Bacterial Bloodstream Infections Research Articles

Prediction of carbapenem-resistant gram-negative bacterial bloodstream infection in intensive care unit based on machine learning

BackgroundPredicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2–5 days conventionally to return the results from doctor's order.MethodsIt is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture.ResultsThere were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively.ConclusionsThe machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Prior cytomegalovirus reactivation may lead to worse bacterial bloodstream infection outcomes in HSCT patients

BackgroundCytomegalovirus (CMV) reactivation is common after transplantation, and may further augment natural killer (NK) cell activity, which has a protective role through both innate and adaptive immune responses. Bacterial bloodstream infections (BBSIs) are a common cause of morbidity and mortality in patients following allo-HSCT. Therefore, we hypothesized that CMV reactivation might play a role in the outcomes of patients with BBSI after allo-HSCT. ObjectivesWe investigated the role of CMV reactivation in the clinical outcomes of patients with BBSI after allo-HSCT. Study designA total of 101 BBSI patients (45 non-CMV reactivation [NCR] and 56 CMV reactivation [CR]) were included in the study following allo-HSCT. Clinical and laboratory findings were reviewed, and differences were tested using the Chi-square (χ2) test. Multivariate Cox regression analysis was used to calculate hazard ratios for between-group comparisons of clinical outcomes. ResultsCMV reactivation had a negative prognostic impact on the clinical outcomes of BBSI patients following allo-HSCT with regard to the 1-year overall survival time (HR, 3.583; 95% CI, 1.347–9.533; P = 0.011). In 56 BBSI patients with CMV reactivation following allo-HSCT, the 1-year mortality among those in whom CMV was reactivated first (CRF) was significantly elevated (56.5% vs. 18.2%, P = 0.003) compared with patients in whom the BBSIs occurred first (BOF). ConclusionsCMV reactivation in BBSI patients is related to higher mortality 1-year after allo-HSCT. Further studies on a larger cohort are needed to better understanding the mechanism of CMV reactivation influence.

The causes of bacterial bloodstream infections and antimicrobial resistance patterns in children attending a secondary care hospital in Bhaktapur, Nepal, 2017-2022: a retrospective study.

Data on antimicrobial resistance (AMR) among children in Nepal are limited. Here we have characterized the causes of bacterial bloodstream infections (BSIs), antimicrobial resistance patterns and the mechanisms of β-lactamase production in Enterobacterales among children attending outpatient and inpatient departments of a secondary care paediatric hospital in Nepal. We retrospectively collected demographic and clinical data of culture-proven bacterial BSIs between January 2017 and December 2022 among children <18 years attending a 50-bedded paediatric hospital. Stored isolates were subcultured for antimicrobial susceptibility testing against commonly used antimicrobials. Enterobacterales displaying non-susceptibility to β-lactams were phenotypically and genotypically investigated for ESBLs, plasmid-mediated AmpC (pAmpC) β-lactamases and carbapenemases. A total of 377 significant bacteria were isolated from 27 366 blood cultures. Among 91 neonates with a BSI, Klebsiella pneumoniae (n = 39, 42.4%), Pseudomonas aeruginosa (n = 15, 16.3%) and Acinetobacter baumannii complex (n = 13, 14.1%) were most common. In the non-neonates, 275/285 (96.5%) infections were community-acquired including Staphylococcus aureus (n = 89, 32.4%), Salmonella Typhi (n = 54, 19.6%) and Streptococcus pneumoniae (n = 32, 11.6%). Among the 98 S. aureus, 29 (29.6%) were methicillin-resistant Staphylococcus aureus. K. pneumoniae and Escherichia coli demonstrated non-susceptibility to extended-spectrum cephalosporins and carbapenems in both community and hospital-acquired cases. For E. coli and K. pneumoniae, blaCTX-M (45/46), blaEBC (7/10) and blaOXA-48 (5/6) were common among their respective groups. We determined significant levels of AMR among children attending a secondary care paediatric hospital with BSI in Nepal. Nationwide surveillance and implementation of antimicrobial stewardship policies are needed to combat the challenge imposed by AMR.

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia

Staphylococcus aureus is the leading cause of death due to bacterial bloodstream infection. Female sex has been identified as a risk factor for mortality in S aureus bacteremia (SAB) in some studies, but not in others. To determine whether female sex is associated with increased mortality risk in SAB. MEDLINE, Embase, and Web of Science were searched from inception to April 26, 2023. Included studies met the following criteria: (1) randomized or observational studies evaluating adults with SAB, (2) included 200 or more patients, (3) reported mortality at or before 90 days following SAB, and (4) reported mortality stratified by sex. Studies on specific subpopulations (eg, dialysis, intensive care units, cancer patients) and studies that included patients with bacteremia by various microorganisms that did not report SAB-specific data were excluded. Data extraction and quality assessment were performed by 1 reviewer and verified by a second reviewer. Risk of bias and quality were assessed with the Newcastle-Ottawa Quality Assessment Scale. Mortality data were combined as odds ratios (ORs). Mortality at or before 90-day following SAB, stratified by sex. From 5339 studies retrieved, 89 were included (132 582 patients; 50 258 female [37.9%], 82 324 male [62.1%]). Unadjusted mortality data were available from 81 studies (109 828 patients) and showed increased mortality in female patients compared with male patients (pooled OR, 1.12; 95% CI, 1.06-1.18). Adjusted mortality data accounting for additional patient characteristics and treatment variables were available from 32 studies (95 469 patients) and revealed a similarly increased mortality risk in female relative to male patients (pooled adjusted OR, 1.18; 95% CI, 1.11-1.27). No evidence of publication bias was encountered. In this systematic review and meta-analysis, female patients with SAB had higher mortality risk than males in both unadjusted and adjusted analyses. Further research is needed to study the potential underlying mechanisms.

Frequency of microorganisms in children presenting with acute fever at the outpatient department.

Objective: To determine the incidence of blood stream bacterial infection and the frequency of microorganisms involved as evaluated by blood culture in children presenting with acute febrile illness at the outpatient department. Study Design: Cross-sectional study. Setting: Department of Pediatrics and Child Health, Mardan Medical Complex, Mardan, Pakistan. Period: 1st March 2023 to 31st of August 2023. Material &amp; Methods: A total of 252 children from both genders between the ages of 1 month to 15 years presented at outpatients department with fever (≥ 38.0 °C or 100.4 °F) for ˃ two days were included in the study using consecutive sampling technique. The blood cultures of these children were sent to the laboratory for investigations. Bacterial strains were isolated and identified using standard microbiological techniques. The primary outcome was to determine the incidence of blood stream bacterial infection and the frequency of microorganisms involved. Results: The Mean±SD of age is this study was 4.20±3.42 years with an age range of 0.5-14 years. Male gender was 51.59% while female gender was 48.41%. The results of blood culture report showed that bacterial growth was present in 37 (14.68%) of total study patients. Out of these positive blood cultures, Gram-positive Cocci was reported in 16 (43.24%) of the children while Gram-negative bacilli were present in 21 (56.76%). The prevalence of E Coli was highest in these children 10 (27.02%) followed by S Typhi 8 (21.62%), Streptococcus pneumonia 5 (13.51%) and S aureus 4 (10.81%). Conclusion: It was concluded that the Gram-negative bacilli are the common cause of bacterial infection in children presenting with fever at outpatient department of a tertiary care hospital in this region with most frequent presence of E Coli and S Typhi.

Carbapenem-resistant Klebsiella pneumoniae bloodstream infections in haematological malignances and hematopoietic stem cell transplantation: Clinical impact of combination therapy in a 10-year Brazilian cohort.

Bacterial bloodstream infections (BSI) are a common threat among patients with haematological malignancies (HM) and hematopoietic stem cell transplant recipients (HSCT). The purpose of this research was to describe clinical and microbiological aspects of BSI caused by carbapenem-resistant Klebsiella pneumoniae (CRKp) and assess risk factors associated with 30-day mortality in a 10-year cohort of haematological patients. A total of 65 CRKp-BSI episodes occurring in HM patients and HSCT recipients and CRKp-BSI between January 2010 and December 2019 were retrospectively studied. Acute leukemias were the most frequently observed underlying disease (87.7%) and 18 patients (27.7%) received HSCT. Mucosal barrier injury in the gastrointestinal tract was the primary cause of bacteremia (86.1%). Also, 14 individuals (21.6%) had an Invasive Fungal Disease (IFD) throughout the episode. Regarding treatment, in 31 patients (47.7%) empirical therapy was deemed appropriate, whereas 33 (50.8%) patients received a combination therapy. Microbiological data revealed that the majority of isolates (53-58%) had the Polymyxin B co-resistance phenotype, while amikacin resistance was less common (16 samples, or 24.7%). The mortality rates at 14 and 30 days were 32.3% and 36.9%, respectively. In a multivariate Cox regression analysis, prompt appropriate antibiotic administration within three days was associated with a better outcome (Adjusted Hazard Ratio [aHR]: 0.33; 95% Confidence Interval [CI]: 0.14-0.76; p = 0.01), whereas hypotension at presentation (aHR: 3.88; 95% CI: 1.40-10.74; p = 0.01) and concurrent IFD (aHR: 2.97; 95% CI: 1.20-7.37; p = 0.02) were independently associated with death within 30 days. Additionally, a favorable correlation between combination therapy and overall survival was found (aHR: 0.18; 95%CI: 0.06-0.56; p = 0.002). In conclusion, 30-day mortality CRKp-BSI was elevated and most of the isolates were polymyxin B resistant. Early appropriate antimicrobial treatment and the use of combination therapy were linked to a better outcome.

Antibody-Mediated Serum Resistance Protects Pseudomonas aeruginosa During Bloodstream Infections.

Pseudomonas aeruginosa is a frequent pathogen isolated from bacterial bloodstream infection (BSI) and is associated with high mortality. To survive in the blood, P aeruginosa must resist the bactericidal action of complement (ie, serum killing). Antibodies usually promote serum killing through the classical complement pathway; however, "cloaking antibodies" (cAbs) have been described, which paradoxically protect bacteria from serum killing. The relevance of cAbs in P aeruginosa BSI is unknown. Serum and P aeruginosa were collected from a cohort of 100 patients with BSI. Isolates were tested for sensitivity to healthy control serum (HCS). cAb prevalence was determined in sera. Patient sera were mixed with HCS to determine if killing of the matched isolate was inhibited. Overall, 36 patients had elevated titers of cAbs, and 34 isolates were sensitive to HCS killing. Fifteen patients had cAbs and HCS-sensitive isolates; of these patients, 14 had serum that protected their matched bacteria from HCS killing. Patients with cAbs were less likely to be neutropenic or have comorbidities. cAbs are prevalent in patients with P aeruginosa BSI and allow survival of otherwise serum-sensitive bacteria in the bloodstream. Generation of cAbs may be a risk factor for the development of BSI.

Single non-blood-related umbilical cord blood transplantation using a reduced-intensity conditioning regimen for the treatment of severe aplastic anemia

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using Escherichia coli clinical bloodstream isolate pairs (initial and relapse isolates) from patients with relapsed GNB-BSI, we found that 4/11 (36%) of the relapse isolates displayed a significant increase in persisters cells relative to the initial bloodstream infection isolate. In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of-function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo.

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients.

COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66-14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29-20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use.

Epidemiology, Microbiology, and Risk Factors of Bacterial Bloodstream Infections in Patients After Allogeneic Hematopoietic Stem Cell Transplantation.

To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment. This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed. Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32). BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.

Cytomegalovirus Reactivation in Severe Coronavirus Disease 2019: Case Series from a Tertiary Care Center in the Western State of India

Abstract Introduction: Cytomegalovirus (CMV) reactivation in patients who have been admitted to the intensive care unit (ICU) is linked to higher mortality and health-care costs. There is a dearth of published research on CMV reactivation in patients with severe SARS-CoV-2. Materials and Methods: Objectives: The objective of this study was to describe clinical and laboratory profiles and outcomes of CMV reactivation in patients with severe SARS-CoV-2 illness. In this retrospective study carried out at a tertiary care hospital ICU in the Western state of India, patients with severe SARS-CoV-2 who were admitted from January 1, 2021, to May 31, 2021, and who got CMV viral load testing by reverse transcriptase polymerase chain reaction were analyzed. Results: During the study period, 27 out of 277 admitted patients were subjected to plasma CMV viral load testing, of which 13 patients had detectable viral load giving a prevalence of 4.7%. Patients who tested positive for CMV had significantly higher mortality (P = 0.020) and ventilator support needs (P = 0.004). Both fungal and bacterial bloodstream infections were frequent in CMV-positive patients, but neither was statistically significant (P = 0.065 and P = 0.571, respectively). In this case series, there was no difference in CMV reactivations according to the degree of lymphopenia (P = 0.149), usage of steroids (P = 0.766), or immunomodulatory medications (tocilizumab/bevacizumab, P = 0.926). Conclusions: In SARS-CoV-2 patients with severe illness, CMV reactivation was associated with an increased need for ventilator support, a higher incidence of nosocomial infection (bacterial and fungal), and overall mortality.

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

Pediatric oncology patients with prolonged (≥96hours) febrile neutropenia (absolute neutrophil count<500/μL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74%vs 63%, p=0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

Metagenomic identification of pathogens and antimicrobial-resistant genes in bacterial positive blood cultures by nanopore sequencing.

Nanopore sequencing workflows have attracted increasing attention owing to their fast, real-time, and convenient portability. Positive blood culture samples were collected from patients with bacterial bloodstream infection and tested by nanopore sequencing. This study compared the sequencing results for pathogen taxonomic profiling and antimicrobial resistance genes to those of species identification and phenotypic drug susceptibility using traditional microbiology testing. A total of 37 bacterial positive blood culture results of strain genotyping by nanopore sequencing were consistent with those of mass spectrometry. Among them, one mixed infection of bacteria and fungi was identified using nanopore sequencing and confirmatory quantitative polymerase chain reaction. The amount of sequencing data was 21.89 ± 8.46 MB for species identification, and 1.0 MB microbial strain data enabled accurate determination. Data volumes greater than or equal to 94.6 MB nearly covered all the antimicrobial resistance genes of the bacteria in our study. In addition, the results of the antimicrobial resistance genes were compared with those of phenotypic drug susceptibility testing for Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. Therefore, the nanopore sequencing platform for rapid identification of causing pathogens and relevant antimicrobial resistance genes complementary to conventional blood culture outcomes may optimize antimicrobial stewardship management for patients with bacterial bloodstream infection.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

From Epidemiology of Community-Onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-Decision Algorithm in a Region with High Burden of Antimicrobial Resistance.

Antimicrobial-resistant (AMR) infections have increased in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and mortality-related factors, and develop the empirical antimicrobial treatment-decision algorithm. All adult, positive blood cultures at the emergency room and outpatient clinics were evaluated from 08/2021 to 04/2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were previously sensitive. A total of 1151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Non-susceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed using the independent risk factors for AMR-BSI: presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63), prior antimicrobial exposure within 90 days (aOR 1.94), and urinary source (aOR 1.79). The positive and negative predictive values were 53.3% and 83.2%, respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39), solid malignancy (aHR 2.61), and urinary source (aHR 0.30). In conclusion, one-fourth of community-onset BSI were antimicrobial-resistant, and one-third of Enterobacteriaceae were non-susceptible to ceftriaxone. Treatment-decision algorithms may reduce overly broad antimicrobial treatment.

Changing epidemiology, microbiology and mortality of bloodstream infections in patients with haematological malignancies before and during SARS-CoV-2 pandemic: a retrospective cohort study

ObjectiveThis study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.DesignRetrospective cohort study between 2018 and 2021.SettingThe largest...

Infections in children following chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is transforming care for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). There are limited pediatric-specific data concerning the infection risks associated with CD19 CAR-T therapy and the adequacy of current antimicrobial prophylaxis guidelines for these patients. We describe the antimicrobial prophylaxis used and the types of infectious occurring in the first 100 days following CAR-T therapy for relapsed or refractory B-cell ALL in children and adolescents (≤18 years) at our centre. Twenty-seven patients received their first CAR-T infusion (CTI) during the study period. Almost all patients (96%) had a comprehensive Infectious Diseases review prior to CTI, which informed a personalised prophylaxis or fever/sepsis plan in six (22%). Overall, six (22%) patients had one or more infections during the study period including five (19%, 0.9 per 100 days-at-risk) from days 0-30 and three (n = 20, 15%, 0.6 per 100 days-at-risk) from days 31-100. Bacterial blood stream infections were the most common type of infection encountered during both time periods, and one patient had probable pulmonary aspergillosis. There were no infection-related deaths. Our study contributes important information on the spectrum of infections encountered in pediatric patients with B-ALL post CAR-T therapy. Overall, the burden of infectious complications post CAR-T therapy in our cohort is lower than previously reported in the literature. Results suggest that our prophylaxis recommendations are effective in this population.