Mucosal Barrier Injury Laboratory-confirmed Bloodstream Infection Research Articles

P-890. Risk Factors Associated with Carbapenem-Resistant Enterobacteria Bacteremia and Mortality in Patients with Acute Leukemia

Abstract Background The inclusion of highly cytotoxic drugs for the treatment of acute leukemia (AL) in the last decade has exposed patients to more extended periods of severe neutropenia. The study aims to describe the prevalence and risk factors for blood-stream infection (BSI) due to carbapenem-resistant enterobacteria (CRE) in patients with AL receiving chemotherapy.Table 1.Independent risk factors for blood-stream infection due to carbapenem-resistant enterobacteria FLAG-IDA chemotherapy regimen had an OR 28.8 (CI 2.9-286.68. p=0.004) for CRE-BSI Methods The study was performed at a referral center for adult patients with cancer in Mexico City. From January 2021 to December 2022, all patients with AL treated from first to fourth line chemotherapy were included. CRE and non-CRE BSI were compared for categorical variables with Pearson's chi-square. A bivariate logistic regression analysis was performed to identify risk factors associated with mortality and isolation of CRE.Table 2.Independent risk factors for mortalityPatients with AML had an OR 7 (CI 1.26-39.23 p=0.026), isolation of CRE OR 6.8 (CI 1.17-0.03 p=0.03) and being diagnosed with invasive fungal infection (IFI) OR 5.2 (CI 1.29-26.66 p=0.02) for mortality Results One hundred ten patients were included: 62 (56.3%) with acute lymphoblastic leukemia (ALL) and 48 (43.6%) with acute myeloid leukemia (AML). 119 BSI were confirmed, 41 (34%) blood isolates were antimicrobial resistant, 23 (56.1%) had extended-spectrum beta-lactamases (ESBL), and 16 (39%) had CRE. BSIs were classified as 70 (58.8%) Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection (MBI-LCBI), 24 (20.1%) secondary, 23 (19.3%) catheter-related and 2 (1.6%) primary. Of the 23 (56.1%) isolates with ESBL and 16 (39%) CRE, all were classified as MBI-LCBI, as were two (4.9%) methicillin-resistant S. aureus. Overall, 30-day mortality was 9.2%, and at 24 weeks, 16.8%. In the bivariate analysis, receiving a FLAG-IDA had an OR 28.8 (CI 2.9-286.68. p=0.004) for CRE-BSI (Table 1). For mortality, having AML had an OR 7 (CI 1.26-39.23 p=0.026), CRE BSI isolates OR 6.8 (CI 1.17-0.03 p=0.03), and being diagnosed with invasive fungal infection (IFI) OR 5.2 (CI 1.29-26.66 p=0.02) (Table 2). Kaplan-Meier model comparing patients with and without CRE-BSI showed a mean survival of 17.8 months in CRE-BSI vs. 23.4 months without CRE-BSI, although non statistical significance (Figure 1).Figure 1.Kaplan-Meier survival analysisKaplan-Meier model comparing patients with and without CRE-BSI showed a mean survival of 17.8 months in CRE-BSI vs. 23.4 months without CRE-BSI, although without statistical significance Conclusion In this cohort, overall mortality was associated with AML, having CRE isolated in blood, and having been diagnosed with IFI. Having a CRE-BSI was associated with receiving FLAG-IDA. This highly myelosuppressive chemotherapy regime has become a niche for antimicrobial resistance development in our institution. Disclosures All Authors: No reported disclosures

Bloodstream infections in a Brazilian Pediatric Tertiary Oncology Hospital: 30-month analysis regarding the classification of the infection, distribution of microorganisms and their resistance profile

Abstract Background Infections are a major cause of morbidity and mortality in pediatric oncology patients during their treatment. Bloodstream infections are the main site of infection in these patients. Bacteremia in these patients can be secondary to a primary infectious focus, result from central line associated bloodstream infections (CLABSIs) or mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI). Methods Descriptive study of bloodstream infections in pediatric patients undergoing oncological treatment and hematopoietic stem cell transplantation in a tertiary pediatric oncology hospital in Brazil from January 1st, 2021 to June 30th, 2023. Infections were classified according to the Centers for Disease Control and Prevention/ National Healthcare Safety Network (CDC/NHSN) criteria into CLABSIs, MBI-LCBIs and secondary bloodstream infections. Among the bloodstream infections that met CDC/NHSN criteria for CLABSI, were analyzed separately those who also met the criteria of catheter-related bloodstream infection (CRBSI) according to Infectious Diseases Society of America (IDSA). Results During this period were diagnosed 335 episodes of bloodstream infection (123 episodes in 2021, 150 in 2022 and 62 episodes in the first 6 months of 2023). There were 378 microorganisms isolated. These infections were classified into: 35% CLABSIs, 27% MBI-LCBIs, 23% CRBSIs, and 15% secondary bloodstream infections. Among the CLABSIs, the most common microorganisms were non-fermenting gram negative bacilli (NFGNB) 38%, enterobacteriaceae 35% and coagulase-negative staphylococcus (CoNS) 11%. Between CRBSIs, there were 31% enterobacteriaceae, 22% CoNS and 19% NFGNB. Among the MBI-LCBIs there were 66% enterobacteriaceae and 23% group viridans streptococci (VGS). Streptococcus pneumoniae (33%) was the most common microorganism in secondary infections followed by Staphylococcus aureus (17%). Assessing all infections together, the main enterobacteriaceae were Klebsiella spp. (40%) and only 50% of them were sensitive to cefepime while 10% were carbapenems resistant. Among NFGNB, 13% of Pseudomonas spp. and 5% of Acinetobacter spp. were carbapenems resistant. Between the gram-positive bacteria, 77% of the S. aureus were methicillin sensitive, the same percentage of the VGS were sensitive to cefepime. Conclusion Among bloodstream infections, there were a predominance of CLABSI followed by MBI-LCBIs. Antimicrobial resistance between gram-positive bacteria, is of little concern in our institution. In the case of gram-negative bacteria, resistance to cefepime is becoming worrying among enterobacteriaceae.

The applicability of the central line-associated bloodstream infection (CLABSI) criteria for the evaluation of bacteremia episodes in pediatric oncology patients.

The aim of this study was to investigate the applicability of the central line-associated bloodstream infection (CLABSI) criteria of the Centers for Disease Control and Prevention in pediatric oncology patients. Bacteremia episodes from 2020 to 2022 from a prospective cohort of pediatric oncology patients with a central venous catheter were included. Episodes were classified by three medical experts following the CLABSI criteria as either a CLABSI or non-CLABSI (i.e., contamination, other infection source, or mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI)). Subsequently, they were asked if and why they (dis)agreed with this diagnosis following the criteria. The primary outcome was the percentage of episodes where the experts clinically disagreed with the diagnosis given following the CLABSI criteria. Overall, 84 bacteremia episodes in 71 patients were evaluated. Following the CLABSI criteria, 34 (40%) episodes were classified as CLABSIs and 50 (60%) as non-CLABSIs. In 11 (13%) cases the experts clinically disagreed with the diagnosis following the CLABSI criteria. The discrepancy between the CLABSI criteria and clinical diagnosis was significant; McNemar's test p < .01. Disagreement by the experts with the CLABSI criteria mostly occurred when the experts found an MBI-LCBI a more plausible cause of the bacteremia than a CLABSI due to the presence of a gram negative bacteremia (Pseudomonas aeruginosa n = 3) and/or mucositis. A discrepancy between the CLABSI criteria and the evaluation of the experts was observed. Adding Pseudomonas aeruginosa as an MBI pathogen and incorporating the presence of mucositis in the MBI-LCBI criteria, might increase the applicability.

2723. High Mortality and Resistance in Patients with Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBI)

Abstract Background Since its definition, MBI-LCBI is a pathology increasingly studied and frequent, however, with the growing threat of multidrug resistance (MDR), it is very important to have pharmacological resources for the treatment and local epidemiology. The economic constraints that many institutions suffer in lower middle-income countries may result in worse outcomes in MBI-LCBI and carbapenem-resistant Enterobacteriaceae (CRE) patients. In Ecuador, only ceftazidime/avibactam is available for the CRE treatment, and it is not considered in the Ecuadorian National formulary (EFN), that means it is not available in public health institutions. Methods A retrospective study was conducted in two cancer reference hospitals in Ecuador, from January 2019 to December 2021. All patients with MBI-LCBI according to CDC criteria were included. Demographic, diagnostic, and microbiological isolation data were collected. Strains identification and susceptibility were performed on Vitek 2 system and Kirby Bauer, following CLSI 2022 recommendations and cut-off points. The CRE resistance mechanism was confirmed by PCR. Thirty-day episode mortality was assessed, and compared between susceptible and MDR cases. Data are shown with means, and Chi-Square test was used to evaluate differences between mortality. SPSS version 25 was used. Results 148 episodes of MBI-LCBI in cancer patients were detected. Figure 1 shows etiology and susceptibity of strains. Sixty one (41.3%) MBI-LCBI causing microorganisms were MDR; 25 (68.8%) were BLEE/AmpC isolates and 19 (31.1%) were CRE. The mortality rate of MBI-LCBI patients was 48.6% (72). There was no difference between deaths from BLEE/AMPc versus susceptible bacteremia (22,2% vs. 27,6% p=0,44), however, mortality from CRE strains was higher compared to susceptible strains (20,8% vs. 2,6% p=0.001) figure 2. The risk of dying with MBI-LCBI with CRE strains was OR: 4.5 (95% CI;1.3-15; p=0.01). Conclusion There is a high percentage of resistance and mortality in MBI-LCBI, more notorious when the cause is CRE. This alerts us to the need of further research in this pathology and its appropriate treatment. Ecuadorian health authorities should consider review the EFN to include new active drugs for treatment CRE infections. Disclosures All Authors: No reported disclosures

1857. Risk factors for recurrent bacteremia in children undergoing chemotherapy or hematopoietic stem cell transplantation

Abstract Background Sepsis is a complication frequently encountered in children with underlying malignancies, especially due to a majority of patients having indwelling venous catheters. Indications for catheter removal among children with central-line associated blood stream infection (CLABSI) should follow the recommendations for adults, however, difficulties in vascular access often leads to attempting treatment without catheter removal. Therefore, the primary aim of this study was to find risk factors for recurrent sepsis in children undergoing chemotherapy of HSCT and examine whether more aggressive catheter removal after CLABSI in children is necessary. Methods In the Pediatric Bone Marrow Transplant Center of Seoul St. Mary’s Hospital, positive blood cultures were prospectively monitored to control and prevent outbreaks. The date of culture, culture results, symptoms presented, category of blood stream infections (by the CDC/NHSN surveillance definition (2021) of Bloodstream infections), and central-line associated blood stream infection (CLABSI) events were monitored. Results During September 2016 to February 2021, a total 280 cases of laboratory confirmed bloodstream infections (LCBI) or Mucosal Barrier Injury LCBI (MBI-LCBI) were diagnosed in children &amp;lt; 18 years old with underlying malignancies. Of these, 52.9% (n=148) were male, and the mean age was 9.7 (SD±6.1) years old. CLABSI was diagnosed in 51.8% (n=145), and the most common pathogens cultured were S. mitis/oralis (24.0%, n=67), E. coli (15.4%, n=43), and coagulase negative Staphylococci (CNS) (10.4%, n=29). Recurrent sepsis occured in 17.1% (n=48), and 9.6% (n=27) had two indwelling catheters . Multivariable analysis showed that factors associated with recurrent blood stream infections were as follows: duration of indwelling catheter (OR, 1.002; 95% CI, 1.001-1.004; P&amp;lt; 0.001) and no removal of central lines after previous episode (OR, 51.143; 95% CI, 6.6-395.0; P&amp;lt; 0.001). Conclusion Permanent central lines should be removed as soon as possible, and more aggressive approach in permanent catheter removal after LCBSIs in children is necessary to reduce recurrent infections. Disclosures All Authors: No reported disclosures.

Central-line associated bloodstream infections secondary to strict anaerobes: Time for A definition change?

Background: Central-line–associated bloodstream infections (CLABSIs) arise from bacteria migrating from the skin along the catheter, by direct inoculation, or from pathogens that form biofilms on the interior surface of the catheter. However, given the oxygen-poor environments that obligate anaerobes require, these organisms are unlikely to survive long enough on the skin or on the catheter after direct inoculation to be the true cause of a CLABSI. Although some anaerobic CLABSIs may meet the definition for a mucosal-barrier-injury, laboratory-confirmed, bloodstream infection (MBI-LCBI), some may be not. We sought to determine the proportion of CLABSIs attributed to obligate anaerobic bacteria, and we sought to determine the pathophysiologic source of these infections. Methods: We performed a retrospective analysis of prospectively collected CLABSI data at 54 hospitals (academic and community) in the southeastern United States from January 2015 to December 2020. We performed chart reviews on a convenient sample for which medical records were available. We calculated the proportion of CLABSIs due to obligate anaerobes, and we have described a subset of anaerobic CLABSI cases. Results: We identified 60 anaerobic CLABSIs of 2,430 CLABSIs (2.5%). Of the 60 anaerobic CLABSIs, 7 were polymicrobial with nonanaerobic bacteria. The most common species we identified were Bacteroides, Clostridium, and Lactobacillus (Table 1). The proportion of anaerobic CLABSIs per year varied from 1.2% to 3.7% (Fig. 1). Of 60 anaerobic CLABSIs, 29 (48%) occurred in the only quaternary-care academic medical center in the database. In contrast, an average of 0.6 (SD, 0.6) anaerobic CLABSIs occurred in the 53 community hospitals over the 6-year study period. Of these 29 anaerobic CLABSIs, 23 (79%) were clinically consistent with secondary bloodstream infections (BSIs) due to gastrointestinal or genitourinary source, but they lacked appropriate documentation to meet NHSN criteria for secondary BSI or MBI-LCBI based on case reviews by infection prevention physicians. The other 6 anaerobic CLABSIs did not have a clear clinical etiology and did not meet MBI-LCBI criteria. In addition, 27 (93%) of 29 anaerobic CLABSIs occurred in patients who were either solid-organ transplant recipients, were stem-cell transplant recipients, or were receiving chemotherapy. Lastly, 27 (93%) of 29 anaerobic CLABSIs were treated with antibiotics. Conclusions: Anaerobic CLABSIs are uncommon events, but CLABSI may disproportionately affect large, academic hospitals caring for a high proportion of medically complex patients. Additional criteria could be added to the MBI-LCBI to better classify anaerobic BSI.Funding: NoneDisclosures: None

Applying mucosal barrier injury laboratory-confirmed bloodstream infection criteria in patients with solid tumors and hematologic malignancies: A retrospective cohort study looking for the real source of infection.

We evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line-associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.

Evaluation of central line salvage for mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) management practices in patients with hematologic malignancies

Patients with underlying hematologic malignancy (HM) and/or allogeneic hematopoietic stem cell transplant (HCT) recipients are at risk for mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) secondary to bacterial translocation. There is sparse data comparing MBI-LCBI management practices, in particular central venous catheter (CVC) salvage versus removal. We created a 22-item poll of Infectious Disease specialists at major US cancer centers on management controversies. Response rate was 44% (31/70). CVC salvage was a common practice among 87.5%. This was followed by a single center retrospective study (2017–2019) comparing outcomes related to CVC practices. We identified 115 patients, 52% (60/115) admitted for chemotherapy and 33% (38/115) for allogeneic HCT. The majority of patients (78%, 90/115) had their CVC removed. There was no difference in 72 h defervescence, microbiological clearance, in-hospital mortality, and 90-day recurrent infection between CVC salvage versus removal. CVC salvage is a safe approach in certain clinical scenarios.

909. Reassessing Pathogens Eligible for the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN) “Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infection” Criteria

BackgroundNHSN Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infection (MBI-LCBI) includes pathogens likely to cause bloodstream infections (BSI) in some oncology patients. MBI-LCBIs are excluded from central line-associated BSI (CLABSI) reporting to the Centers for Medicare & Medicaid Services. NHSN users have requested other pathogens be added to MBI-LCBI. To make decision, we compared CLABSI pathogen distributions in three NHSN patient location groups.MethodsWe analyzed CLABSI data from hospitals conducting surveillance for ≥ 1 month from January 2014–December 2018 in ≥ 1 MBI high-risk location (leukemia, lymphoma, and adult and pediatric hematopoietic stem cell transplant wards). We compared CLABSI pathogen distributions and rates in MBI high-risk locations to medium-risk (solid tumor, adult and pediatric general hematology-oncology wards) and low-risk locations (adult and pediatric medical, surgical, and medical-surgical wards), and used χ2 tests to compare percentages with statistical significance at P ≤ 0.05.ResultsOverall, 122 hospitals reported 23,578 CLABSIs and 12,961,921 central line (CL)-days (1.81 CLABSIs per 1,000 CL-days) (Table). Percentages of CLABSIs due to three MBI-LCBI pathogens (E. coli, E. faecium, Viridans streptococci) were significantly higher in high- versus low-risk locations, while for other MBI-LCBI pathogens (K. pneumoniae/oxytoca, E. faecalis, Candida spp., Enterobacter spp.) percentages were significantly lower in high-risk locations (Figure). For pathogens not currently in MBI-LCBI, coagulase-negative staphylococci caused similar percentages of CLABSIs across locations, S. aureus caused a significantly higher percentage of CLABSIs in low-risk locations, while PA caused a significantly higher percentage of CLABSIs in high-risk locations. Table CLABSIs attributed to MBI high-risk, medium-risk, and low-risk locations, NHSN, 2014–2018 Figure Percentages of top 10 pathogen-specific CLABSIs in MBI high-risk, medium-risk, and low-risk locations, NHSN, 2014–2018 ConclusionDifferences in percentages of CLABSIs due to selected pathogens between MBI high-risk and low-risk locations are evident in NHSN data. Lower percentages of Klebsiella and Candida spp. in high-risk locations might be partially due to antimicrobial prophylaxis in oncology patients. Although PA caused a significantly higher percentage of CLABSIs in high-risk locations, the absolute difference was modest. Additional analyses are needed.Disclosures All Authors: No reported disclosures

Incidence of Mucosal Barrier Injury Bloodstream Infections Reported to the National Healthcare Safety Network

Background: The NHSN collects data on mucosal barrier injury, laboratory-confirmed, bloodstream infections (MBI-LCBIs) as part of bloodstream infection (BSI) surveillance. Specialty care areas (SCAs), which include oncology patient care locations, tend to report the most MBI-LCBI events compared to other location types. During the update of the NSHN aggregate data and risk models in 2015, MBI-LCBI events were excluded from central-line–associated BSI (CLABSI) model calculations; separate models were generated for MBI-LCBIs, resulting in MBI-specific standardized infection ratios (SIRs). This is the first analysis to describe risk-adjusted incidence of MBI-LCBIs at the national level. Methods: Data were analyzed for MBI-LCBIs attributed to oncology locations conducting BSI surveillance from January 2015 through December 2018. We generated annual national MBI-LCBI SIRs using risk models developed from 2015 data and compared the annual SIRs to the baseline (2015) using a mid-P exact test. To account for the impact of an expansion in the MBI-LCBI organism list in 2017 from 489 organisms (32 genera) to 1,003 organisms (89 genera), we removed the MBI-LCBI events that met the newly added MBI organisms and generated additional MBI SIRs for 2017 and 2018. Results: The annual SIRs remained above 1 since 2015, indicating a greater number of MBI-LCBIs identified than were predicted based on the 2015 national data (Fig. 1). Each year’s SIR was significantly different than the national baseline, and the highest SIR was observed in 2017 (SIR, 1.377). In 2017, 12% of MBI events were attributed to an organism that was added to the MBI organism list, and in 2018 it was 10%. After removal of MBIs attributed to the expanded organisms, the 2017 and 2018 SIRs remained higher than those of previous years (1.241 and 1.232, respectively). Conclusions: The distinction of MBI-LCBIs from all other CLABSIs provides an opportunity to assess the burden of this infection type within specific patient populations. Since 2015, the increase of these events in the oncology population highlights the need for greater attention on prevention strategies pertinent to MBI-LCBI in this vulnerable population.Funding: NoneDisclosures: None

Surveillance of catheter-related bloodstream infections in haemato-oncology patients: comparison of two definitions

In the Netherlands, the PREZIES surveillance is used for registration and surveillance of central venous catheter (CVC) -related bloodstream infections (CRBSI). We investigated how this Dutch definition correlated with internationally used definitions for CRBSI, central line-associated bloodstream infections (CLABSI) and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI). We determined that the Dutch PREZIES definition of CRBSI is appropriate for surveillance control of CVC care bundle use in haemato-oncology patients managed with multi-lumen CVCs.

Blood stream infections in hematopoietic stem cell transplant patients: A 2-year study from India

Background: Hematopoietic stem cell transplant (HSCT) recipients are particularly prone to bloodstream infections (BSIs). This has been attributed to neutropenia and immune-suppression. Regardless of the improvements made in the management perspective, infection still plays a major role in morbidity and mortality in these patients. It has been related to the rise of multidrug-resistant organisms. Aim: The aim of this study was to determine the pattern of BSIs and the burden of antibiotic resistance in HSCT patients. Materials and Methods: We conducted this retrospective study for 2 years in 438 transplant events among 429 HSCT recipients who developed febrile neutropenia. Paired blood culture samples were collected on the onset of fever. Carbapenem-resistant Enterobacteriaceae (CRE) carriage rate was also determined in 127 patients. Results: BSIs were detected in 131 transplant events, which were classified as mucosal barrier injury laboratory-confirmed BSIs in 61, central line-associated, and other primary BSIs among 35 each. A diverse variety of 145 isolated organisms included Gram-negative and Gram-positive bacteria with 4 Candida species. All the Gram-negative isolates were susceptible to colistin, while 68.83% of CRE was detected. CRE carriage rate was observed in 37.80% of 127 individuals. Vancomycin resistance was noticed in 40% Enterococcus species. The overall mortality rate was 20.05%. Conclusions: Screening for CRE carriage in these patients could help in timely initiation of empirical colistin therapy. However, local epidemiology plays an important role in deciding the empirical antibiotic therapy.

Daily Chlorhexidine Gluconate Bathing Reduces the Rate of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Stem Cell Transplantation

Introduction: While hematopoietic stem cell transplantation (HSCT) has great therapeutic potential, intensive conditioning regimens and variability in time to stem cell engraftment result in a period of pancytopenia and immunosuppression in which patients are vulnerable to infection. Bloodstream infections (BSIs) occur in 20-45% of inpatient autologous and allogeneic transplant patients, leading to prolonged hospitalization and increased mortality. One method of infection prevention is daily application of the antiseptic chlorhexidine gluconate (CHG). Daily CHG bathing, either with a CHG wash or with application of CHG-impregnated cloths, has been shown to reduce the incidence of all-cause hospital-acquired BSIs in critically ill patients, such as those in the ICU, though very few studies include HSCT patients. Methods: We conducted an observational cohort study to assess the impact of daily CHG bathing on the rate of BSIs among adults undergoing inpatient HSCT at the Duke University Medical Center. Patients were included if they were admitted for pre-transplant conditioning and inpatient monitoring for allogeneic or autologous HSCT from January 2016 through December 2018. CHG bathing was instituted in January 2017 for all patients admitted to the inpatient HSCT unit using 2% CHG-impregnated cloths (SAGE™), providing one year of data with no CHG bathing and two years of data with bathing. Patients were tracked from admission until unit discharge, transfer, or first infection. Laboratory-confirmed bloodstream infections (LCBI), central-line associated bloodstream infections (CLABSI), and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI) were determined per CDC/NHSN definitions. An additional variable of "clinically-significant infection" was recorded; this included both laboratory-confirmed BSIs and infections deemed significant by the treatment team but that did not meet CDC/NHSN criteria. For example, patients that were febrile, hypotensive, and treated with antibiotics, but with only one positive culture of a common commensal were deemed to have a clinically-significant BSI. Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: High (&gt;75%), Medium (50-75%), Low (1-49%), and None (0%). Baseline characteristics and clinical outcomes between groups were compared via ANOVA, Chi-squared test, or Cochran-Armitage two-sided trend test. Multivariate analysis using the Fine-Grey subdistribution hazard model was conducted to compare time to all infection variables, accounting for the effects of CHG usage, antibiotic prophylaxis regimen, and type of transplant. Results: We evaluated 192 patients hospitalized for HSCT, including 118 (62%) allogeneic transplants and 74 (38%) autologous transplants. Of these, 25 (13%) had high CHG usage, 33 (17%) medium, 45 (23%) low, and 89 (46%) none. Demographics and transplant characteristics were evenly matched between the CHG usage groups with the exception that high usage groups were more likely to receive levofloxacin for antibiotic prophylaxis (p=0.003). Increased CHG usage was significantly associated with decreased incidence of clinically-significant infection (p=0.006), CLABSI (p=0.04), and MBI-LCBI (p=0.002) (Table 1). Multivariate analysis did not demonstrate a significant contribution of antibiotic prophylaxis regimen. No significant difference was found between CHG usage groups in median days to stem cell engraftment, incidence of febrile neutropenia or C. difficile infection, or rashes requiring medical treatment. There were no rashes attributable to CHG usage. Among patients who were VRE rectal swab negative on admission, there was a significant trend toward lower rates of VRE acquisition with increasing CHG usage (High CHG 13.6% vs No CHG 25.3%, p=0.02). Discussion: Increased CHG usage is associated with a significant trend toward lower rates of clinically-significant infection, CLABSI, MBI-LCBI, and VRE colonization in adult inpatients undergoing HSCT. Effects are most strongly seen at &gt;75% daily CHG usage. There were no adverse effects due to CHG application. The significant decrease in MBI-LCBI with topical CHG suggests an interaction between the skin microbial environment and enteric organisms. Therefore, further research exploring the effects of CHG on the skin and gut microbiota is warranted. Disclosures Gasparetto: BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

Management of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBIs) in Stem Cell Transplant Recipients: A National Survey of Cancer Centers Practices

Background Patients with hematologic malignancies receiving chemotherapy and those undergoing stem cell transplantation (SCT) are at risk for mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs). Our comprehensive cancer center, which performs over 300 SCTs per year, has historically removed central venous catheters (CVCs) for the majority of transient MBI- LCBI cases in SCT recipients. However, given the lack of evidence-based guidelines for removal or salvage, we created a national survey to gauge current clinical practice of MBI-LCBI and CVC management among U.S. cancer centers. Methods We created a 22-item online anonymous survey via Qualtrics software. The survey was performed in August and September of 2018 and open for a total of 30 days. The questionnaire consisted of three parts: respondents' characteristics, MBI-LCBI and CVC clinical practice questions, and two clinical vignettes. In parallel, a quality improvement project is ongoing to evaluate outcomes following catheter salvage versus removal in MBI-LCBI cases of SCT recipients. Results The survey was distributed to seventy Infectious Diseases consultants at cancer centers in the United States. The response rate was 44%. 70% of respondents had > 5 years of clinical experience. The majority (75%) responded that MBI-LCBI does not implicate the CVC as the source of bacteremia. 61% of respondents salvage CVCs in SCT patients unless contraindicated. In patients with salvaged CVCs, 37.5% of responders do not use adjunct lock therapy and 46% deem repeat end of therapy surveillance blood culture as unnecessary. 62.5% of responders do not routinely recommend other procedures such as venous duplex ultrasound and transthoracic echocardiogram for MBI-LCBI cases unless clinically indicated. Among 90% of respondents deemed fluoroquinolone step down oral therapy for susceptible Enterobacteriaceae MBI-LCBI as acceptable. Conclusion Management of MBI-LCBIs in hematologic malignancies and SCT patients is variable but CVC salvage is considered by a majority of survey respondents as a safe approach. Data comparing outcomes of catheter salvage strategies are lacking. Results of our ongoing quality improvement project will provide further guidance.

Modulation of the Oral Microbiome to Improve Oral Health and Reduce BSI from Oral Flora in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Randomized Controlled Trial

BackgroundBlood stream infections (BSI) in hematopoietic stem cell transplant (HSCT) patients with central venous catheters may arise from translocation of bacteria through a non-intact gastrointestinal mucosa and are known as mucosal barrier injury–laboratory confirmed blood stream infections (MBI-LCBI). Central venous catheter maintenance care doesn't prevent MBI-LCB and currently there are no proven strategies to prevent bacteremia secondary to mucosal barrier injury. Gingivitis and periodontitis are features of the mucosal toxicity seen post-HSCT and are associated with BSI frequency. Xylitol is a non-fermentable polysaccharide that reduces dental caries, plaque accumulation, and oral disease progression by inhibiting bacterial growth and community development. We hypothesized that daily dental xylitol, in addition to current oral care practice, is effective at reducing gingivitis, periodontitis and BSI from oral organisms.MethodsWe performed a prospective randomized controlled trial to test our hypothesis. All patients received standard oral care and half were randomized to additionally receive daily xylitol. Oral exams were performed at baseline and at intervals for the first 28 days post-HSCT. Metagenomic shotgun sequencing of gingival samples was performed at these same intervals. For patients who develop BSI, whole genome sequencing of bacterial isolates is being performed to assess for genetic relatedness to corresponding strains present within the patient's oral microbiome preceding the infection.ResultsWe enrolled 35 patients, 17 cases and 18 controls before ending the study early for efficacy. Five patients withdrew from the study (3 cases, 2 controls). Patients who received xylitol had a significantly lower rate of gingivitis, oral plaque and oral ulcers greater than 10 mm. There was a significant decrease in BSI from oral organisms in the first 30 days post HSCT in the xylitol group, 0/14 (0%) vs 5/16 (31%) (p = 0.04). Preliminary microbiome analysis showed decrease relative abundance of Candida albicans in patients receiving xylitol and individual patient analysis shows that xylitol may also impede Streptococcus mitis/oralis dominance in the oral microbiome. Additionally, we found that Staphylococcus aureus, a common cause of Central Line Associated Blood Stream Infection (CLABSI), was prominent in several gingival samples, suggesting BSI with Staphylococcus aureus may indeed be related to mucosal barrier injury.ConclusionsThe addition of xylitol to oral standard care appears to decrease BSI secondary to oral organisms, dental plaque, gingivitis and oral ulcerations in patients undergoing SCT. Blood stream infections (BSI) in hematopoietic stem cell transplant (HSCT) patients with central venous catheters may arise from translocation of bacteria through a non-intact gastrointestinal mucosa and are known as mucosal barrier injury–laboratory confirmed blood stream infections (MBI-LCBI). Central venous catheter maintenance care doesn't prevent MBI-LCB and currently there are no proven strategies to prevent bacteremia secondary to mucosal barrier injury. Gingivitis and periodontitis are features of the mucosal toxicity seen post-HSCT and are associated with BSI frequency. Xylitol is a non-fermentable polysaccharide that reduces dental caries, plaque accumulation, and oral disease progression by inhibiting bacterial growth and community development. We hypothesized that daily dental xylitol, in addition to current oral care practice, is effective at reducing gingivitis, periodontitis and BSI from oral organisms. We performed a prospective randomized controlled trial to test our hypothesis. All patients received standard oral care and half were randomized to additionally receive daily xylitol. Oral exams were performed at baseline and at intervals for the first 28 days post-HSCT. Metagenomic shotgun sequencing of gingival samples was performed at these same intervals. For patients who develop BSI, whole genome sequencing of bacterial isolates is being performed to assess for genetic relatedness to corresponding strains present within the patient's oral microbiome preceding the infection. We enrolled 35 patients, 17 cases and 18 controls before ending the study early for efficacy. Five patients withdrew from the study (3 cases, 2 controls). Patients who received xylitol had a significantly lower rate of gingivitis, oral plaque and oral ulcers greater than 10 mm. There was a significant decrease in BSI from oral organisms in the first 30 days post HSCT in the xylitol group, 0/14 (0%) vs 5/16 (31%) (p = 0.04). Preliminary microbiome analysis showed decrease relative abundance of Candida albicans in patients receiving xylitol and individual patient analysis shows that xylitol may also impede Streptococcus mitis/oralis dominance in the oral microbiome. Additionally, we found that Staphylococcus aureus, a common cause of Central Line Associated Blood Stream Infection (CLABSI), was prominent in several gingival samples, suggesting BSI with Staphylococcus aureus may indeed be related to mucosal barrier injury. The addition of xylitol to oral standard care appears to decrease BSI secondary to oral organisms, dental plaque, gingivitis and oral ulcerations in patients undergoing SCT.

Burden and Outcomes of Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections (MBI-LCBI) in the First 100 Days after Allogeneic Stem Cell Transplant: A CIBMTR Analysis

Background: Patients undergoing stem cell transplant (SCT) are at risk of bloodstream infections (BSI). BSI led to prolonged hospitalization, intensive care admissions, prolonged antibiotic treatment and increased mortality. Recently, the Centers for Disease Control and Prevention developed a modification of the Central line associated bloodstream infection (CLABSI) definition, termed “mucosal barrier injury laboratory-confirmed bloodstream infection” (MBI-LCBI) to differentiate BSI likely related to mucosal barrier injury. BSI are identified as an MBI-LCBI if: (1) it resulted from 1 or more of a group of selected organisms known to be commensals of the oral cavity or gastrointestinal tract and (2) occurred in a patient with signs or symptoms compatible with the presence of mucosal barrier injury such as gastrointestinal graft-versus-host disease and/or neutropenia. We utilized the CIBMTR database to determine the incidence and timing of MBI-LCBI, risk factors for development of MBI-LCBI, and compare transplant outcomes by 1 year after SCT.Methods: We identified 16,875 pediatric and adult patients receiving first allogeneic transplant from 2009-2016. Patients were classified into 4 categories based on the occurrence of BSI in first 100 days: MBI-LCBI (n=1434; 8.5%), MBI-LCBI +other BSI (n=700; 4.1%), BSI only (n=3016; 17.8%), and control (n=11725; 69.5%) (Figure 1). Demographics and outcomes, including overall survival (OS), chronic GVHD, and transplant-related mortality (TRM, for malignant disease patients only), were compared between groups.Results: The cumulative incidence of MBI-LCBI was 13% (99% CI: 12-13%) by day 100 whereas the probability for another BSI not meeting MBI-LCBI criteria was 22% (99% CI: 21-23%) by day 100. The median time from transplant to first MBI-LCBI was 8 days (<1-98), MBI-LCBI + other BSI 10 days (<1-99), and other BSI was 38 days (<1-100). Karnofsky/Lansky performance status <90 [RR 1.21 (99% CI: 1.06 - 1.38)], myeloablative conditioning [RR 1.45 (99% CI: 1.27-1.69)], post-transplant cyclophosphamide as GVHD prophylaxis [RR 1.83 (99% CI: 1.40 - 2.39)], and receipt of cord blood [RR 2.89 (99% CI: 2.06 - 4.06)] were associated with a significant increase in the risk of MBI-LCBI (Table 1). The 1 year OS was inferior for patients with MBI-LCBI only [59% (99% CI: 56 - 61%); RR 1.86 (99% CI: 1.65 - 2.09)], Other BSI only [60% (99% CI: 58 - 63%); RR 1.86 (99% CI: 1.70 - 2.04)], and MBI-LCBI + Other BSI [46% (99% CI: 41 - 50%); RR 2.79 (99% CI: 2.42 - 3.23)] compared to controls [72% (71 - 73); p <0.0001] (Table 2). There was no impact of MBI-LCBI only, Other BSI only, or MBI-LCBI + Other BSI compared to controls on development of chronic GVHD. As expected 1 year TRM in patients with malignant disease was increased with any BSI but was similar for patients with MBI-LCBI only [30% (99% CI: 27 - 34%); RR 2.41 (99% CI: 2.05-2.82] or Other BSI [25% (99% CI: 23 - 27%); RR 2.20 (1.94 - 2.51)] and further worsened for patients with both MBI-LCBI + Other BSI [45% (99% CI: 39 - 50%); RR 4.23 (3.53 - 5.07)] compared to controls [16% (99% CI:15 - 17%)]. Finally, infection as a cause of mortality was higher in patients with MBI-LCBI (19%), BSI only (17%), and MBI-LCBI + BSI (21%) then controls (12%).Discussion: Our data demonstrate approximately 13% of all patients develop at least one MBI-LCBI and an additional 22% of patients develop another BSI in the first 100 days post SCT. Multivariable analysis revealed increased risk of MBI-LCBI with poor performance status, cord blood grafts, myeloablative conditioning, and post-transplant cyclophosphamide GVHD prophylaxis. BSI, whether or not MBI-LCBI, significantly decreases overall survival, primarily related to an increased TRM. The combination of MBI-LCBI and other BSI worsens both TRM and OS, but the respective impact of MBI-LCBI only was similar to Other BSI only. BSI, both MBI-LCBIs and other BSI, lead to significant morbidity and mortality and healthcare resource utilization. Reduction in frequency of BSI should be a major public health and scientific priority. [Display omitted] DisclosuresPerales:Novartis: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Abbvie: Other: Personal fees; Takeda: Other: Personal fees; Merck: Other: Personal fees.

Mucosal Barrier Injury Laboratory Confirmed Bloodstream Infections

To increase the awareness of the new CDC survey definition of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection (MBI-LCBI). We included a comparison of the definition of Central Line-Associated Bloodstream Infection (CLABSI), with a high sensitivity but low specificity and Catheter-Related Bloodstream Infection (CRBSI). There are other parameters like the difference between the size of the inoculum (catheter lumen vs peripheral), that increased specificity and is useful for research and clinical decisions. Also, MBI-LCBI secondary to bacterial translocation in patients who had received myeloablative chemotherapy with severe neutropenia is not related to central venous catheter care. This new survey definition is useful for better classification of nosocomial bloodstream infections among patients receiving myeloablative chemotherapy and has impacted diminishing the incidence of CLABSI, which has probably has been overestimated in patients with hematological malignancies. The concept of MBI-LCBI should not be limited to survey purposes; it is also useful for clinical decisions. We propose to incorporate a second set of blood cultures obtained 48 hours after antibiotic treatment onset, one through the line of the CVC and another one at a peripheral site; if negative, it avoids unnecessary removal of the catheter in patients with severe neutropenia or, on the contrary, if positive blood cultures persist after 48 hours of antimicrobial therapy, there is a clear indication for central venous catheter removal. The definition of MBI-LCBI avoids over-diagnosis of CLABSI in patients receiving myeloablative chemotherapy with severe neutropenia.

Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) on central line-associated bloodstream infections (CLABSIs) in department of hematology at single university hospital in Japan.

Central line-associated bloodstream infections (CLABSIs) are among the most serious complications especially in blood cancer patients. In January 2013, Centers for Disease and Prevention (CDC) introduced a new surveillance definition of mucosal barrier injury-associated laboratory-confirmed bloodstream infection (MBI-LCBI). This study was to determine the impact of MBI-LCBI on CLABSIs and compare the clinical characteristics of MBI versus non-MBI-LCBI cases. We retrospectively reviewed the records of 250 consecutive patients. They were admitted in department of hematology at Aichi Medical University Hospital. We applied the revised 2013 CLABSI surveillance protocol to all CLABSI cases identified during the 47-months period from May 2012 through June 2016. A total of 44 CLABSIs were identified. The median patient age was 65 years (range, 12 to 89). Among 44 patients, 31 patients were diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%). A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were classified as non-MBI-LCBI. The primary disease type (P=0.018), neutropenic within 3 days before CLABSI (MBI-LCBI vs. non-MBI-LCBI: 95.0% vs. 26.3%, P=<0.0001), line(s) removed owing to CLABSI (15.0% vs. 54.2%, P=0.011) and Gram-negative organisms cultured (70.0% vs. 37.5%, P=0.004) showed significantly difference between the groups. Our data showed that MBI-LCBI cases account for 45.5% of the CLABSI cases identified in blood cancer patients, and constituted a significant burden to this high-risk patient population.

Impact of removing mucosal barrier injury laboratory-confirmed bloodstream infections from central line-associated bloodstream infection rates in the National Healthcare Safety Network, 2014.

Central line-associated bloodstream infection (CLABSI) event data reported to the National Healthcare Safety Network from 2014, the first year of required use of the mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) definition, were analyzed to assess the impact of removing MBI-LCBI events from CLABSI rates. CLABSI rates decreased significantly in some location types after removing MBI-LCBI events, and MBI-LCBI events will be removed from publicly reported CLABSI rates.

Healthcare Burden, Risk Factors, and Outcomes of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections after Stem Cell Transplantation

Mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs) lead to significant morbidity, mortality, and healthcare resource utilization in hematopoietic stem cell transplant (HSCT) patients. Determination of the healthcare burden of MBI-LCBIs and identification of patients at risk of MBI-LCBIs will allow researchers to identify strategies to reduce MBI-LCBI rates. The objective of our study was to describe the incidence, risk factors, timing, and outcomes of MBI-LCBIs in hematopoietic stem cell transplant patients. We performed a retrospective analysis of 374 patients who underwent HSCT at a large free-standing academic children's hospital to determine the incidence, risk factors, and outcomes of patients that developed a bloodstream infection (BSI) including MBI-LCBI, central line–associated BSI (CLABSI), or secondary BSI in the first year after HSCT. Outcome measures included nonrelapse mortality (NRM), central venous catheter removal within 7 days of positive culture, shock, admission to the pediatric intensive care unit (PICU) within 48 hours of positive culture, and death within 10 days of positive culture. One hundred seventy BSIs were diagnosed in 100 patients (27%): 80 (47%) MBI-LCBIs, 68 (40%) CLABSIs, and 22 (13%) secondary infections. MBI-LCBIs were diagnosed at a significantly higher rate in allogeneic HSCT patients (18% versus 7%, P = .007). Reduced-intensity conditioning (OR, 1.96; P = .015) and transplant-associated thrombotic microangiopathy (OR, 2.94; P = .0004) were associated with MBI-LCBI. Nearly 50% of all patients with a BSI developed septic shock, 10% died within 10 days of positive culture, and nearly 25% were transferred to the PICU. One-year NRM was significantly increased in patients with 1 (34%) and more than 1 (56%) BSIs in the first year post-HSCT compared with those who did not develop BSIs (14%) (P ≤ .0001). There was increased 1-year NRM in patients with at least 1 MBI-LCBI (OR, 1.94; P = .018) and at least 1 secondary BSI (OR, 2.87; P = .0023) but not CLABSIs (OR, 1.17; P = .68). Our data demonstrate that MBI-LCBIs lead to substantial use of healthcare resources and are associated with significant morbidity and mortality. Reduction in frequency of MBI-LCBI should be a major public health and scientific priority.