Bloodstream Infection In China Research Articles

Species Distribution, Typical Clinical Features and Risk Factors for Poor Prognosis of Super-Elderly Patients with Bloodstream Infection in China.

Bloodstream infection (BSI) is characterized by high mortality, especially among these increasing super-elderly patients (≥85 years), and this study was conducted to understand the species distribution, typical clinical features and risk factors for poor prognosis of super-elderly patients with BSI. Based on previous work, this retrospective study was performed by reviewing an ongoing prospective medical database in a comprehensive tertiary center in China, and all super-elderly patients with BSI in the past 6 years were enrolled in this study. Out of 5944 adult-patients with BSI, there were totally 431 super-elderly patients (≥85 years old) enrolled in this study and age ≥90 years accounted for 31.1% (134/431). Among these 431 super-elderly patients with BSI, 40 patients (9.3%) were diagnosed with BSI and the remained 401 super-elderly patients (90.7%) were defined as hospital-acquired BSI. The typical feature of these super-elderly patients with BSI was the high proportion of patients with various comorbidities, such as cardiovascular disease (83.8%), ischemic cerebrovascular disease (63.3%) and pulmonary infection (61.0%). The other typical feature was that most (60.1%) of these patients had been hospitalized for long time (≥28 days) prior to the onset of BSI, and most patients had received various invasive treatments, such as indwelling central venous catheter (53.1%) and indwelling urinary catheter (47.1%). Unfortunately, due to these adverse features above, both the 7-day short-term mortality (13.2%, 57/431) and the 30-day long-term mortality (24.8%, 107/431) were high. The multivariate analysis showed that both chronic liver failure (OR 7.9, 95% CI 2.3-27.8, P=0.001) and indwelling urinary catheter (OR 2.3, 95% CI 1.1-4.7, P=0.023) were independent risk factors for 7-day short-term mortality, but not for 30-day long-term mortality. In addition, the microbiology results showed that the most common species were associated with nosocomial infection or self-opportunistic infection, such as Staphylococcus hominis (18.3%), Staphylococcus epidermidis (11.8%), Escherichia coli (9.7%), Klebsiella pneumoniae (9.3%) and Candida albicans (8.6%, fungi). Super-elderly patients with BSI had typical features, regardless of the pathogenic species distribution and their drug resistance, or clinical features and their risk factors for poor prognosis. These typical features deserved attention and could be used for the prevention and treatment of BSI among super-elderly patients.

Genome sequence of a tigecycline-resistant Acinetobacter seifertii recovered in human bloodstream infection in China

The phylogenetic characteristics of Acinetobacter seifertii clinical strain are not well-studied. Here, we reported one tigecycline-resistant ST1612PasteurA. seifertii isolated from bloodstream infections (BSI) in China. Antimicrobial susceptibility tests were conducted via broth microdilution. Whole-genome sequencing (WGS) was performed and annotation was conducted using rapid annotations subsystems technology (RAST) server. Multilocus sequence typing (MLST), Capsular polysaccharide (KL) and lipoolygosaccharide (OCL) were analyzed using PubMLST and Kaptive. Resistance genes, virulence factors and comparative genomics analysis were performed. Cloning, mutations of efflux pump related genes and expression level were further investigated. The draft genome sequence of A. seifertii ASTCM strain is made up of 109 contigs with a total length of 4,074,640 bp. Based on the RAST results, 3,923 genes that belonged to 310 subsystems were annotated. A. seifertii ASTCM was ST1612Pasteur with KL26 and OCL4, respectively. It was resistant to gentamicin and tigecycline. ASTCM harbored tet(39), sul2 and msr(E)-mph(E) and one amino acid mutation in Tet(39) (T175A) was further identified. Nevertheless, the signal mutation failed to contribute to susceptibility change of tigecycline. Of note, several amino acid substitutions were identified in AdeRS, AdeN, AdeL and Trm, which could lead to overexpression of adeB, adeG, and adeJ efflux pump genes and further possibly lead to tigecycline resistance. Phylogenetic analysis showed a huge diversity was observed among A. seifertii strains based on 27-52,193 SNPs difference. In summary, we reported a tigecycline-resistant ST1612PasteurA. seifertii in China. Early detection is recommended to prevent their further spread in the clinical setting.

Genotypic characterization of a Proteus mirabilis strain harboring blaKPC-2 on the IncN plasmid isolated from a patient with bloodstream infection in China

BackgroundCarbapenemase is the predominant enzyme in the mechanism leading to Enterobacterales resistance to carbapenems, and the rapid spread of the blaKPC gene is a major public health concern. Here, we describe a carbapenem-resistant Proteus mirabilis strain XH983, which harbored a blaKPC-2-producing IncN plasmid, isolated from a bloodstream infection. MethodsWhole-genome sequencing and bioinformatics analysis were performed to assess the genetic environment of P. mirabilis XH983. Conjugation and transfer experiments were performed and the corresponding strains were confirmed by antimicrobial susceptibility testing. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant P. mirabilis isolates worldwide. ResultsP. mirabilis XH983 was isolated from the blood of a patient in Hangzhou, China. The genome of XH983 contained one 4128,916 bp circular chromosome and one 24,225 bp IncN plasmid harboring blaKPC-2. P. mirabilis XH983 had multiple resistance genes, conferring resistance to aminoglycosides [aph(3')-Ia, aph(3'')-Ib, aph(6)-Id, aac(3)-IId, aadA5, aadA1], β-lactams (blaKPC-2, blaTEM-1B), phenicol (cat, catA1), sulphonamide/trimethoprim (drfA1, drfA17, sul1, sul2) and tetracycline [tet(J)]. The phylogenetic tree showed that XH983 was present in a cluster of 30 isolates, all of which carried blaKPC-2 and most of them came from the same hospital as XH983, indicating the clonal spread of the cluster. ConclusionWe characterized carbapenem-resistant P. mirabilis clinical isolate XH983. The genome sequence of P. mirabilis XH983 provides information about resistance mechanisms of P. mirabilis carrying the blaKPC-2 plasmid and the potential spread of blaKPC-2.

Characterization of the First Carbapenem-Resistant Pseudocitrobacter faecalis Harboring blaOXA-181 in China

With the wide use of carbapenems, carbapenem-resistant Enterobacterales have been increasingly reported worldwide. In this study, one blaOXA-181-positive Pseudocitrobacter faecalis strain was isolated from the blood culture of a patient with a bloodstream infection in China, which was its first clinical report outside Pakistan. Species identification of P. faecalis was initially performed using MALDI-TOF/MS and further confirmed by 16S rRNA gene and housekeeping gene sequencing. The antimicrobial susceptibility testing was determined through the broth microdilution method, and their clonal relationship was analyzed by pulsed-field gel electrophoresis. To study the transmission and genetic structure of the blaOXA-181 gene, a transformation test and whole-genome sequencing (WGS) were performed. The results of the antimicrobial susceptibility testing indicated this P. faecalis was resistant to carbapenems, quinolones, and commonly used β-lactam/β-lactamase inhibitor combinations. Through WGS and transformation experiments, blaOXA-181 and qnrS1 genes causing antibiotic resistance were located on a 55,148-bp length IncX3 type plasmid with a truncated ColKp3 replicon gene. As a rare species of Enterobacterales, P. faecalis was clinically reported in China for the first time, and the blaOXA-181 gene it carried was located on a globally disseminated IncX3 plasmid. The spread of such bacteria and antibiotic resistance requires more clinical attention.

Coexistence of two blaCTX-M-14 genes in a blaNDM-5-carrying multidrug-resistant Escherichia coli strain recovered from a bloodstream infection in China

The emergence of carbapenem-resistant Enterobacteriaceae has become a serious public-health threat. Here we report the complete genome sequence of a multidrug-resistant (MDR) Escherichia coli carrying blaNDM-5 and two copies of blaCTX-M-14 recovered from a bloodstream infection in China. Whole-genome sequencing of E. coli strain 2D was performed both using Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms. De novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicons were identified from the genome sequence. Core genome MLST (cgMLST) analysis between E. coli 2D and all ST354 E. coli strains retrieved from the NCBI GenBank database was performed using BacWGSTdb 2.0 server. The complete genome sequence of E. coli 2D consists of six contigs comprising 5 363 300 bp, including one chromosome and five plasmids, and was assigned to ST354. Six antimicrobial resistance genes were identified, including blaNDM-5 located in a 46 161-bp IncX3 plasmid and two copies of the blaCTX-M-14 gene located both in the chromosome and in a 96 499-bp IncB plasmid. The closest relative of E. coli 2D was another isolate recovered from Lebanon, which differed by 162 cgMLST loci. This study reports the first genome sequence of a MDR E. coli carrying blaNDM-5 and two copies of blaCTX-M-14 in China. These data may help to understand the antimicrobial resistance mechanisms and transmission dynamics of carbapenem-resistant Enterobacteriaceae in clinical settings.

Genotypic and phylogenetic characterisation of a clinical Ralstonia pickettii strain carrying two novel OXA allelic variants, blaOXA-898 and blaOXA-899, isolated from a bloodstream infection in China

ObjectivesRalstonia pickettii has been increasingly recognised as an emerging opportunistic pathogen in hospital settings in recent years, especially in patients with prolonged hospital stay. Clinical manifestations associated with R. pickettii infection range from mild infections to severe invasive life-threatening infections. Here we report the genome sequence of a clinical R. pickettii strain (PSLESD1) carrying two novel blaOXA allelic variants in China. MethodsWhole-genome sequencing of strain PSLESD1 was performed using an Illumina NovaSeq 6000 platform. Antimicrobial resistance genes were identified using the BacWGSTdb server. The phylogenetic relationship betweenR. pickettii PSLESD1 and a total of 17 R. pickettii strains deposited in the NCBI GenBank database was analysed using NJ (neighbour joining)/UPGMA (unweighted pair-group method with arithmetic mean) phylogeny (MAFFT v.7) based on core genome single nucleotide polymorphism (SNP) data. ResultsThe draft genome sequence of R. pickettii strain PSLESD1 consists of 25 contigs comprising 5 267 333 bp. Three antimicrobial resistance genes were identified in the genome, including blaOXA-898, blaOXA-899 and sul2. Strain PSLESD1 was resistant to aminoglycosides and carbapenems including meropenem. Phylogenetic analysis showed that all strains retrieved from the NCBI GenBank database were epidemiologically unrelated. The closest relative of strain PSLESD1 was H2Cu2, which differed by 2908 SNPs. ConclusionIn summary, we report the first genome sequence of a clinicalR. pickettii strain harbouring two novel class D β-lactamase genes (blaOXA-898 and blaOXA-899) recovered from a bloodstream infection in China. These data may help to understand the genomic features and antimicrobial resistance mechanisms of this bacterial pathogen.

Characterization of an IMP-4-Producing Klebsiella pneumoniae ST1873 Strain Recovered from an Infant with a Bloodstream Infection in China.

PurposeImipenemase (IMP), an Ambler class B metallo-β-lactamase, is an important carbapenemase that confers resistance to almost all β-lactams. In this study, we characterized the genomic feature of an IMP-4-producing Klebsiella pneumoniae ST1873 strain, a rare sequence type (ST) isolated from an infant with a bloodstream infection in China.Patients and MethodsK. pneumoniae strain, BKP19, was collected from a bloodstream infection in an infant who was hospitalized at the department of paediatrics. The whole genome sequence of the strain was sequenced using the Illumina NovaSeq 6000 platform and long-read MinION sequencer. Multilocus sequence typing, antimicrobial resistance gene identification, plasmid and phylogenetic relationship analysis of the strain were analysed by various bioinformatics approaches.ResultsK. pneumoniae BKP19 was resistant to multiple antimicrobials, including carbapenems. Eleven antimicrobial resistance genes corresponding to beta-lactam resistance, quinolone resistance, phenicol resistance and fosfomycin resistance could be identified in the genome. The carbapenem resistance gene blaIMP-4 was located in an IS26-associated class 1 integron of an IncN-type plasmid with 39,033 bp (pIMP-4-BKP19). Sequence alignment revealed that pIMP-4-BKP19 is closely related to the common plasmid carrying IMP-4 in K. pneumoniae (pIMP-HZ1-like plasmid) but is smaller, lacking the quinolone resistance gene qnrS1 and multiple tra gene orthologs. Conjugation experiment revealed that pIMP-4-BKP19 is a non-conjugative plasmid. According to in silico MLST analysis, K. pneumoniae strain BKP19 belongs to a sporadic clone ST1873.ConclusionIn summary, our study reports the first genome sequence of a K. pneumoniae ST1873 strain harbouring the class B β-lactamase blaIMP-4 in an IncN-type plasmid recovered from an infant with a bloodstream infection in China. Considering the global emergence of IMP-4 carbapenemase, more attention must be paid to prevent its future prevalence.

Characterization of highly virulent community-associated methicillin-resistant Staphylococcus aureus ST9-SCCmec XII causing bloodstream infection in China

Previous studies have shown that livestock (LA)-MRSA ST398 evolved from a human-adapted methicillin-susceptible S. aureus (MSSA) clone. However, detailed information regarding ST9 is still unclear. Here, we characterized a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) ST9-SCCmec XII isolate that has not been previously reported to cause serious disease in China. We obtained whole-genome sequences of one ST9-t899-XII isolate—ZY462471—from a patient with bloodstream infection without livestock contact. The antibiotic susceptibilities of ZY462471 were determined and the clinical information was extracted from medical notes and compared with twenty-seven previously sequenced genomes. Phylogenetic reconstruction was performed to investigate the probable host evolutionary origins of ZY462471, and the difference in resistome and virulence factors were investigated. Virulence assay was performed to evaluate the high virulence potential of ZY462471 and compare the virulence between the closest ST9 MSSA neighbours. Clinical data suggested that ZY462471 is a CA-MRSA. Phylogenetic analysis showed a much closer relationship of ZY462471 with human-associated MSSA ST9 isolates than other LA-MRSA ST9 isolates, suggesting that ZY462471 probably evolved from ST9 MSSA predecessors by acquiring an SCCmec cassette. Importantly, virulence assays indicated that ZY462471 was highly virulent and compared with the MSSA ST9 predecessors, ZY462471 did not show attenuated virulence. Finally, we found that ZY462471 harboured an immune evasion cluster (IEC)-carrying βC-Φ, which is typically found in human clinical S. aureus rather than LA-MRSA isolates, suggesting that ZY4762471 obtained the IEC-carrying βC-Φs from human clinical S. aureus strains. Considering its high virulence potential, this strain should be monitored to prevent more widespread dissemination.

Prevalence and characteristics of pks gene cluster harbouring Klebsiella pneumoniae from bloodstream infection in China.

Bloodstream infection (BSI), caused by Klebsiella pneumoniae, is associated with high morbidity and mortality, where the pks gene cluster plays a major role in their occurrence and prevalence. Information on the prevalence and characteristics of this gene cluster in K. pneumoniae is currently limited in mainland China. We therefore undertook a multicentre longitudinal study which revealed the prevalence, overall, community-onset and hospital-acquired BSI to be 20.5%, 28.3% and 13.0%, respectively. Compared to pks-negative, pks-positive isolates were significantly more susceptible to antimicrobial agents with a low incidence (5.1%) of multidrug-resistance and with infrequent extended-spectrum beta-lactamase (ESBL) production. Among pks-positive isolates, ST23 (78/117) and ST65 (20/117) were the dominant sequence types, and the majority harboured virulence genes. Community-onset BSI patients infected with pks-positive isolates had a higher proportion of liver abscesses and a lower proportion of biliary obstructions (P < 0.05). The pks-positive isolates were mostly sporadic in the phylogenetic tree, with a 65.8 and 47.0 average allele difference between Clade 1 and Clade 2, respectively. We concluded that although pks-positive K. pneumoniae were generally susceptible to antimicrobials, the high prevalence of such isolates in community cases and the genotoxicity, merits further investigation.

Whole genome sequence of an Escherichia coli ST410 isolate co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr genes isolated from a patient with bloodstream infection in China.

Mortality associated with carbapenemase-producing Enterobacteriaceae is high as there are few therapeutic options. Escherichia coli sequence type 410 (ST410) is currently an international high-risk clone and is responsible for a large number of clinical infections. Here we report the draft genome sequence of a ST410 clinical E. coli isolate (ECS9) co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr genes, obtained from a patient with bloodstream infection in China. The genome of E. coli ECS9 was sequenced using an Illumina HiSeqTM 4000 instrument with a 150-bp paired-end approach. Generated sequence reads were assembled using Velvet 1.2.10. Contigs were annotated using Rapid Annotation using Subsystem Technology (RAST), and further whole-genome sequence data analyses were performed. Escherichia coli ECS9 belongs to multilocus sequence typing (MLST) ST410. The total number of assembled bases was 4 935 145 bp, with 5077 protein-coding sequences. The presence of the blaNDM-5, blaOXA-1, blaCTX-M-15 and blaCMY-2 genes was detected in addition to other antimicrobial resistance genes conferring resistance to fluoroquinolones, aminoglycosides, trimethoprim, sulfonamides and tetracyclines. To our knowledge, this is the first report of anE. coli ST410 strain co-harbouring blaNDM-5, blaOXA-1, blaCTX-M-15, blaCMY-2, aac(3)-IIa and aac(6')-Ib-cr, obtained from a bloodstream infection in China. The presented genome sequence of carbapenemase-producing E. coli strain ST410 could provide further insight into the acquisition of multiple resistance genes by this successful lineage.

Early use of polymyxin B reduces the mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection

Polymyxin B is one of the last resort option for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection in China. Therefore, the timing of administration of polymyxin is frequently delayed. We collected 40 cases of CRKP bloodstream infections (BSIs) treated with combinations based on polymyxin B over 30 months. The primary outcome, 30-day mortality rate, was 52.5% (21/40). Early administration of polymyxin B is meant to administer the drug within 48h of diagnosing bacteremia. Delayed administration was considered when polymyxin B was administered after 48h of bacteremia onset. Polymyxin B duration and total dosages were similar in the two groups (11.57 days versus 11.76 days, p=0.919; 1306.52mg versus 1247.06mg, p=0.711). Compared with delayed administration, early use of polymyxin B-based combination therapy had a significant increase in the rate of bacterial clearance (65.22% versus 29.41%, p=0.025; OR=0.533) and decreased 30-day mortality (39.13% versus 70.59%, p=0.045; OR=0.461) and overall mortality (43.48% versus 82.35%, p=0.022; OR=0.321).

Complete genome sequencing and genomic characterization of two Escherichia coli strains co-producing MCR-1 and NDM-1 from bloodstream infection

We previously described the discovery of two Escherichia coli isolates (EC1002 and EC2474) co-harbouring mcr-1 and blaNDM-1 genes, which were recovered from bloodstream infection in China. More importantly, these antibiotic resistance genes were located on different plasmids and signaling the potential spread of pandrug-resistant bacteria. Here, the complete genome sequences of both isolates were determined using Pacbio RS II and Illumina HiSeq2000 systems. The genome of EC1002 consists of a 5,177,501 base pair chromosome and four circular plasmids, while the genome of EC2474 consists of a 5,013,813 base pair chromosome and three plasmids. The plasmid replicon type of pEC1002_NDM and pEC2474_NDM were identified as IncA/C2 and IncF, respectively. The genetic environment of blaNDM-1 in this study was similar to blaNDM-carrying plasmids detected in China, although the overall nucleotide identity and query coverage were variable. The plasmid replicon type of pEC1002_MCR and pEC2474_MCR were identified as IncI2 and IncHI2, respectively. Two different genetic strategies for mcr-1 gene spread were observed in this study and blaNDM-1 genes were also found transferred by two different mobile genetic elements in two plasmids. The findings of this study further support that the diversified transfer mechanisms of blaNDM-1 and mcr-1 present in Enterobacteriaceae.

Virulence gene profiling and molecular characterization of hospital-acquired Staphylococcus aureus isolates associated with bloodstream infection

A better understanding of virulence gene profiling and molecular characterization of Staphylococcus aureus isolates associated with bloodstream infection (BSI) may provide further insights related to clinical outcomes with these infections. We analyzed 89 S. aureus isolates including 37 MRSA isolates (41.6%) recovered from 89 adult patients with BSI from 4 hospitals in Zhejiang province, eastern China. Thirty-five (94.6%) of MRSA isolates and 4 (7.7%) of methicillin-sensitive S. aureus (MSSA) isolates were resistant to multiple antimicrobials. All isolates harbored at least 2 of 22 possible virulence genes, including sdrC (92.1%), icaA (89.9%), hla (80.9%), clf (69.7%), sea (68.5%), sdrD (67.4%), hlb (67.4%), sdrE (65.2%), sei (51.7%), seg (50.6%), and cna (50.6%). Forty-four (49.4%) of all S. aureus BSI isolates, including 23 (62.2%) of MRSA isolates, harbored ≥10 of the virulence genes evaluated in this study. Sixteen (43.2%) MRSA isolates and 5 (9.6%) MSSA isolates harbored the gene encoding Panton–Valentine leukocidin (PVL). Collective genes for pvl, sdrE, sed, seg, and sei among MRSA isolates were significantly more frequent relative to MSSA isolates (P < 0.05). A total of 22 sequence types (STs), including novel ST2184, ST2199, and ST2200, and 33 spa types, including novel spa types t9530 and t9532, were identified among S. aureus BSI isolates, among which ST188 (15.7%) and ST7 (15.7%), and t091 (12.4%) and t189 (12.4%), seldom noted for Chinese isolates previously, were major STs and spa types, respectively. In contrast to previous reports, no predominant clones were found in the present study. Among the MRSA isolates, although ST239-MRSA-SCCmecIII, predominant clone in China, still represented the most common clone, it only accounted for 18.9%. However, ST188-MRSA- SCCmecIV seldom reported before accounted for 10.8%. Among the MSSA isolates, ST7-MSSA represented the most common clone (23.1%), followed by ST188-MSSA and ST630-MSSA (9.6% each). In conclusion, simultaneous carriage of multiple virulence genes and genetically considerable diversity were common among S. aureus BSI isolates. Furthermore, MRSA isolates exhibited more frequent carriage of superantigen genes and pvl relative to MSSA isolates. Taken together, there are distinctive virulence gene profiling and molecular characteristic among S. aureus isolates associated with bloodstream infection in China.