverse MR analyses were conducted to assess the likelihood of reverse causality. Results: Using various analytical methods, including the IVW approach, MR-Egger, weighted median, simple mode, and weighted mode, our study identified six microbial taxa with a statistically significant causal link to MN, as indicated by p-values less than 0.05. The implicated taxa are Butyrivibrio (OR= 1.25, 95 % CI: 1.001-1.565, P = 0.048), Butyricicoccus (OR = 2.15, 95 % CI: 1.005-4.621, P = 0.048), Catenibacterium (OR = 1.49, 95 % CI: 1.043-2.134, P = 0.028), Ruminiclostridium5 (OR = 1.78, 95 % CI: 1.140-2.763, P = 0.03), RuminococcaceaeUCG003 (OR = 1.78, 95 % CI: 1.140-2.763, P = 0.011) and Bacillales (OR = 1.52, 95 % CI: 1.135-2.025, P = 0.005). Each of these taxa has been established as a risk factor for MN. Notably, Ruminococcaceae UCG-003 and Bacillales were identified as having a bidirectional causal relationship with the disease. Conclusion: Our MR study has revealed a causal link between six microbial taxa and MN, highlighting their potential involvement in the disease's development. These findings represent an initial step into this complex field and underscore the need for more in-depth research.

CRKP infections are a significant public health threat due to their high mortality and limited treatment options. This study aimed to investigate CRKP colonization and clonal dissemination mechanism in an ICU. From August 2019 to December 2019, 8668 samples were collected from patients and the ICU environment for CRKP screening. Positive samples underwent antimicrobial susceptibility testing, whole-genome sequencing, and molecular epidemiological analysis. Disinfectant sensitivity and ultraviolet (UV) resistance experiments were conducted to evaluate clonal persistence. The overall CRKP positive rate was 4.85% (420/8668), with higher rates in patients (14.77%, 247/1672) compared to environmental surfaces (2.47%, 173/6996). Intestinal and ventilator-related surfaces were identified as high-risk colonization sites. Molecular analysis revealed six sequence types, with ST11-KL64 (44.05%, 185/420) and ST15-KL112 (24.05%, 101/420) as dominant clones, both exhibiting elevated virulence. Notably, the emerging ST15-KL112 clone demonstrated enhanced resistance to disinfectants including chlorhexidine (MIC 8 mg/L) and benzalkonium chloride (32 mg/L). While most isolates produced KPC-2 (72.86%), OXA-232 prevalence (25.23%) exceeded prior reports. Crucially, ST11 strains survived standard UV disinfection (60-second exposure) at rates 1.3- to 5-fold higher than other clones (p < 0.01). Our findings highlight the critical role of disinfectant resistance in sustaining CRKP transmission. To mitigate outbreaks, we advocate for disinfectant rotation protocols targeting disinfectant-resistant clones and prolonged UV exposure times in ICUs. The persistence of resistant CRKP clones in the ICU environment, particularly their high tolerance to disinfectants, highlights the urgent need for enhanced infection control strategies, including tailored disinfection protocols and surveillance programs.

BACKGROUND:Prostate adenocarcinoma (PRAD) is the most prevalent malignancy in men and frequently evades early detection. However, the role of genes containing adenylate uridylate- (AU-) rich elements (AREGs) in PRAD remains largely uncharacterized. METHODS:Publicly available PRAD datasets were analyzed through weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules. Unsupervised clustering defined AREG-associated molecular subtypes. Prognostic genes were selected via univariate/multivariate Cox proportional hazards regression (Cox) regression and least absolute shrinkage and selection operator (LASSO) regularization. Tumor immune infiltration was profiled using CIBERSORT and other bioinformatic tools, with functional enrichment revealing associated mechanisms. Single-cell transcriptomics (TISCH2) and drug sensitivity predictions (CellMiner) were integrated. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) validated hub gene expression in PRAD. RESULTS:We identified three AU-rich element-related prognostic genes: ACSM3, ACTG2, and DES. The low-risk group exhibited enhanced immune pathway activity and elevated tumor-infiltrating immune cell levels compared to high-risk patients. Functional analyses linked high-risk scores to pathways such as glycosylation and proteasome regulation. Single-cell transcriptomics revealed widespread expression of ACSM3, while ACTG2 and DES were fibroblast-enriched. Drug sensitivity predictions suggested Docetaxel as a potential therapeutic agent for high-risk PRAD patients. CONCLUSIONS:In this study, we propose that an AREG-based signature comprising ACSM3, ACTG2, and DES effectively predicts prognosis and reflects immune microenvironment characteristics in PRAD. Through systematic analysis, we established a prognostic model utilizing these three AREGs, which demonstrates strong potential as a clinical predictor for PRAD patient outcomes.

Therapeutic vaccinations that enhance human immunodeficiency virus (HIV)-specific immunity hold promise for reducing reliance on antiretroviral therapy (ART). We previously developed an adenovirus vector-infected peripheral blood mononuclear cell (AVIP) as a prophylactic strategy that enhanced cellular immunity in macaques and significantly reduced set-point and peak simian immunodeficiency virus (SIV) loads following SIV challenge. However, its therapeutic efficacy remains to be fully explored. In this study, we improved AVIP by enhancing adenovirus entry into peripheral blood mononuclear cells (PBMCs) through in vitro co-incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF). We constructed adenoviruses carrying SIV group-specific antigen (Gag), envelope (Env), and polymerase (Pol) and evaluated the therapeutic potential of autologous AVIP infusion in acute SIV-infected macaques. Compared with ART alone, AVIP in combination with ART elicited robust cellular immunity against SIV, effectively controlled SIV replication during ART, and delayed viral rebound and acquired immunodeficiency syndrome (AIDS) progression after ART discontinuation. Notably, 80% of macaques in AVIP+ART group maintain plasma virus control for at least 100 days after ART interruption. This sustained viral control is associated with vaccine-induced Pol-specific immune responses and reduced CD38 expression on CD8+ T cells. These findings support further investigation of AVIP as a therapeutic strategy against acute HIV infection.

Background Mycoplasma hominis, a commensal organism, is potentially pathogenic; its role in postoperative infections might be underestimated in cardiac surgery. Results We reported two cases of postoperative M. hominis mediastinitis in immunocompetent patients with a DeBakey grade I aortic dissecting aneurysm and reviewed 10 other cases previously described. Among the 10 reviewed cases and our two cases, 11 patients were men (median age, 59 years; median onset of clinical symptoms time, 14.5 d after surgery; and mean peak of temperature, 38.5±0.8°C). In our reports, two patients underwent sternotomy site reopening and debridement before diagnosis was confirmed. Diagnosis was confirmed by prolonged culture and by performing metagenomic next-generation sequencing directly using the clinical samples. M. hominis was difficult to cover with initial empirical antibiotic therapy; the patient in this study showed complete improvement with long-term antimicrobial therapy. The targeted treatment duration for surviving patients among the reviewed cases ranged from three weeks to 16 months. Conclusions The diagnosis of extragenital M. hominis infections is difficult. Therefore, the role of M. hominis as a cause of postoperative infections during cardiac surgery should be considered. Diagnosis requires molecular techniques to complement culture.

The aim of this study was to explore the mechanisms and molecular epidemiology of carbapenem resistance in the carbapenem-resistant Enterobacter cloacae complex (CRECC) over a decade in a tertiary hospital in Zhejiang, China. From January 2011 to December 2021, we collected a total of 931 Enterobacter cloacae complex (ECC) isolates from a tertiary hospital in Zhejiang, China. Antimicrobial susceptibility tests were performed. Whole-genome sequencing was used to analyze the molecular characteristics of the CRECC isolates. For carbapenem-resistant strains, efflux inhibitor assay and quantitative real-time PCR (qRT-PCR) were performed to evaluate the function of efflux pumps. A total of 82 CRECC isolates were detected, and the rate of resistance for carbapenems was 8.8%, increasing from 5.5% in 2011 to 18.3% in 2019, with an overall increasing trend, with Enterobacter hormaechei subsp. hoffmannii being the predominant species. Among the CRECC, 24 (24/931) isolates were found to produce carbapenemases, including NDM-1, NDM-5, IMP-4, and KPC-2. Among all carbapenemases, NDM-1 was the most prevalent, accounting for 62.5% (15/24) of carbapenemases, followed by NDM-5 (5/24). Genes encoding extended-spectrum beta-lactamases (47/82) and AmpC (76/82) were also identified, with bla(SHV-12) and bla(ACT) being the predominant ones, respectively. Multilocus sequence typing revealed 28 different sequence types, among which ST78 was the predominant, followed by ST93 and ST177. IncFIB was the most common type of plasmid replicon. Efflux inhibitor assay and qRT-PCR indicated that the overexpression of efflux pumps was involved in carbapenem resistance mechanisms. Additionally, disrupted outer membrane proteins also contribute to carbapenem resistance. The detection rate of CRECC was rising in the tertiary hospital. Bla(NDM-1) and bla(NDM-5) were the main carbapenem resistance genes. Our study revealed the presence of carbapenem-resistant ECC strains, emphasizing the need for effective infection prevention approaches to reduce the prevalence of CRECC. IMPORTANCE The emergence and spread of the carbapenem-resistant Enterobacter cloacae complex (CRECC) have become a significant public health problem. CRECC strains frequently harbor multiple drug resistance genes and can be epidemic within healthcare facilities. The study explored the characteristics and prevalence of CRECC strains in the same hospital over a decade, which provides a theoretical basis for epidemiologic surveillance and clinical treatment.

Abstract Background: Carbapenem-resistant Pseudomonas aeruginosa sequence type 463 (ST463-CRPA) with high-virulence and high-resistance has emerged and spread rapidly in East China. The aim of the study was to investigate the distribution and characteristics of the emerging high-risk ST463-CRPA in intensive care unit (ICU) in East China. Methods: The 11-month-span study investigated the epidemiological characteristics, genetic composition, and transmission pattern of CRPA isolated from patients and environments of 5 different ICUs in a large teaching hospital in East China. Whole-genome sequencing, antibiotic susceptibility testing and biofilm-forming ability testing were performed in all CRPA isolates. The molecular epidemiological characteristics and the phylogenetic relationships of isolates from different sources were assessed using multi-locus sequence typing (MLST) and core genome multi-locus sequence typing (cgMLST). Bacterial virulence was assessed using a Galleria mellonella infection model. Results: According to the MLST scheme, all of CRPA isolates fell into 25 defined STs, of which 24.07% (13/54) CRPA belonged to ST463 as the dominant ST in ICUs. All 13 ST463-CRPA strains, including 4 from patients and 9 from environments mainly in washbasins, carried blaKPC-2 gene with exoU+/exoS+ virulence genotype showing difficult-to-treat resistance (DTR) phenotype. ST463-CRPA had higher biofilm-forming ability and mortality of infected larvae than non-ST463-CRPA (P<0.05). No differences on virulence were detected between the CRPA from environments and infected patients. CgMLST results revealed that several ST463-CRPA strains isolated from different ICUs had genetic relationship. Notably, 3 ST463 strains harboring both blaAFM-1 and blaKPC-2 genes with 41-59 SNPs difference were isolated from different ICUs. Conclusions: In combination with epidemiological data linked in time and space, the cgMLST results elucidated polyclonal dissemination of CRPA and a distribution of ST463-CRPA among ICUs in a large hospital of East China. As the dominant ST found in ICU especially in environments, KPC-ST463-CRPA might be considered a strain with potential to cause a future outbreak, which could acquire the blaAFM gene additionally, leading to the resistance to last-resort antibiotics. Hence, it’s worth our vigilance about the growing prevalence of ST463-CRPA in ICU of East China. Meanwhile, it’s important to strengthen the management of ICU environment, especially the water reservoirs.

Iron metabolism is considered to play the principal role in sepsis, but the key iron metabolism-related genetic signatures are unclear. In this study, we analyzed and identified the genetic signatures related to the iron-metabolism in sepsis by using a bioinformatics analysis of four transcriptomic datasets from the GEO database. A total of 21 differentially expressed iron metabolism-related signatures were identified including 9 transporters, 8 enzymes, and 4 regulatory factors. Among them, lipocalin 2 was found to have the highest diagnostic value as its expression showed significant differences in all the comparisons including sepsis vs healthy controls, sepsis vs non-sepsis diseases, and mild forms vs severe forms of sepsis. Besides, the cytochrome P450 gene CYP1B1 also showed diagnostic values for sepsis from the non-sepsis diseases. The CYP4V2, LTF, and GCLM showed diagnostic values for distinguishing the severe forms from mild forms of sepsis. Our analysis identified 21 sepsis-associated iron metabolism-related genetic signatures, which may represent diagnostic and therapeutic biomarkers of sepsis, and will improve our understanding of the molecular mechanism underlying the occurrence of sepsis.

A rare case of fungus Arthroderma multifidum infection occurred in a 63-year-old man. The patient had some risk factors, including occupational exposure, immunosuppressive state, and structural basis following pulmonary tuberculosis and pneumothorax surgery. The pathogen was repeatedly isolated from bronchoalveolar lavage fluid and identified by gene sequencing. It is the first report of human infection caused by A. multifidum. Whole genome sequencing and analysis of its genomic characterization are completed. The findings provide us with a key clinical insight that the combination of immune suppression and environmental exposure could create an ideal condition for zoonotic fungal infections.

Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (As2O3) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of As2O3 independent of ART in chronically SIV-infected macaques. We found that As2O3-only treatment significantly increased the CD4/CD8 ratio, improved SIV-specific T cell responses, and reactivated viral latency in chronically SIVmac239-infected macaques. RNA-sequencing analysis revealed that As2O3 treatment downregulated the expression levels of genes related to HIV entry and infection, while the expression levels of genes related to transcription initiation, cell apoptosis, and host restriction factors were significantly upregulated. Importantly, we found that As2O3 treatment specifically induced apoptosis of SIV-infected CD4(+) T cells. These findings revealed that As2O3 might not only impact viral latency, but also induce the apoptosis of HIV-infected cells and thus block the secondary infection of bystanders. Moreover, we investigated the therapeutic potential of this regimen in acutely SIVmac239-infected macaques and found that As2O3 + ART treatment effectively restored the CD4(+) T cell count, delayed disease progression, and improved survival in acutely SIV-infected macaques. In sum, this work provides new insights to develop As2O3 as a component of the "shock-and-kill" strategy toward HIV functional cure. IMPORTANCE Although antiretroviral therapy (ART) can effectively suppress the viral load of AIDS patients, it cannot functionally cure HIV infection due to the existence of HIV reservoir. Strategies toward HIV functional cure are still highly anticipated to ultimately end the pandemic of AIDS. Herein, we investigated the direct role of As2O3 independent of ART in chronically SIV-infected macaques and explored the underlying mechanisms of the potential of As2O3 in the treatment of HIV/SIV infection. Meanwhile, we investigated the therapeutic effects of ART+As2O3 in acutely SIVmac239-infected macaques. This study showed that As2O3 has the potential to be launched into the "shock-and-kill" strategy to suppress HIV/SIV reservoir due to its latency-reversing and apoptosis-inducing properties.

Background: Recently, emerging high-risk sequence type (ST) 463 carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become increasingly prevalent in China.Methods: Two ceftazidime/avibactam (CZA)-resistant P. aeruginosa strains, ZYPA54 and SYPA07, causing fatal infections, were isolated from two immunocompromised patients during CZA therapy. Whole-genome sequences were obtained, and minimum inhibitory concentrations (MICs) were determined. Conjugation experiments were conducted. Expression levels of mexA, mexX, oprD, and ampC were measured, and virulence was assessed.Findings: ZYPA54 and SYPA07 presented extensively drug-resistant (XDR) phenotypes, only susceptible to aminoglycosides and intermediate to colistin. Both strains belonged to ST463 and carried the blaKPC-2 variant blaKPC-33 that conferred CZA resistance. Mutations in blaKPC-2 did not restore susceptibility to carbapenems as OprD was deficient in the two strains. blaKPC-33 genes resided on untransferable plasmids and inhabited the conserved unit (ISKpn27 -blaKPC-33-ISKpn6) flanked by two copies of IS26, highlighting their potential for horizontal transmission. Both patients responded poorly to antibiotics and eventually died owing to septic shock and multi-organ failure within two weeks of ZYPA54 and SYPA07 culture results. Analysis of the type III secretion system genotype showed that both strains were positive for exoU, exoS, exoY, and exoT. ZYPA54 and SYPA07 exhibited potent cytotoxicity and killed 100% of the Galleria mellonella inoculated with 1 × 104 CFU of bacteria within 24 h, indicating their hypervirulence.Interpretation: These novel blaKPC-33-harboring ST463 P. aeruginosa strains are XDR and hypervirulent, imperiling human health. CZA is a promising candidate for clinical application but should be used with caution. Surveillance of the emerging high-risk ST463 clones is warranted.Funding Information: This study was supported by The National Natural Science Foundations of China (grant number NSFC81871689).Declaration of Interests: We declare no competing interests.Ethics Approval Statement: All clinical data were collected from the electronic medical record system. This study was conducted in the First Affiliated Hospital of Zhejiang University in China and approved by its ethical research committee (approval no. IIT20210120B). As this was a retrospective study of anonymous data, informed consents of two patients were waived off.

BACKGROUND:Trace metals/metalloids were important for the biological functions of both the eukaryotic host and the microorganism. Their concentrations and variations may associate with the critical illness in sepsis, which still needs to be investigated. METHODS:We performed a prospective cohort study on the patients with sepsis admitted to Tongji hospital (Wuhan, China) from Jul 01 to Dec 31, 2021. Sepsis was diagnosed in accordance with the third international consensus definitions for sepsis and septic shock (Sepsis-3). The concentrations of metals/metalloids including magnesium (Mg), calcium (Ca), chromium (Cr), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), mercury (Hg), thallium (Tl) and lead (Pb) in whole blood were analyzed by ICP-MS based methods. RESULTS:Compared to the healthy controls, patients with sepsis showed higher levels of Ca, Cr and Cu, and lower levels of Mg, Mn, Fe, Zn, As, Hg and Pb. Further analysis between the critical illness and noncritical illness, revealed the Mn, Fe were significantly lower in the critically-ill sepsis. The longitudinal profile of the two metals show the differences appeared to exist almost throughout the clinical course. By performing the binary regression logistic analysis, we determined the Fe, Mn as independently risk factors for critical illness in sepsis, with effect sizes (β) of 17.14 (95%CI: 1.79-163.81) and 10.83 (1.96-59.83), respectively, which collectively discriminated 83.3% of all cases between critical-illness and non-critically illness. CONCLUSIONS:The variations of whole blood metals/metalloids were associated with the critically-ill sepsis.

当前,细菌耐药已成为全球公共健康领域的重大挑战,其中尤以碳青霉烯类耐药肠杆菌目细菌(carbapenem-resistant Enterobacterales, CRE)引起的感染形势最为严峻.碳青霉烯类抗生素包括亚胺培南、美罗培南和厄他培南等,是治疗多重耐药革兰阴性杆菌所致感染最有效的抗菌药物之一.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Chronic hepatitis B (CHB) and acquired immunodeficiency syndrome (AIDS) are global public health problems that pose a significant health burden. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is common, as these viruses have similar transmission routes, such as blood transmission, sexual transmission and mother-to-child transmission. Coinfection frequently leads to accelerated disease progression. For individuals coinfected with HIV/HBV, combination antiretroviral therapy containing dual anti-HBV drugs is recommended. Certain studies have also indicated the benefits of antiretroviral drugs with anti-HBV activity in patients with coinfection. A total of four Food and Drug Administration-approved HIV drugs also have anti-HBV activity; namely, emtricitabine, lamivudine, tenofovir disoproxil fumarate and tenofovir alafenamide, which are all nucleoside reverse transcriptase inhibitors. However, various issues, including drug resistance and side effects, limit their application. Therefore, it is necessary to develop more drugs with dual activity against HBV and HIV. The present review outlines the mechanisms, safety and efficacy of certain drugs that have been investigated for this purpose.

We aimed to compare efficacy of different patterns of antibiotics and explore the risk factors related to mortality in patients with bloodstream infections (BSIs) due to carbapenem-resistant Klebsiella pneumoniae (CRKP). This study retrospectively included 89 patients with BSIs due to CRKP with complete data during the year of 2018 in the First Affiliated Hospital of Zhejiang University School of Medicine. Overall, the 28-day mortality was 47.2% (42/89). Multivariate analysis of Cox regression revealed that hematological malignancy (hazard ratio [HR] 5.698; 95% confidence interval [CI], 2.405-13.504; p < 0.001) and Pitt bacteremia score (HR per unit increase, 1.303; 95% CI, 1.109-1.532; p = 0.001) were identified as independent predictors for 28-day mortality. Among 70 patients with appropriate therapy, 35 received tigecycline (TGC)-based therapy, 20 received polymyxin B (PMB)-based therapy, 9 received ceftazidime/avibactam-based therapy, and 6 patients had other kinds of antibiotics, including ciprofloxacin, amikacin, and cotrimoxazole. By adjusting variables selected by crude analysis, it showed that receiving PMB-based therapy provided a survival benefit comparing with TGC-based therapy (HR, 0.068; 95% CI, 0.018-0.260; p < 0.001). Hematological malignancy and Pitt bacteremia score were independent risk factors of death in patients with BSIs due to CRKP and PMB-based therapy improved survival rate compared with TGC-based therapy.