| Background Vibrio cholerae mostly causes intestinal infections,leading to diarrhea.V.cholerae O1,which produces cholera toxin,has caused the sixth and seventh global cholera pandemics and becomes a serious public health threat.The non-toxigenic V.cholerae,which are mainly environmental colonizing bacteria,can cause diarrhea but are uncommon and rarely cause diarrheal outbreaks.The bacteria can cause bloodstream infections,which result in severe sepsis and septicemia.Among the pathogens in which bloodstream infections occur,V.cholerae,although relatively rare,has been reported.Currently,there are many case studies on bloodstream infection with V.cholerae,but systematic epidemiological and etiological characteristics studies are limited.Systematic analysis of the triple interval distributions,sources of infection,clinical presentations,primary diseases and risk factors of bloodstream infection with V.cholerae has not been carried out yet.There is also a lack of comprehensive analysis of serogroups,virulence genes,drug resistance and drug-resistant genes,phylogenetic structure of V.cholerae strains isolated from human bloodstream infectionObjectives To systematically collect case information and strains of V.cholerae bloodstream infection.To explore the epidemiological characteristics of cases of bloodstream infection with V.cholerae,such as triple interval distributions,sources of infection,clinical presentations,underlying diseases,outcomes and prognosis.To analyze the risk factors for the occurrence of bloodstream infection and death in infected cases.To analyze the virulence genes,drug resistance and drug-resistant genes,phylogenetic structure and other etiological characteristics of V.cholerae strains isolated from human bloodstream infection.To provide a basis of understanding for clinical assessment of the prognosis and treatment of bloodstream infections with V.cholerae,as well as in-depth analysis of the mechanism of V.cholerae invasive infection.Methods Cases of bloodstream infections with V.cholerae were collected by searching literature in Chinese and foreign language databases and relying on the National Pathogen Identification Network.A database was established,and then the triple interval distributions,sources of infection,clinical presentations,underlying diseases of cases of bloodstream infections with V.cholerae were described.Risk factors for death in infected cases were analyzed using a binary logistic regression approach.V.cholerae strains isolated from human bloodstream infection were collected for serogroup identification,antimicrobial susceptibility testing,whole genome sequencing and analysis.BLAST online comparison software was used for comparison and analysis with Resfinder,VFDB and other databases to clarify the drug-resistant genes and virulence genes carried by the strains.MEGA 5.1 software was used to construct a genetic phylogenetic tree based on core genome single nucleotide polymorphisms.Results A total of 299 clinical data of bloodstream infection with V.cholerae cases were collected.There were more males(77.5%),with a sex ratio of 3.5:1.The cases occurred mostly in summer and coastal areas.The clinical presentations were predominantly diarrhea and/or abdominal pain,nausea and/or vomiting,chills.51.7%of the cases had underlying cirrhosis.The prevalence of respiratory distress,infectious shock,bulla,metabolic acidosis was higher in fatal cases compared to survival cases(P<0.05).Serogroups of 300 target strains were obtained by serological identification,the National Pathogen Identification Network and literature search,most of which were non-O1/non-O139 groups.V.cholerae strains isolated from bloodstream infection had the highest rate of drug resistance to polymyxin E(87.0%),followed by streptomycin(29.6%)and nalidixic acid(20.4%).The sensitivity rates to amikacin,tigecycline,azithromycin,chloramphenicol and ceftazidime/avibactam were higher.Only one strain(1.9%,serogroup O139)carried ctxAB,which codes for cholera toxin,while 23 virulence-related genes could be found in other strains by genomic sequencing.The strains carried a wide variety of drug-resistant genes,involving eight classes of antibiotics.Genes catB9,qnrVC4,dfrA31,qnrVC5,sul2,floR,aph(3")-Ib,aph(6)-Id,blaCARB-7 were carried in more than 10%,and other drug-resistant genes were carried in less than 10%.V.cholerae strains isolated from bloodstream infection had multi-drug resistance,and 22 strains of multi-drug resistant strains existed in this study,with 19 drug-resistant profiles were screened.The resistance phenotypes and resistance genes of the strains to tetracyclines and sulfonamides were in good agreement(0.4<Kappa≤0.75).V.cholerae strains isolated from bloodstream infection were mostly of non-Ol/non-O139 serogroup,and their genomic structure was co-dispersed in multiple evolutionary branches with diarrhea patient isolates.A toxin-producing strain of the O139 group identified in this study was a multi-drug resistant strain,carrying multiple virulence-related genes and virulence islands,containing IncA/C resistance plasmids and multi-drug resistance islands,and its cgMLST type was a novel type highly similar to cgST-252.Conclusions The presence of underlying disease,especially cirrhosis,is a potential risk for V.cholerae invasive infection,which may also be associated with factors that contribute to V.cholerae proliferation,such as summer and eating seafood.The presence of respiratory distress,infectious shock,bulla and metabolic acidosis increase the risk of death in cases with V.cholerae invasive infection.V.cholerae isolated from bloodstream infection are almost non-toxigenic strains,with have distinctly different genomic evolutionary branches from the seventh pandemic strains.They are highly divergent from each other and do not aggregate into unique clonal groups.However,invasion determinants should be present and further studies on invasion mechanisms are needed.A toxigenic strain of the O139 serogroup carrying the ctxAB and belonging to the epidemic clonal branch is identified,which carries a multi-drug resistant plasmid.It is suggested that the O139 strain,which generally causes diarrhea,is also likely to become invasive when infecting individuals with underlying diseases.In general,these strains with invasive infections are not highly resistant to antibiotics.Although some strains are multi-drug resistant,multiple antibiotic options are available for clinical treatment.Our study suggests that both public health and clinical attention should be given to the problem of community-acquired V.cholerae invasive infections in patients with underlying disease,with serious prognosis. |
