Cause Of Bloodstream Infections Research Articles

#2276 Blood stream infections in patients with ANCA-associated vasculitis—a Danish nationwide study

Abstract Background and Aims Infection due to the immunosuppressive treatment, is among the most frequent causes of hospitalization and death in patients with ANCA-associated vasculitis (AAV). Information on prevailing causal microbial aetiologies is crucial for improving treatment and prevention of such events. Here we examined causal bacteriology, incidence, and risk of blood stream infections (BSIs) in incident and prevalent AAV patients, as compared to the general population. Method All data were retrieved from the Danish nationwide registries and the Danish Microbiology Database. Prevalent patients between 1998-2010 were all included at the same index date 1.1.2010; Incident patients diagnosed after 2010 were included with index being the day of diagnosis. Both groups were followed until first time BSI, death, or a maximum of 12 months. Background controls were matched 1:4 on age and sex. Cumulative incidence was assessed by the Aalen-Johansen estimator, and cox analyses adjusted for age, sex, kidney involvement, hypertension, diabetes, dialysis, and plasma exchange (PLEX), were used to model survival time. Results A total 19 (2.3%) BSIs were identified in 818 prevalent patients, and 55 (5.9%) BSIs in 939 incident patients (P < 0.001). As in the background control group, primary causal microbial agents among prevalent patients were E. coli (26.3%) and S. aureus (21.1%), with an overall Gram-negative predominance (58.8%). E. coli (17.5%) remained the most frequent microbial cause of BSIs in incident patients, however with a relatively higher frequency of gram-positive bacteria (50.9%) dominated by Coagulase-negative Staphylococci (12.3%), Enterococci (14%), and Streptococci (14%). Difference in bacteriology between prevalent and incident patients disappeared when patients on dialysis were excluded, whereas the difference in BSI frequency remained significant (p < 0.001). One-year HR of first-time BSI was significantly higher in patients with AAV as compared to controls (prevalent AAV: HR 3.17 [95% CI 1.63-6.18], p < 0.0001; Incident AAV; HR 8.64 [95% CI 4.88-15.31], p < 0.0001), with significant difference between incident and prevalent patients (HR 2.73 [95% CI 1.39-5.35], p = 0.003). Dialysis (HR 3.15 [95% CI 1.86-5.31], p < 0.0001) and PLEX (HR 1.87 [95% CI 1.05-3.33], p < 0.033) were solitary risk factors of BSI as well as higher age, hypertension, diabetes, and kidney disease (Figure). Risk of BSI remained significantly increased for both prevalent and incident patients as compared to matched background controls when patients on dialysis were excluded. Conclusion E. coli and S. aureus were predominant causal isolates in prevalent AAV patients and controls, and the gram-positive predominance seen with incident AAV was primarily caused by patients on dialysis. Risk of BSI was higher in incident AAV as compared to prevalent AAV, and the AAV diagnosis was associated with increased risk of BSI at all times, with highest risk initially after first diagnosis. Interventions requiring a central venous catheter were solitary risk factors of BSI.

Deletion of codY impairs Staphylococcus epidermidis biofilm formation, generation of viable but non-culturable cells and stimulates cytokine production in human macrophages.

Introduction. Staphylococcus epidermidis biofilms are one of the major causes of bloodstream infections related to the use of medical devices. The diagnosis of these infections is challenging, delaying their treatment and resulting in increased morbidity and mortality rates. As such, it is urgent to characterize the mechanisms employed by this bacterium to endure antibiotic treatments and the response of the host immune system, to develop more effective therapeutic strategies. In several bacterial species, the gene codY was shown to encode a protein that regulates the expression of genes involved in biofilm formation and immune evasion. Additionally, in a previous study, our group generated evidence indicating that codY is involved in the emergence of viable but non-culturable (VBNC) cells in S. epidermidis.Gap statement/Hypothesis. As such, we hypothesized that the gene codY has have an important role in this bacterium virulence.Aim. This study aimed to assess, for the first time, the impact of the deletion of the gene codY in S. epidermidis virulence, namely, in antibiotic susceptibility, biofilm formation, VBNC state emergence and in vitro host immune system response.Methodology. Using an allelic replacement strategy, we constructed and then characterized an S. epidermidis strain lacking codY, in regards to biofilm and VBNC cell formation, susceptibility to antibiotics as well as their role in the interaction with human blood and plasma. Additionally, we investigate whether the codY gene can impact the activation of innate immune cells by evaluating the production of both pro- and anti-inflammatory cytokines by THP-1 macrophages.Results. We demonstrated that the deletion of the gene codY resulted in biofilms with less c.f.u. counts and fewer VBNC cells. Furthermore, we show that although WT and mutant cells were similarly internalized in vitro by human macrophages, a stronger cytokine response was elicited by the mutant in a toll-like receptor 4-dependent manner.Conclusion. Our results indicate that codY contributes to S. epidermidis virulence, which in turn may have an impact on our ability to manage the biofilm-associated infections caused by this bacterium.

Strain Differences in Bloodstream and Skin Infection: Methicillin-Resistant Staphylococcus aureus Isolated in 2018-2021 in a Single Health System.

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8-sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018-2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs.

Clinical analysis of bacterial infection characteristics in lymphoma patients with high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation-a single-centered retrospective study.

High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation. To characterise pathogenic bacterial infections in HDT/AHSCT-treated lymphoma patients. The prevalence of pathogenic microorganisms and the timing of foci after transplantation, along with bloodstream infection (BSI) risk factors, can help determine the need for empirical antibiotics after AHSCT. We retrospectively analyzed 133 lymphoma patients treated by HDT/AHSCT from April 2017 to October 2021 at Peking University International Hospital, Beijing, China. We analyzed their clinical characteristics, microbiological distribution characteristics, and BSI risk factors in detail. In order, intestinal infection (56 cases), BSI (17 cases), pulmonary (12 cases), upper respiratory tract (5 cases), and perianal (4 cases) were the most common locations of infection after HDT/AHSCT. The infection sites yielded 92 putative pathogenic pathogens, with bacteria predominating (61.96%), fungi (28.26%), viruses (5.43%), and mycoplasma (4.35%). Gram-negative bacteria (GNB) strains outnumbered gram-positive bacteria (GPB) strains (73.68%). Two strains of Escherichia coli produced extended-spectrum β-lactamase (ESBL) and one strain of carbapenem-resistant enterobacteriaceae (CRE). Methicillin-resistant Staphylococcus epidermidis (MRSE) had one strain. BSI was caused by Escherichia coli (82.35%), Intestinal mucositis (23.52%), and catheter-associated infections (11.76%). Age, CD34, pretreatment regimen, antibiotic regimen, and past chemotherapeutic agent lung damage were BSI risk variables in univariate analysis. CD34 and past chemotherapeutic drug lung damage were the primary causes of BSI after HDT/AHSCT for lymphoma. High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study

Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shockcriteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A,B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. Instituto de Salud Carlos III.

ANTIMICROBIAL RESISTANCE IN SALMONELLA ENTERICA SEROVAR TYPHI: UNDERSTANDING THE MECHANISMS AND PATHOGENICITY OF INFECTION” A COMPREHENSIVE REVIEW

Typhoid Fever is a contagious disease caused by Salmonella enterica serovar typhi. It is also the cause of bloodstream infections in most of the developing countries. The pathogen can escape from the host’s immune response, a feature linked with the capsular structure of bacteria, which contributes to its virulence and is a crucial factor in the dissemination of infection. Salmonella enterica serovars are classified as typhoidal and nontyphoidal salmonella. In this review, we will discuss the ecumenical occurrence of immune strains of Salmonella enterica. We cover the mechanism of antimicrobial resistance in Salmonella, including plasmid-mediated resistance. Antibiotic resistance can occur through various mechanisms, such as deactivation of antibacterial medications, changes in therapeutic targets, and acquisition of foreign DNA coding for resistance determinants through horizontal gene transfer. Additionally, bacteria can employ different efflux pumps to resist antibiotics. These are some of the common ways in which antibiotic resistance is developed. We will explore the factors contributing to its virulence, such as the improper use of antibiotics, gene transfers, recurrent infections, and reduced host immunity. Proper hygiene practices and accurate treatment are necessary to combat typhoid disease, which can be better understood by studying its pathogenesis and diagnosis. The widal test and Typhidot test are essential for the diagnosis of salmonella. Vaccines are available against typhoid. We can overcome disease development through vaccination by choosing safe delivery methods and control strategies.

Bloodstream Infections in Pediatric Oncology Patients: Bacterial Pathogen Distribution and Antimicrobial Susceptibility at the University Hospital Centre Zagreb, Croatia-A 5-Year Analysis.

The epidemiology of bacterial pathogens causing bloodstream infections (BSIs) in pediatric hematology/oncology patients is changing and resistance to antimicrobial agents is globally spread. We retrospectively assessed demographic, clinical, and microbiologic data of BSIs during a 5-year period at a pediatric hematology/oncology unit from January 1, 2017, to December 31, 2021, at the University Hospital Centre Zagreb, Zagreb, Croatia. In 66 pediatric patients with malignancies, 93 BSI episodes were registered and 97 bacterial isolates were cultured. The Gram-positive versus Gram-negative ratio was 67 (69.1%) versus 30 (30.9%). Coagulase-negative staphylococci (48; 49.6%) were the most frequent isolates, followed by Enterobacterales (17; 17.5%) and Staphylococcus aureus (6; 6.2%). Multidrug resistance isolates included extended spectrum β-lactamase producers (n=3). Resistance rates to piperacillin/tazobactam, cefepime, and meropenem in Gram-negative isolates were 15.4%, 14.3%, and 0.0%, respectively. Gram-positive bacteria are the most common cause of BSI in our patients. Resistance rates to piperacillin/tazobactam and cefepime in Gram-negative isolates make meropenem a better choice for empirical antimicrobial treatment. As national and hospital data may differ, the surveillance of pathogen distribution and antimicrobial susceptibility in pediatric hematology/oncology wards is necessary to adjust empirical treatment accordingly.

Phenotypic and Genotypic Assays to Evaluate Coagulase-Negative Staphylococci Biofilm Production in Bloodstream Infections.

Coagulase-negative staphylococci (CoNS) are commensal on human body surfaces and, for years, they were not considered a cause of bloodstream infection and were often regarded as contamination. However, the involvement of CoNS in nosocomial infection is increasingly being recognized. The insertion of cannulas and intravascular catheters represents the primary source of CoNS entry into the bloodstream, causing bacteremia and sepsis. They owe their pathogenic role to their ability to produce biofilms on surfaces, such as medical devices. In this study, we evaluate the adhesive capacity of CoNS isolated from blood cultures by comparing a spectrophotometric phenotypic assay with genotypic analysis based on the evidence of the ica operon. We retrospectively reviewed the database of CoNS isolated from blood cultures from January to December 2021 that were considered responsible for 361 bloodstream infections. Eighty-nine CoNS were selected among these. Our data show that Staphylococcus epidermidis was the predominant species isolated, expressing greater adhesive capacities, especially those with the complete operon. Knowledge of the adhesive capabilities of a microorganism responsible for sepsis can be useful in implementing appropriate corrective and preventive measures, since conventional antibiotic therapy cannot effectively eradicate biofilms.

620. Development and Validation of a Novel qPCR Assay for Differentiation of Common Candida Pathogens including C. auris

Abstract Background Candida is a common asymptomatic fungal colonizer of humans. Of the 200+ total species in the genus Candida, only a few are known to cause infection. The most common are C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. auris. In the USA, candidemia is the fourth most common cause of bloodstream infections in hospitalized patients. Although antifungal medication can treat candidemia, mortality rates remain between 30 and 60%. Eurofins Viracor has developed a qPCR assay that will qualitatively detect and differentiate any of the 6 previously listed Candida species in whole blood. Speciation is critical for treatment due to variable drug susceptibility among different species, particularly C. auris due to its multi-drug resistance. Methods Multiple primer/probe mixes were designed around and within the ITS1, 5.8s, ITS2, and 28s ribosomal subunit regions in each of the six Candida target species. The 5.8s and 28s regions are heavily conserved, while the ITS regions are highly divergent and used to differentiate species. After optimization, the six primer/probe mixes were partially multiplexed resulting in four mixes covering all species. DNA was extracted from human blood spiked with viable Candida using the MagMAX™ DNA Multi-Sample Ultra 2.0 Kit, and eluates were amplified using the Applied Biosystems™ 7500 Fast platform. Results Each assay met all validation acceptance criteria and demonstrated excellent accuracy, precision, linearity and dynamic range, and sensitivity. 32 non-Candida fungal and bacterial pathogens that commonly cause bloodstream infections were used to assess specificity. All specificity samples were negative for all Candida targets. To assess accuracy, 75 of 75 Candida samples representing all six species across a range of concentrations were tested and correctly identified. 24 of 25 known-negative samples were negative, with one positive C. glabrata CT result observed just below the cutoff. Conclusion Traditional blood culture methods for Candida species identification can be too time consuming for a quickly progressing infection. The Candida qPCR assay described here not only detects an infection faster but provides accurate speciation allowing for rapid and targeted antifungal treatment options for the patient. Disclosures Clayton Thomas, BS in Biology, Eurofins Viracor: Employee James Grantham, n/a, Eurofins Viracor: Employee Emily Lute, n/a, Eurofins Viracor: Employee Jerod Davidson, n/a, Eurofins Viracor: Employee Scott Cowden, MS, MB ASCP(CM), Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK.

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases.

Risk Factors and Outcome of Gram-Negative Bloodstream Infection in Living-Donor Renal Transplant Recipients: A Case-Control Study From Pakistan.

Gram-negative rods are the most common cause of bloodstream infection in renal transplant recipients. Acute rejection, urologic abnormalities, and ureteral stents are risk factors. Graft dysfunction is independently associated with gram-negative rod bloodstream infection. Our aim is to investigate the incidence, risk factors, and outcome among living donor renal transplant recipients from Pakistan. In this case-control study, we reviewed the medical records until June 2021 of renal transplant recipients seen from 2015 to 2019 for gram negative bacteremia. For every case, controls were matched by age, date of transplant, and sex. Demographics, risk factors, graft function, and mortality were compared. Clinical features, immunosuppression, source of blood stream infection, and microbiology were noted in cases. Of 1677 renal transplant recipients, 44 developed gram negative bacteremia. The incidence was 5.9 per 1000 person-years. Median time since transplant was 5 months. The most common source was urinary tract infection. On univariate analysis, antithymocyte globulin, urinary tract infection, and recurrent urinary tract infections were associated with gram negative bacteremia. On multivariate analysis, urinary tract infection (adjusted odds ratio = 3.46; 95% CI, 1.27-9.37) and recurrent urinary tract infections (adjusted odds ratio = 4.03; 95% CI, 1.15-14.15) were significant risk factors. We found no difference in 30-day mortality and estimated glomerular filtration rate on last follow-up between cases and controls. Kaplan-Meier survival curves showed significant differences in graft survival in patients with gram negative bacteremia. Escherichia coli was the most common organism, with 75% ceftriaxone and 13% imipenem resistance. The most significant risk factor for gram negative rod bloodstream infection was recurrent urinary tract infections. Timely treatment and prevention of recurrent urinary tract infections areimperative for prevention of gram negative bacteremia.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Hyperendemic carbapenem-resistant Acinetobacter baumannii at a hospital in Botswana: Insights from whole-genome sequencing

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major cause of bloodstream infection among hospitalized patients in low- and middle-income countries (LMICs). CRAB infections can be difficult to treat and are devastating in neonates (~30% mortality). CRAB outbreaks are hypothesized to arise from reservoirs in the hospital environment, but outbreak investigations in LMICs seldom incorporate whole-genome sequencing (WGS). Methods: WGS (Illumina NextSeq) was performed at the National Institute for Communicable Diseases (South Africa) on 43 preserved A. baumannii isolates from a 530-bed referral hospital in Gaborone, Botswana, from March 2021–August 2022. This included 23 blood-culture isolates from 21 unique patients (aged 2 days–69 years) and 20 environmental isolates collected at the 36-bed neonatal unit in April–June 2021. Infections were considered healthcare-associated if the culture was obtained &gt;72 hours after hospital arrival (or sooner in inborn infants). Blood cultures were incubated using an automated system (BACT/ALERT, BioMérieux) and were identified using manual methods. Environmental isolates were identified using selective or differential chromogenic media (CHROMagarTM). Taxonomic assignment, multilocus sequence typing (MLST), antimicrobial resistance gene identification, and phylogenetic analyses were performed using publicly accessible analysis pipelines. Single-nucleotide polymorphism (SNP) matrices were used to assess clonal lineage. Results: All 23 blood isolates and 5 (25%) of 20 environmental isolates were confirmed as A. baumannii; thus, 28 A. baumannii isolates were included in the phylogenetic analysis. MLST revealed that 22 (79%) of 28 isolates were sequence type 1 (ST1), including all 19 healthcare-associated blood isolates and 3 (60%) of 5 environmental isolates. Genes encoding for carbapenemases (blaNDM-1, blaOXA-23) and biocide resistance (qacE) were present in all 22 ST1 isolates; colistin resistance genes were not identified. Phylogenetic analysis of the ST1 clade demonstrated spatial clustering by hospital unit. Related isolates spanned wide ranges in time (&gt;1 year), suggesting ongoing transmission from environmental sources (Fig. 1). An exclusively neonatal clade (0–2 SNPs) containing all 8 neonatal blood isolates was closely associated with 3 environmental isolates from the neonatal unit: a sink drain, bed rail, and a healthcare worker’s hand. Conclusions: WGS analysis of clinical and environmental A. baumannii revealed the presence of unit-specific CRAB clones, with evidence of ongoing transmission likely driven by persistent environmental reservoirs. This research highlights the potential of WGS to detect hospital outbreaks and reaffirms the importance of environmental sampling to identify and remediate reservoirs (eg, sinks) and vehicles (eg, hands and equipment) within the healthcare environment.Disclosures: None

Staphylococcus aureus bloodstream infection in a Chinese tertiary-care hospital: A single-center retrospective study.

Staphylococcus aureus bloodstream infection in a Chinese tertiary-care hospital: A single-center retrospective study.

Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

Health itinerary-related survival of children under-five with severe malaria or bloodstream infection, DR Congo.

Prompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death. Health itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - <5 years) admitted with suspected bloodstream infection to Kisantu district hospital, DR Congo. The cohort was followed until discharge to assess in-hospital death. From 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector. Long health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality. NCT04289688.

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases.

Porcine extraintestinal pathogenic Escherichia coli delivers two serine protease autotransporters coordinately optimizing the bloodstream infection.

Extraintestinal pathogenic Escherichia coli (ExPEC) is one of the leading causes of bloodstream infections in a broad spectrum of birds and mammals, thus poses a great threat to public health, while its underlying mechanism causing sepsis is not fully understood. Here we reported a high virulent ExPEC strain PU-1, which has a robust ability to colonize within host bloodstream, while induced a low level of leukocytic activation. Two serine protease autotransporters of Enterobacteriaceae (SPATEs), VatPU-1 and TshPU-1, were found to play critical roles for the urgent blood infection of strain PU-1. Although the Vat and Tsh homologues have been identified as virulence factors of ExPEC, their contributions to bloodstream infection are still unclear. In this study, VatPU-1 and TshPU-1 were verified to interact with the hemoglobin (a well-known mucin-like glycoprotein in red blood cell), degrade the mucins of host respiratory tract, and cleave the CD43 (a major cell surface component sharing similar O-glycosylated modifications with other glycoprotein expressed on leukocytes), suggesting that these two SPATEs have the common activity to cleave a broad array of mucin-like O-glycoproteins. These cleavages significantly impaired the chemotaxis and transmigration of leukocytes, and then inhibited the activation of diverse immune responses coordinately, especially downregulated the leukocytic and inflammatory activation during bloodstream infection, thus might mediate the evasion of ExPEC from immune clearance of blood leukocytes. Taken together, these two SPATEs play critical roles to cause a heavy bacterial load within bloodstream via immunomodulation of leukocytes, which provides a more comprehensive understanding how ExPEC colonize within host bloodstream and cause severe sepsis.

Streptococcus dysgalactiae Bloodstream Infections, Norway, 1999-2021.

Streptococcus dysgalactiae increasingly is recognized as a pathogen of concern for human health. However, longitudinal surveillance data describing temporal trends of S. dysgalactiae are scarce. We retrospectively identified all β-hemolytic streptococcal bloodstream infections reported in Bergen, in western Norway, during 1999-2021. To explore S. dysgalactiae disease burden in a broader context, we mapped the incidence of all microbial species causing bloodstream infections during 2012-2021. We found S. dysgalactiae incidence rates substantially increased during the study period; by 2021, S. dysgalactiae was the fifth most common pathogen causing bloodstream infections in our region. We noted genotypic shifts and found that the rising trend was related in part to the introduction and expansion of the stG62647 emm-type. S. dysgalactiae is among the most common causes of bloodstream infections in western Norway, and increased surveillance and unambiguous species identification are needed to monitor the disease burden attributable to this pathogen.

Coagulase-Negative Staphylococci in Neonatal Blood: How Concerning?

Objective Coagulase-negative staphylococci (CoNS) are being implicated as one of the leading causes of bloodstream infection (BSI). To study the spectrum, prevalence, and antimicrobial susceptibility of CoNS causing BSI in neonates. Materials and Methods A cross-sectional study was done in level III neonatal intensive care unit (NICU). Blood samples in automated culture bottles were processed as per the standard technique. Previously validated methods were followed for the characterization of CoNS and for AST of standard antibiotics by Kirby Bauer disk diffusion and vancomycin by agar dilution. The prevalence of causative organisms and susceptibility of CoNS were statistically analyzed. Categorical variables were compared by chi-square or Fisher's exact probability tests. Result In total, 1,365 blood samples (1,365 neonates) were studied, of which 383 (28.05%) were positive and 982 (71.94%) were negative. Gram-positive organisms (GPC) predominated ( n = 238; 62.14%) ( p < 0.001) with 41.77% (160/383) S. aureus and 13.83% (53/383) CoNS. CoNS included S. epidermidis (19, 38%), S . haemolyticus (7, 14%), S. hominis (6, 12%), S. simulans (6,12%), S. capitis (5,10%), S. cohnii (4, 8%), S. warneri (1, 2%), and S. xylosus (1, 2%). The susceptibility to netilmicin, linezolid, and vancomycin was 100% ( p ≤ 0.001), and 54% ( n = 27) had vancomycin MIC of 0.125 μg/mL but methicillin-resistant CoNS (MRCoNS) was 70%. Methicillin-susceptible (MS) CoNS had lower MIC of vancomycin ( p < 0.05) than MRCoNS. Conclusion The spectrum of pathogens causing BSI in neonates is changing with predominance of GPC and among CoNS, S. epidermidis . Considerable proportion of MRCoNS with the emergence of MIC creep for vancomycin requires immediate attention.