Bacterial Bloodstream Infections Research Articles

Recurrent Group B Streptococcus Septicemia Secondary to Portal Hypertensive Colopathy

Background Group B streptococcal infections (GBSs) in nonpregnant adults have become an increasingly recognized entity. Bacteremia without focus has consistently been demonstrated as the second leading cause of infection. Recurrent bacteremia, however, remains a significantly rarer phenomenon, and underlying mechanisms and risk factors are poorly elucidated in the literature. Case Report We report the first case of 3 independent episodes Streptococcus agalactiae bacteremia without focus, in 56-year-old woman with Child-Pugh B cirrhosis and the uncommon finding of portal hypertensive colopathy. Results We propose bowel hemorrhage secondary to portal hypertensive colopathy, facilitated recurrent bacterial translocation and blood stream infection in this immunocompromised host, presenting as recurrent bacteremia without focus. We discuss the disease epidemiology of GBS infections, antibiotic sensitivity, and risk factors for infection relating to this theory in a literature review. Conclusions Portal hypertensive colopathy in liver cirrhosis may contribute to underlying risk for recurrent GBS bacteremia without focus that necessitates prolonged penicillin class antibiotic therapy.

Machine-learning based prediction of prognostic risk factors in patients with invasive candidiasis infection and bacterial bloodstream infection: a singled centered retrospective study

BackgroundInvasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited.MethodsWe included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3).ResultsOf the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25–74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level.ConclusionOur results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level.

Use of Rapid Molecular Polymerase Chain Reaction in Early Detection of Bacteremia in Neonates Prior to Blood Culture Positivity: A Pilot Study.

There has been national strive to decrease the time needed to identify microorganisms in blood culture samples to reduce antibiotic use. This study evaluated rapid molecular polymerase chain reaction (PCR) use in identifying microorganisms in negative culture bottles from neonates with suspected bacterial blood stream infection at 20 to 24 hours of incubation. All blood specimens from neonates with suspected blood stream infection were included. Specimens were incubated using a standard blood culturing instrument that would flag positive if bacterial growth was detected. If the specimen was flagged positive at <20 hours, it was tested by PCR and plated for identification as per standard protocol. In our design, if specimen was not flagged at 20 hours of incubation, the bottle was sterilely accessed and a sample was obtained for PCR testing. The bottle would be returned for incubation for 120 hours or until flagged positive. A total of 192 blood specimens were included. Four specimens flagged positive at <20 hours and were all found to be positive by PCR. All other samples did not flag positive by 20 hours of incubation and were tested by PCR between 20 and 24 hours. One sample tested positive via PCR at 21.6 hours then flagged positive on the culturing instrument at 23.5 hours. All other specimens were negative by PCR and remained culture negative at 120 hours. The positive and negative predictive value of PCR verified by blood culture were both equal to 1.0. Using rapid molecular PCR on blood culture specimens at 20 to 24 hours of incubation provides 100% true negative results possibly allowing providers to discontinue antibiotics at 24 hours. · Antibiotic overuse leads to adverse neonatal outcomes.. · Molecular PCR may have true negative results.. · Larger study is needed to discontinue antibiotics earlier..

Systemic infections associated with tattoos or permanent makeup: A systematic review

IntroductionThe aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture. MethodsA literature search was performed in PubMed database (2009–2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews. ResultsWe identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis. ConclusionsBacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

Rare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogens may translocate from the gut microbiome into the bloodstream to cause infections, the mechanisms by which HCT patients acquire pathogens in their microbiome have not yet been described. Here, we use linked-read and short-read metagenomic sequencing to analyze 401 stool samples collected from 149 adults undergoing HCT and hospitalized in the same unit over three years, many of whom were roommates. We use metagenomic assembly and strain-specific comparison methods to search for high-identity bacterial strains, which may indicate transmission between the gut microbiomes of patients. Overall, the microbiomes of patients who share time and space in the hospital do not converge in taxonomic composition. However, we do observe six pairs of patients who harbor identical or nearly identical strains of the pathogen Enterococcus faecium, or the gut commensals Akkermansia muciniphila and Hungatella hathewayi. These shared strains may result from direct transmission between patients who shared a room and bathroom, acquisition from a common hospital source, or transmission from an unsampled intermediate. We also identify multiple patients with identical strains of species commonly found in commercial probiotics, including Lactobacillus rhamnosus and Streptococcus thermophilus. In summary, our findings indicate that sharing of identical pathogens between the gut microbiomes of multiple patients is a rare phenomenon. Furthermore, the observed potential transmission of commensal, immunomodulatory microbes suggests that exposure to other humans may contribute to microbiome reassembly post-HCT.

Bacterial Bloodstream Infection in Renal Transplant Recipients: 15 years experience in an university hospital

Bacterial Bloodstream Infection in Renal Transplant Recipients: 15 years experience in an university hospital

Comparison of serum cytokines for bacteremia and fungemia in rat bloodstream infection model

Objective We aim to measure the serum levels of cytokines/chemokines in cases of candidemia and bacteremia using mouse model. Methods and Materials: Mice models of bloodstream infection (BSI) with Staphylococcus aureus (Sa), Enterococcus faecalis (Ef), Escherichia coli (Ec), Klebsiella pneumonia (Kp), Candida albicans (Ca) and Candida parapsilosis (Cp) were established. Cytokines and chemokines including TNF-α, IL-1β, IL-10, IL-17, MIP-1β, MIP-2 and G-CSF in serum were detected by Luminex xMAP assay and were compared among different groups at different time points. Results: TNF-α, IL-1β and G-CSF first increased and then decreased after infection in all infection groups, while IL-10 decreased to the minimum levels 12h after injection and then gradually increased. As for IL-17, MIP-1β and MIP-2, they increased more rapidly than the other cytokines and then also decreased. The maximum levels of TNF-α, IL-1β, IL-17 MIP-1β and MIP-2 were all higher in GN group, when compared with GP groups and fungemia groups. Peak level of G-CSF in GP groups was higher than the other two groups, while IL-10 was the highest in fungemia groups. Conclusion: Our study indicates that variation trend of serum cytokines and chemokines were different in bacterial or fungal BSI models.

Prevalence of Multidrug Resistant Bloodstream Bacterial Infections among Hospitalized COVID-19 Egyptian Patients and Evaluation of Predictors for Case Severity

Prevalence of Multidrug Resistant Bloodstream Bacterial Infections among Hospitalized COVID-19 Egyptian Patients and Evaluation of Predictors for Case Severity

Patients' Experiences With Staphylococcus aureus and Gram-Negative Bacterial Bloodstream Infections: Results From Cognitive Interviews to Inform Assessment of Health-Related Quality of Life.

BackgroundWe previously conducted a concept elicitation study on the impact of Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) on health-related quality of life (HRQoL) from the patient’s perspective and found significant impacts on HRQoL, particularly in the physical and functional domains. Using this information and following guidance on the development of patient-reported outcome (PRO) measures, we determined which combination of measures and items (ie, specific questions) would be most appropriate in a survey assessing HRQoL in bloodstream infections.MethodsWe selected a variety of measures/items from the Patient-Reported Outcomes Measurement Information System (PROMIS) representing different domains. We purposefully sampled patients ~6–12 weeks post-SAB/GNB and conducted 2 rounds of cognitive interviews to refine the survey by exploring patients’ understanding of items and answer selection as well as relevance for capturing HRQoL.ResultsWe interviewed 17 SAB/GNB patients. Based on the first round of cognitive interviews (n = 10), we revised the survey. After round 2 of cognitive interviewing (n = 7), we finalized the survey to include 10 different PROMIS short forms/measures of the most salient HRQoL domains and 2 adapted questions (41 items total) that were found to adequately capture HRQoL.ConclusionsWe developed a survey from well-established PRO measures that captures what matters most to SAB/GNB patients as they recover. This survey, uniquely tailored to bloodstream infections, can be used to assess these meaningful, important HRQoL outcomes in clinical trials and in patient care. Engaging patients is crucial to developing treatments for bloodstream infections.

222. Clinical and Microbiological Characteristics of Common Bacterial Bloodstream Infections in the US Military Health System

BackgroundBloodstream infections (BSI) are associated with inpatient morbidity in the United States. We sought to characterize the epidemiology of common bacterial BSIs in individuals receiving care within the US Military Health System (MHS), which actively prospectively captures clinical and microbiological data from both retired and active-duty US Uniformed Service members and their beneficiaries.MethodsWe performed a retrospective cohort study analyzing MHS patients with blood cultures positive for all bacterial pathogens, between January 2010 and December 2019. Microbiological data captured by the Navy and Marine Corpse Public Health Center, excluding cultures isolating contaminants, were retrospectively collated with clinical and demographic data from the MHS Data Repository. ResultsThe most frequent nine bacterial pathogens, as well as Acinetobacter spp. represented 17,206 episodes of BSI from 14,531 individuals. The cohort was predominantly male (59.4%) and ≥65 years old (48.7%). Most individuals were retired (N=5,249) or active duty (N=1,418) service members and their dependents (N=5,236). Median Updated Charlson Comorbidity Index Score was 2. Chronic pulmonary disease was the most frequent comorbid condition. Hospital admission was associated with 13,733 (79.8%) BSI episodes, including 5,870 admissions to the ICU. Overall, inpatient mortality was 8.3%. E. coli (29.7%, N= 5,114) was isolated with the highest frequency, followed by S. aureus (22.4%, N=3,853). Further, 9.5% of E. coli and 36.9% of S. aureus isolates were resistant to ceftriaxone and oxacillin, respectively. Beta-hemolytic streptococci represented the highest percentage (6.3%) of recurrent BSI episodes occurring at least 14 days post-initial BSI. Males or Native American race were most commonly infected with S. aureus. E. coli BSI was most common in all other demographic categories. Frequency of Bacterial Blood Stream Infections in the US Military Health System The most frequent nine bacterial pathogens, as well as Acinetobacter spp. in the US Military Health System.ConclusionWe assessed the epidemiologic features of all individuals with BSI receiving care in the MHS over a 10-year period. We noted demographic differences in the occurrence of microbiological causes of BSI including S. aureus. Further assessments are underway into BSI-related risk factors for occurrence, antimicrobial resistance and mortality, after controlling for comorbidities and disease severity.Disclosures All Authors: No reported disclosures

Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplantation Patients

Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but data supporting this practice are inconsistent. In addition to concern for lack of benefit, there are also concerns that this practice could increase the rates of Clostridioidesdifficile (C diff) infections, the incidence of multidrug-resistant organisms (MDRO) or lead to increased incidence of acute graft-versus-host disease (aGVHD) by disrupting the gut microbiome. This study aimed to assess the safety and efficacy of levofloxacin as bacterial prophylaxis in pediatric and young adult patients undergoing allogeneic or autologous HSCT at a single pediatric center. We conducted a retrospective chart review evaluating patients age ≥6 months who underwent HSCT at our center between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin prophylaxis, whereas those who underwent transplantation after April 2018 did receive levofloxacin prophylaxis. Each transplantation was included as a separate episode if the patient underwent more than 1 transplantation during the inclusion time. The primary outcome of this study was the proportion of patients who experienced at least 1 bacterial bloodstream infection (BSI) in the first 100 days post-transplantation. Secondary outcomes included the number of non-levofloxacin antibiotic days post-transplantation, the incidence of aGVHD, the occurrence of C diff infections, and development of MDRO. A total of 370 HSCT recipients with a median age of 6.7 years (range, 0.5 to 39 years) were included in this study. Seventy-two patients had undergone more than 1 transplantation, and thus we had 443 transplantations to observe. Of these, 216 did not include levofloxacin prophylaxis and 227 included levofloxacin prophylaxis. There were no differences in baseline characteristics between the 2 groups except for age; patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs 9.6 years; P=.05). There were no between-group differences in rates of death at 100 days, antibiotic use, fungal infections, or MDRO infections. Patients in the non-prophylaxis group developed more bacterial BSI in the first 100 days post-HSCT (27% versus 17%; P=.004) and more C diff infections (20% versus 9%; P=.003) than patients who received levofloxacin prophylaxis. In addition, more aGVHD was seen in the patients without levofloxacin prophylaxis (P=.014). Levofloxacin prophylaxis given from day -2 of HSCT through engraftment was significantly associated with decreased bacterial BSI in the first 100 days post-transplantation and was not associated with increased risks of C diff, aGVHD, or MDRO. Our study supports the use of levofloxacin prophylaxis in the peritransplantation period. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

59. Risk Factors for Recurrent Gram-Negative Bacterial Bloodstream Infections

BackgroundGram-negative bacteria bloodstream infections (GNB-BSI) are a significant cause of morbidity and mortality. Recurrent GNB-BSI is an incompletely understood phenomenon. In this study we identify risk factors for recurrent GNB-BSI.MethodsPatients with GNB-BSI have been prospectively enrolled into the Bloodstream Infection Biorepository (BSIB) since 2002. From the BSIB, patients with >1 episode of GNB-BSI with the same bacterial species were identified. Chi-Square, Fisher Exact, and a multivariate linear regression models were used to identify clinical risk factors for recurrent GNB-BSI. Paired isolate samples from the initial and the recurrent episode of GNB-BSI in same patient underwent Pulsed Field Gel Electrophoresis (PFGE) to differentiate Relapse (paired isolates identical) from Reinfection (paired isolates different).ResultsAmong the 1,423 unique patients with GNB-BSI enrolled from 2002- 2015, 60 (4.2%) experienced recurrent GNB-BSI with the same bacterial species. Median time to recurrent GNB-BSI was 133 d (IQR: 40-284.75 days). Causes of recurrent-GNB-BSI included Escherichia coli (38%), Klebsiella species (30%), Pseudomonas aeruginosa (12%), and Serratia marcescens (5%) and did not differ from causes of non-recurrent GNB-BSI (Figure 1). Risk factors for recurrent GNB-BSI included Black race (OR: 2.45 [CI: 1.43-4.20]), implanted cardiac device (OR: 2.39 [CI: 1.00-5.07]), and admission to surgical service (OR: 2.16 [CI 1.24-3.75]). Forty-eight isolate-pairs from 43 patients with recurrent GNB-BSI underwent PFGE, relapse occurred in 31 (65%) and reinfection occurred in 17 (35%). Risk factors for GNB-BSI relapse included cardiac device (OR: 3.7 [CI: 1.7-8.3]), and admission to surgical service (OR: 3.7 [CI:1.3-9.4]).Figure 1: Species Breakdown Proportional comparison of the Gram-negative bacterial species identified in patients with recurrent and non-recurrent bloodstream infections.ConclusionRecurrent GNB-BSI is an uncommon complication of GNB-BSI. Recurrent GNB-BSI is most often driven by relapse, as opposed to reinfection, and is associated with associated with black race, implanted cardiac devices and admission to surgical service.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)

Initial Specimen Diversion Device® reduces blood culture contamination and vancomycin use in academic medical centre

In suspected bloodstream infections, accurate blood culture results are critical to timely diagnoses and appropriate antibiotic administration. An Initial Specimen Diversion Device®, Steripath® (Magnolia Medical Technologies, Seattle, WA, USA) was evaluated for efficacy in reducing blood culture contamination at Brooke Army Medical Center (6.8% six-month contamination rate prior to intervention) in a six-month quality improvement project. Blood cultures in the emergency department were collected using either Steripath or the standard method. Blood samples of 20 mL were cultured into an aerobic and anaerobic medium and incubated for five days using an automated microbial detection system immediately after collection. Positive bottles were Gram-stained and plated. Rapid molecular polymerase chain reaction identification was performed on all first positive bottles within a blood culture set for each admission or ED visit. Speciation was deduced during antimicrobial sensitivity testing using the Vitek-2 instrument. Seven out of 1016 (0.69%) contamination events occurred when using Steripath vs 53 out of 800 (6.6%) contamination events when using the standard method. Steripath use was associated with a 90% lower incidence of blood culture contamination vs the standard method. Post study, Steripath use was implemented as standard practice hospital-wide, and a retrospective data analysis attributed a 31.4% decrease in vancomycin days of therapy to Steripath adoption. Using Steripath significantly decreased blood culture contamination events for bacterial bloodstream infections compared to the standard method. Subsequent adoption of Steripath reduced overall vancomycin usage. With widescale implementation Steripath could bolster antibiotic stewardship, mitigating antibiotic resistance caused by unnecessary antibacterial treatments.

Bacterial Prophylaxis in Patients with Acute Gvhd; Who Is at Risk for Bloodstream Infections?

Consensus on the need for antibacterial prophylaxis in patients with acute graft-vs.-host disease (AGVHD) has not been established with practices varying across centers. The aim of this study was to determine the risk for bacterial bloodstream infections (BSI) from neutrophil engraftment through day 100 post-hematopoietic cell transplant (HCT) in patients with AGVHD and whether organ involvement and severity impact this risk.Methods: The cause-specific hazards for developing BSI after-engraftment by day 100 was compared between patients with and without grade II-IV AGVHD by treating AGVHD as a time-dependent variable.Results: A total of 4064 adult patients who underwent a matched related, matched unrelated, or mismatched unrelated T-cell replete, marrow or blood HCT for AML, ALL, or MDS from 2008-2012 within the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients, 62% of which had lower GI involvement and 70% had skin involvement. In multivariate analysis (MVA), the hazard ratio for BSI was 1.83 (95% CI: 1.53-2.18; p<0.0001) in those with grade II-IV AGVHD vs. those with grade 0/I. Patients with grade III/IV AGVHD had the highest risk for BSI (HR 2.45; 95% CI 1.99-3.0; p <0.0001) with a borderline risk for those with grade II (HR 1.35; 95% CI 1.03-1.77; p=0.0275). Patients with lower GI involvement had higher risk when compared to those with grade II-IV AGVHD without GI involvement (HR 1.54; 95% CI 1.17-2.02; p=0.0019) with risk being incrementally higher with each lower GI stage (1-4). Patients with isolated stage 3 skin AGVHD (n=214) did not have significantly higher risk for BSI (HR 1.25; 95% CI 0.82-1.91; p= 0.3); however, those with isolated stage 4 (n=27) had higher risk (HR 3.30; 95% CI 1.74-6.27; p=0.0003) when compared to those with grade 0/I AGVHD. In MVA, patients who developed a BSI between engraftment and day 100 post-transplant had worse survival (HR 1.64, 95% CI 1.43-1.87; p <0.001) and higher non-relapse mortality (NRM), HR 2.22; 95% CI 1.91-2.59; p <0.001). When evaluating type of infections: Gram negative bacteremia was seen in a higher proportion of patients (7%) with lower GI involvement vs. 4% in those without lower GI involvement and 4% in those with grade 0/1 AGVHD (p <0.01). Staphylococcus aureus bacteremia was seen in a higher proportion of patients with grade 2-4 AGVHD with skin involvement (4%) vs. 2% in those without skin involvement and 1% in those with grade 0/1 AGVHD (p <0.01).Conclusions: Patients with grade II-IV AGVHD are at higher risk for BSI compared to patients with grade I AGVHD or no AGVHD. Those with lower GI involvement or with stage 4 skin AGVHD are at highest risk. The development of BSI is associated with worse survival and higher NRM. Strategies for the lowering the risk for BSI in high risk patients are needed. [Display omitted] DisclosuresGulbis: EUSA Pharma: Other: Advisory board participation. Kitko: Vanderbilt University Medical Center: Current Employment; Co-investigator on two NIH grants as part of the cGVHD consortium: Research Funding; Horizon: Membership on an entity's Board of Directors or advisory committees; PER: Other: PER - CME educational talks about GVHD. MacMillan: Equilium: Other: DSMB member; Incyte: Consultancy; Jazz Pharmaceuticals: Consultancy. Pidala: CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Regeneron: Consultancy; Pharmacyclics: Other: Clinical trial support, Research Funding; Incyte: Consultancy; Takeda: Other: Clinical trail support; Novartis: Other: Clinical trail support; BMS: Other: Clinical trial support, Research Funding; Johnson and Johnson: Other; Jannssen: Other: Clinical trial support; BMS: Other; AbbVie: Other. Riches: Jazz Pharmaceuticals: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees; ATARA Biotherapeutics: Other: Payment. Arora: Kadmom: Research Funding; Syndax: Research Funding; Pharmacyclics: Research Funding.

Clinical Characteristics of Severe Acute Chest Syndrome in Children with Sickle Cell Disease

Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD.Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test.Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort.Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. DisclosuresTubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.

G-CSF as a potential early biomarker for diagnosis of bloodstream infection.

BackgroundCytokines play an important role in bacterial infection, and thus, we aim to find out cytokines that may be diagnostically significant in early stage of bacterial bloodstream infection.MethodsMice models infected with Staphylococcus aureus and Klebsiella pneumoniae were established. Then dynamic changes of nine serum cytokines were monitored within 48 hours after the infection. Cytokines with significant differences between the infected groups and control group were further analyzed. Clinical samples of patients who were suspected of bloodstream infection were collected. Then the diagnostic efficiency of screened cytokines was determined with receiver operating characteristic curve analysis.ResultsAs for mice models infected by Staphylococcus aureus and Klebsiella pneumoniae, six cytokines including IL‐1β, IL‐6, IL‐12p70, G‐CSF, IFN‐γ, and TNF‐α were significantly different (P < .05) between two bacterial infected groups. As for clinical samples, three cytokines including IL‐6, IL‐12p70, and G‐CSF showed significant differences between infection group (Staphylococcus aureus and Klebsiella pneumonia group) and negative control group. With the area under curve of 0.7350 and 0.6431 for G‐CSF and IL‐6, respectively, these two cytokines were significantly different between Staphylococcus aureus and Klebsiella pneumoniae infection groups. Combination of G‐CSF and IL‐6 could improve the AUC to 0.8136.ConclusionsG‐CSF cannot only identify bacterial bloodstream infection, but can also distinguish the infection of Staphylococcus aureus from Klebsiella pneumoniae. Further investigation should be performed concerning the diagnostic efficiency of G‐CSF in diagnosing different types of bacterial bloodstream infection.

Bloodstream bacterial infections in thalassemic pediatric and adolescent patients after hematopoietic stem cell transplantation.

Thalassemic patients usually require regular blood transfusions; however, HSCT can provide a cure. Incidence of IBI in pediatric patients post-HSCT is still scant. This study aimed to explore whether thalassemic patients had a different incidence of post-HSCT IBI compared with patients with other underlying diseases. Factors associated with IBI in the pediatric population undergoing HSCT were also investigated. In this retrospective cohort study, clinical data of pediatric patients who underwent HSCT during the period from 2011 to 2016 were reviewed and analyzed. The primary outcome was incidence of IBI within 1-year post-HSCT. Of 123 patients, 53 were thalassemic. IBI was diagnosed in 23 patients within 1year after HSCT (incidence: 19.5 episodes/1000patients/month). The IBI incidence was lower in thalassemic patients than in patients with other underlying diseases (6.9 vs. 31.6 episodes/1000patients/month). Having thalassemia as an underlying disease was the only factor associated with lower IBI in pediatric post-HSCT patients (hazard ratio: 0.245; 95% confidence interval, 0.080-0.748). In post-HSCT thalassemic patients, IBI mostly occurred within 100days after HSCT, and most of these cases had catheter-related blood stream infection. The risk of IBI tended higher for haploidentical HSCT, but this difference was not statistically significantly different. The IBI incidence after HSCT was lower in thalassemic patients than in those with other underlying diseases. Catheter-related blood stream infection was the major IBI in these patients. IBI was not a major complication in thalassemic pediatric patients undergoing HSCT.

Serum Cytokine Profile in Patients with Candidemia versus Bacteremia.

Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1β, IL-6, IL-17A, IL-10, IFN-γ, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections.

Major bacterial isolate and antibiotic resistance from routine clinical samples in Southern Ethiopia

Currently, antibiotic-resistant bacterial infections are a challenge for the health care system. Although physicians demand timely drug resistance data to guide empirical treatment, local data is rather scarce. Hence, this study performed a retrospective analysis of microbiological findings at the Hawassa public hospital. Secondary data were retrieved to assess the prevalence and level of drug resistance for the most common bacterial isolates from clinical samples processed at Hawassa University Comprehensive Specialized Hospital. Out of 1085 clinical samples processed in the microbiology laboratory, the prevalence of bacterial infection was 32.6%. Bacterial bloodstream infection was higher in children than in adults (OR, 4; 95% CI 1.8–14.6; p = 0.005). E. coli and K. pneumoniae were the commonest bacterial isolate both in children (36.8%, 26.3%) and in adults (33.3%, 26.7%) from the urine sample while, the leading bacteria identified from the CSF sample was P. aeruginosa, 37% in children and 43% in adult. In this study, all identified bacterial isolates were multi-drug resistant (MDR) ranging from 50 to 91%. The highest proportion of MDR was S. aureus 91.1 followed by K. pneumoniae 87.6%. Since the nationwide investigation of bacterial isolate, and drug resistance is rare in Ethiopia, a report from such type of local surveillance is highly useful to guide empirical therapy by providing awareness on the level resistance of isolates.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years

ObjectivesBacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. MethodsThis was a retrospective chart review looking at bacterial BSI episodes between 2007–2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. ResultsAmong 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/μL (OR = 0.12, 95% CI 0.03–0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. ConclusionThe persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.