Incidence Of Bloodstream Infections Research Articles

Developing a multiplex PCR-based assay kit for bloodstream infection by analyzing genomic big data.

BackgroundIn recent years, the incidence of bloodstream infections (BSI) has increased, the composition of pathogenic bacteria has changed, and drug resistance among bacteria has gradually increased due to the widespread use of interventional techniques, broad‐spectrum antibacterial drugs, hormones, and immunosuppressive agents. Here, we have developed a multiplex PCR assay kit for the detection of pathogens (14 Gram‐negative bacteria, 15 Gram‐positive bacteria, and 4 fungi) in whole blood from patients with BSI using five‐color fluorescent multiplex PCR followed by capillary electrophoresis. Our assay exhibits a diagnosis of higher quality and an improved detection rate for common pathogens.MethodsA local genome DNA database of 33 pathogenic bacteria was constructed. Next, “Exhaustive” primer search of the full coding sequence of the reference genomes of these bacteria was performed. Panels with minimal interactions between primers and amplicons were selected by random sampling and testing by a recursive algorithm. Primers and Mg2+ concentrations and PCR reaction procedures were optimized to maximize the detection efficacy.ResultsThe LOD of the kit was determined as 100 copies/μl. Using clinical samples, results generated by this kit and regular blood culture method were found to be 95.08% consistent. Additionally, six pathogens which were unidentifiable by blood culture were successfully detected by this kit.ConclusionOur study provided a bioinformatics approach to the challenge of primer design in multiplex PCR, and combined with optimized wet lab practice, a multiplex PCR‐based assay kit for BSI with higher sensitivity and accuracy than blood culture was produced.

Antimicrobial use and aetiology of bloodstream infections in critically ill patients during early stages of SARS-CoV-2 pandemic

BackgroundDuring early stages of COVID-19 pandemic, antimicrobials were commonly prescribed.AimTo describe clinical, microbiological and antimicrobial use changes in bloodstream infections (BSI) of ICU patients during the first wave of COVID-19 pandemic compared to pre-COVID-19 era.MethodsObservational cohort study of patients admitted to ICU of Bellvitge University Hospital was conducted during the COVID-19 pandemic (March-June 2020) and before COVID-19 pandemic (March-June 2019). Differences in clinical characteristics, antimicrobial consumption and incidence and aetiology of BSI were measured.FindingsCOVID-19 patients had significantly less comorbidities with obesity the only risk factor that increased in frequency. COVID-19 patients more frequently required invasive supportive care measures, had longer median ICU stay and higher mortality rates. The incidence of BSIs was higher in COVID-19 period (RR 3.2 [95%CI 2.2–4.7]), occurred in patients who showed prolonged median ICU stay (21days) and was associated with high mortality rate (47%). The highest increases in the aetiological agents were observed for AmpC-producing bacteria (RR 11.1 [95%CI 2.6–47.9]) and non-fermenting rods (RR 7.0 [95%CI 1.5–31.4]). The emergence of bacteraemia caused by Gram-negative rods resistant to amoxicillin-clavulanate, which was used as empirical therapy during early stages of the pandemic, led to an escalation towards broader-spectrum antimicrobials such as meropenem and colistin which was also associated with the emergence of resistant isolates.ConclusionsThe epidemiological shift towards resistant phenotypes in critically ill COVID-19 patients was associated with the selective use of antimicrobials. Our study provides evidence of the impact of empirical therapy on the selection of bacteria and their consequences on BSI over the subsequent months.

Scheduled removal of central venous catheters (CVC) to prevent CVC-related bloodstream infections in patients with hematological disease or autologous stem cell transplantation: a registry-based randomized simulation-study

Although not generally recommended, scheduled central venous catheter (CVC) removal is sometimes carried out in order to reduce the CVC-related bloodstream infection (CRBSI) incidence. We conducted a simulation for scheduled CVC removal within the multicenter CRBSI registry (SECRECY). Non-tunneled jugular and subclavian CVC in patients with hematological disease or with germ cell tumors (including patients receiving autologous stem cell transplantation [SCT]) were included. Cases were randomized in a 1:1:1:1 ratio to either a simulated, scheduled CVC removal after 7, 14, and 21 days, or to non-simulated, unscheduled CVC removal (control group). The primary endpoint was definitive CRBSI incidence for a scheduled CVC removal after 14 days (dCRBSI-D14rmv). Among other, secondary endpoints were definite CRBSI incidence for a scheduled removal after 7 days (dCRBSI-D7rmv) and 21 days (dCRBSI-D21rmv). Data on 2984 CVC were included. Patients’ median age was 59 (range 16–95) years, 58.8% being male. The vast majority (98.4%) were patients with hematological malignancies. Jugular veins were the main insertion site (93.2%). dCRBSI-D14rmv was 3.10/1000 CVC days as compared to 4.15/1000 CVC days in the control group (p = 0.23). There was a significant difference between dCRBSI-D7rmv (0.86/1000 CVC days) and controls (p < 0.001), but not between dCRBSI-D21rmv (4.10/1000 CVC days) and controls (p = 0.96). Our data suggest that in patients with hematological diseases or autologous SCT recipients scheduled CVC removal after 14 days does not result in a lower CRBSI incidence compared to unscheduled removal.Trial registration: DRKS00006551, 2014/09/29, retrospectively registered.

Reducing central-line-associated bloodstream infections by half: it is possible

Healthcare-associated bloodstream infection (BSI) and especially central-line-associated bloodstream infection (CLABSI) are known to be preventable in up to 70% of cases [ 1 Pronovost P.J. Watson S.R. Goeschel C.A. Hyzy R. Berenholtz S. Sustaining reductions in central-line associated bloodstream infections in Michigan intensive care units: a 10-year analysis. Am J Med Qual. 2016; 31: 197-202 Crossref PubMed Scopus (63) Google Scholar , 2 Latif A.L. Kelly B. Edrees H. Kent P. Weaver S. Jovanovic B. et al. Implementing a multifaceted intervention to decrease central line associated bloodstream infection in SEHA (Abu Dhabi Health Services Company) intensive care units: the Abu Dhabi experience. Infect Control Hosp Epidemiol. 2015; 36: 816-822 Crossref PubMed Scopus (21) Google Scholar , 3 Umscheid C.A. Mitchell M.D. Doshi J.A. Agarwal R. Williams K. Brennan P. Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs. Infect Control Hosp Epidemiol. 2011; 32: 101-114 Crossref PubMed Scopus (673) Google Scholar ]. In acute care hospitals, mean CLABSI rates of 1.44–20.90 per 1000 central-line-days (CLD) in the intensive care units (ICUs) of the International Nosocomial Infection Control Consortium (2010–2015) have been reported [ [4] Rosenthal V. Al-Abdely H. El-Kholy A.A. Aziz AlKhawaja S.A. Leblebicioglu H. Mehta Y. et al. International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010–2015: device-associated module. Am J Infect Control. 2016; 44: 1495-1504 Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar ]. The Belgian incidence of healthcare-associated BSI, at 8.4 per 10,000 patient-days, has changed little during recent years in acute care hospitals (www.nsih.be). One healthcare-associated BSI out of four was classified as CLABSI. At University Hospitals Leuven, surveillance of CLABSI started in the year 2012. Because of an initially high CLABSI rate of 4.4 and 6.1 per 1000 CLD in non-ICU and ICU units respectively, a hospital-wide quality improvement project was initiated.

Incidence and Risk Factors for Blood Stream Infection in Mechanically Ventilated COVID-19 Patients.

It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the number of secondary infections in COVID-9 patients may be higher. This retrospective analysis was conducted to determine the incidence of BSI. Furthermore, risk factors, mortality, and other outcomes were analyzed. The setting was an Intensive Care Unit (ICU) at a University Hospital. Patients suffering from SARS-CoV-2 infection and requiring mechanical ventilation (MV) for >48 h were eligible. The characteristics of patients who presented BSI were compared with those of patients who did not present BSI. Eighty-four patients were included. The incidence of BSI was 57%. In most cases, multidrug-resistant pathogens were isolated. Dyslipidemia was more frequent in the BSI group (p < 0.05). Moreover, BSI-group patients had a longer ICU stay and a longer duration of both mechanical ventilation and sedation (p < 0.05). Deaths were not statistically different between the two groups (73% for BSI and 56% for the non-BSI group, p > 0.05). Compared with non-survivors, survivors had lower baseline APACHE II and SOFA scores, lower D-dimers levels, a higher baseline compliance of the respiratory system, and less frequent heart failure. They received anakinra less frequently and appropriate therapy more often (p < 0.05). The independent risk factor for mortality was the APACHE II score [1.232 (1.017 to 1.493), p = 0.033].

Changes in the incidence of Candida-related central line-associated bloodstream infections in pediatric intensive care unit: Could central line bundle have a role?

Candida species are among the most prevalent microorganisms in pediatric critical care units that cause central line-associated bloodstream infections . The goal of this study was to assess the therapeutic benefit of central line bundle for the prevention of Candida species-related bloodstream infections in pediatric intensive care units. The study covered the period from January 1, 2009, to December 31, 2019. Pre-bundle and bundle phases were included in the research. The Clinical Microbiology Laboratory's records revealed episodes of Candida-related central line-associated bloodstream infections. The study was conducted in the Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital's PICU (which has 24 beds and admits 350 patients per year). This study included pediatric patients in the pediatric intensive care unit with non-tunneled central venous catheters . In the pediatric intensive care unit, a central line bundle was started. A total of 236 Candida-related central line-associated bloodstream infections were discovered during the study period. Non-albicans Candida accounted for 83.5% (197) of the total, whereas C.albicans accounted for 16.5%(39). During the pre-bundle period, 137 Candida species were isolated from the patients, while 99 Candida species were isolated during the bundle period. Candida-related central line-associated bloodstream infections dropped from 13.68 to 5.93 per 1000 CL-days after the central line bundle was used ( p < 0.001). According to our findings, the central line bundle greatly reduced central line-associated Candida species bloodstream infections. Central line bundles are an effective scientific solution for preventing Candida-related central line-associated bloodstream infections in hospitals with high Candida prevalence.

Zuragen™ antiseptic catheter lock: A bridge too far?

When sodium citrate is used as an anticoagulant catheter lock the best concentration is 7%, since this provides a density approximately the same as blood. Our laboratory found that the addition of methylene blue and parabens greatly augmented antibacterial properties. Ash Access sponsored a randomized clinical trial in 400 dialysis patients with tunneled CVC, and this showed a significant decrease in incidence of catheter-related bloodstream infection (CRBSI) defined by stringent criteria. The FDA decided that the study missed its primary endpoint, and that the product was mis-classified, so they did not give approval to market. The licensee decided not to appeal to the decision to the physician panel and ended support of the project. Rights to market the catheter lock eventually returned to Ash Access.

The impact of tocilizumab treatment for cytokine release syndrome on the incidence of early blood stream infections after peripheral blood haploidentical hematopoietic cell transplantation

Cytokine release syndrome (CRS) is a potentially fatal systemic inflammatory response that can occur in patients undergoing peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT). Severe CRS has previously been associated with increased infection risk. IL-6 inhibitors, such as tocilizumab, are useful in moderate to severe CRS, but their effect on infection risk has not been established in this setting. We examined the effect of tocilizumab on blood stream infections (BSIs) in the early post-transplant period in 235 patients who underwent haplo-HCT from 2013 to 2020. Mild CRS was associated with a lower incidence of BSI than severe CRS (OR 0.31, 95% CI 0.13–0.74). In the tocilizumab group, 31% of patients had positive blood cultures versus 14% in the non-tocilizumab group (OR 1.61, 95% CI 0.30–8.60, p = 0.58). However, when controlling for CRS grade, tocilizumab was not independently associated with increased rates of BSIs, suggesting it does not further increase infection risk.

Incidence of bloodstream infections in patients with COVID-19: a retrospective cohort study of risk factors and outcomes.

Prior evidence found that bloodstream infections (BSIs) are common in viral respiratory infections and can lead to heightened morbidity and mortality. We described the incidence, risk factors, and outcomes of BSIs in patients with COVID-19. This was a single-center retrospective cohort study of adults consecutively admitted from March to June 2020 for COVID-19 with BSIs. Data were collected by electronic medical record review. BSIs were defined as positive blood cultures (BCs) with a known pathogen in one or more BCs or the same commensal organism in two or more BCs. We evaluated 290 patients with BCs done; 39 (13.4%) had a positive result. In univariable analysis, male sex, black/African American race, admission from a facility, hemiplegia, altered mental status, and a higher Charlson Comorbidity Index were positively associated with positive BCs, whereas obesity and systolic blood pressure (SBP) were negatively associated. Patients with positive BCs were more likely to have severe COVID-19, be admitted to the intensive care unit (ICU), require mechanical ventilation, have septic shock, and higher mortality. In multivariable logistic regression, factors that were independent predictors of positive BCs were male sex (OR=2.8, p=0.030), hypoalbuminemia (OR=3.3, p=0.013), ICU admission (OR=5.3, p<0.001), SBP<100 mmHg (OR=3.7, p=0.021) and having a procedure (OR=10.5, p=0.019). Patients with an abnormal chest X-ray on admission were less likely to have positive BCs (OR=0.3, p=0.007). We found that male sex, abnormal chest X-ray, low SBP, and hypoalbuminemia upon hospital admission, admission to ICU, and having a procedure during hospitalization were independent predictors of BSIs in patients with COVID-19.

Bloodstream Infections in a COVID-19 Non-ICU Department: Microbial Epidemiology, Resistance Profiles and Comparative Analysis of Risk Factors and Patients' Outcome.

Background: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. Methods: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. Results: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86–119.21), p < 0.001]. Conclusions: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition.

Central Venous Catheter Related Bloodstream Infections in Medical Intensive Care Unit Patients in a Tertiary Referral Centre

To determine the incidence of central line associated bloodstream infections (CLABSIs) in the medical intensive care unit (ICU) and ward setting at All India Institute of Medical Sciences (AIIMS), New Delhi. The study was conducted in the medical ICU, a 9-bedded ICU at the AIIMS, a tertiary care teaching hospital. The study design was a prospective observational study. One hundred patients admitted to medical ICU and the ward at AIIMS with an indwelling, non-tunnelled central venous catheter (CVC) in place at admission and those with a hospital stay with indwelling CVC for more than 48 hours were monitored. These patients were followed daily for the development of new onset sepsis 48 hours after insertion of CVC, in which case three sets of blood samples for culture were drawn over a span of 24 hours. Incidence of CLABSIs was measured per 1000 central line days. One hundred patients hospitalised for an aggregate 1119 days acquired 29 hospital-acquired infections (HAIs), a rate of 38.8% or 31.2 HAIs per 1000 hospital days. The incidence of bloodstream infections (BSIs) in this group was 6.8%. No case of laboratory confirmed CLABSIs could be demonstrated. Incidence of clinical sepsis was 27.6% or 8.2 per 1000 CVC days. There were 9 cases out of the 29 patients (39.7%) who had evidence of HAIs with no apparent focus of infection. Only one of these cases had evidence of BSI with isolation of Staphylococcus aureus in both CVC tip culture and the simultaneous blood culture; however the antibiograms were different. The low rate of BSIs in the present study and the absence of occurrence of a laboratory confirmed CLABSI should be interpreted in the light of the small sample size of the study and the multitude of antibiotics received before the development of HAI.

Multidrug-Resistant Acinetobacter baumannii May Cause Patients to Develop Polymicrobial Bloodstream Infection.

Background The incidence of polymicrobial bloodstream infections is increasing, the clinical characteristics of polymicrobial Acinetobacter baumannii bloodstream infections (AB-BSI) are unclear, and there are no reports of polymicrobial AB-BSI in mainland China. Therefore, our objective was to identify the clinical characteristics, risk factors, and outcomes of polymicrobial AB-BSI versus monomicrobial AB-BSI. Methods A retrospective survey of all patients with AB-BSI from January 1, 2015, to December 31, 2019, and their clinical data were collected and analyzed by reviewing electronic medical records. All data were compared and analyzed between groups of monomicrobial and polymicrobial AB-BSI. Risk factors for polymicrobial AB-BSI were assessed using multivariable logistic regression analysis. Results A total of 204 patients were included, of which 39 (19.1%) were patients with polymicrobial AB-BSI. The main sources of the pathogenicity of polymicrobial Acinetobacter baumannii bloodstream infections were skin and soft tissue (38.5% vs. 16.4%, p=0.002). Resistance to piperacillin/tazobactam as an independent factor for polymicrobial AB-BSI was found in multivariate analysis. Patients with polymicrobial AB-BSI had longer hospital stays compared to those with monomicrobial AB-BSI. However, there was no significant difference in mortality between the two groups. Conclusions Polymicrobial AB-BSI accounted for a significant proportion among all AB-BSI, and it did not influence mortality but was related to slightly longer total hospital stays. Multidrug resistance was associated with the development of polymicrobial AB-BSI but does not directly lead to polymicrobial AB-BSI, whereas resistance to piperacillin/tazobactam was highly correlated with polymicrobial AB-BSI. Therefore, while treating A. baumannii bloodstream infections, clinicians cannot ignore the multidrug-resistant A. baumannii, especially piperacillin/tazobactam-resistant A. baumannii, which may predispose to the development of polymicrobial AB-BSI.

P1575: DEVELOPMENT OF A RISK PREDICTION MODEL OF SUBSEQUENT BLOOLDSTREAM INFECTION AFTER CARBAPENEM-RESISTANT ENTEROBACTERIACEASE ISOLATED FROM PERIANAL SWABS IN PATIENTS WITH HEMATOLOGICAL DISEASES

Background: Hematological patients are at higher risk of developing carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) and associated with high mortality. Prediction model for a subsequent CRE BSI in hematological patients with CRE isolated from previous perianal swab samples can provide timely and useful target treatment strategies. Aims: To developing a quantified risk prediction model based on the risk factors of subsequent BSI in CRE carriers will help clinicians better identify specific individuals who would truly benefit from early, empiric CRE-targeted treatment. Methods: The data were extracted from patients with CRE isolated from perianal swab samples at the Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between July 2017 to October 2020 January. Patients who developed subsequent CRE BSI were compared with those who did not develop BSI. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of clinical factors. Results: A total of 215 cases were included and 29 (13.4%) patients of them with CRE isolated from perianal swab samples developed CRE BSI subsequently. Multivariate analysis showed that C-reactive protein(CRP)﹥30mg/l(OR 10.613，95%CI 2.965~37.985，P=0.000）, perianal infection(OR 6.450, 95%CI 2.223~18.714, P=0.001), concomitant gastrointestinal symptoms (OR 4.175，95%CI 1.476~11.813，P=0.007），age﹥44 years (OR 3.415，95%CI 1.222~9.541，P=0.007）and neutrophil count﹤0.025×109/L (OR 4.583，95%CI 0.939~22.369，P=0.060）were risk factors for CRE BSI in patients with CRE isolated from perianal swab samples (P<0.01). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.921 (0.851-0.968，P<0.001). Image:Summary/Conclusion: Hematological patients with CRE isolated from perianal swab samples have a relatively low incidence of subsequent BSI but a relatively high risk of death. The risk prediction model based on CRP, perianal infection, concomitant gastrointestinal symptoms, age and valley absolute neutrophil may be used for predicting subsequent CRE BSI in patients with isolated from perianal swab samples and provide timely and effective treatment reference for this kind of patients.

Risk factors for unplanned removal of central venous catheters in hospitalized children with hematological and oncological disorders.

Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs) and tunneled CVCs, to propose which is the better device. We followed 89 patients fitted with a tunneled CVC (total 21,395 catheter-days) and 84 fitted with a PICC (total 9177 catheter-days) between January 1, 2013 and December 31, 2015, until catheter removal. Patients with a PICC had a significantly higher 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08 × 10-3) and total unplanned removals (29.0% vs. 6.9%, p = 0.0316) than those with tunneled CVCs. However, the cumulative incidence of central line-associated bloodstream infection did not differ significantly by CVC type. Multivariable analysis identified younger age (< 2years) [sub-distribution hazard ratio (SHR) 2.29; 95% confidence interval (CI) 1.27-4.14] and PICC (SHR 2.73; 95% CI 1.48-5.02) as independent risk factors for unplanned removal. Thus, our results suggest that tunneled CVCs are preferable in pediatric patients with hematological and oncological disorders requiring long-term, intensive treatment.

Results of an Innovative Program for Surveillance, Prophylaxis, and Treatment of Infectious Complications Following Allogeneic Stem Cell Transplantation in Hematological Malignancies (BATMO Protocol).

BackgroundInfectious complications are a significant cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-SCT). The BATMO (Best-Antimicrobial-Therapy-TMO) is an innovative program for infection prevention and management and has been used in our centre since 2019. The specific features of the BATMO protocol regard both prophylaxis during neutropenia (abandonment of fluoroquinolone, posaconazole use in high-risk patients, aerosolized liposomal amphotericin B use until engraftment or a need for antifungal treatment, and letermovir use in CMV-positive recipients from day 0 to day +100) and therapy (empirical antibiotics based on patient clinical history and colonization, new antibiotics used in second-line according to antibiogram with the exception of carbapenemase-producing K pneumoniae for which the use in first-line therapy is chosen).MethodsData on the infectious complications of 116 transplant patients before BATMO protocol (Cohort A; 2016 - 2018) were compared to those of 84 transplant patients following the introduction of the BATMO protocol (Cohort B; 2019 - 2021). The clinical and transplant characteristics of the 2 Cohorts were comparable, even though patients in Cohort B were at a higher risk of developing bacterial, fungal, and CMV infections, due to a significantly higher proportion of myeloablative regimens and haploidentical donors.ResultsNo change in the incidence of infections with organ localization was observed between the two Cohorts. A significant reduction in Clostridioides difficile infections by day +100 was observed in Cohort B (47% vs. 15%; p=0.04). At day +30, a higher incidence of Gram-negative bloodstream infections (BSIs) was observed in Cohort B (12% vs. 23%; p=0.05). By day +100 and between days +100 and +180, the incidence of BSIs and of the various etiological agents, the mortality from Gram-negative bacteria, and the incidence of invasive fungal infections were not different in the two Cohorts. The incidence of CMV reactivations by day +100 dropped drastically in patients of Cohort B, following letermovir registration (51% vs. 15%; p=0.00001).DiscussionThe results of this study suggest that the BATMO program is safe. In particular, the choice to avoid prophylaxis with fluoroquinolone was associated with an increase in Gram-negative BSIs by day +30, but this did not translate into higher levels of mortality. Moreover, this strategy was associated with a significant reduction of Clostridiodes difficile infections. The efficacy of anti-CMV prophylaxis with letermovir was confirmed by a significant reduction in CMV reactivations. Even though patients in Cohort B were at higher risk of developing fungal infections (more haploidentical transplants with more myeloablative regimens), the extensive use of posaconazole for prophylaxis balanced this risk, and no increase in the incidence of fungal-associated complications was observed.

#17 Gut decontamination, the microbiome, and the risk of bloodstream infections during pediatric allogeneic hematopoietic cell transplantation

Abstract Background Gut decontamination (GD) is the practice of using antibiotics to eradicate intestinal microbes before and during hematopoietic cell transplantation (HCT). Pre-clinical studies suggest that GD may be protective against acute graft-versus-host-disease (aGVHD), although no studies have focused on the potential impact of GD on non-aGVHD treatment related illnesses. Recently, we completed a randomized controlled trial of GD in pediatric patients. We report the results of an exploratory analysis of the impact of gut decontamination on the incidence of bloodstream infections (BSI) in pediatric HCT patients. Method We conducted a randomized phase 2 trial (ClinicalTrials.gov NCT02641236) of GD in pediatric patients undergoing allo-HCT with the primary objective to characterize the gut microbiota at 2-weeks post-HCT. Patients were randomized to receive the GD regimen (Arm A, n=10) (oral vancomycin-polymyxin B from day -5 through neutrophil engraftment) or not receive GD (no-GD; Arm B, n=10). Serial stool samples were collected from patients in both arms and subsequently underwent shotgun metagenomic sequencing to characterize the gut microbiome. In an exploratory, post-hoc analysis, stool metagenomic sequences were compared against the assembled sequence of a BSI isolate for any patient with a BSI in the first 100 days using a population average nucleotide identity (popANI) metric. Assembled BSI contigs and binned contigs from stool metagenomic sequences were profiled for antibiotic resistance genes (ARGs) with the Comprehensive Antibiotic Resistance Database (CARD) and the Resistance Gene Identifier (RGI) using default parameters. Results There was no statistical difference between the two arms in Shannon diversity of the gut microbiota at 2 weeks post-transplant for either genus (p=0.80) or species level (p=0.44). Six patients had a total of nine BSI episodes in the first 100 days post-HCT. We observed fewer BSI (1 vs. 5, Fig. 1A, p=0.048) in the GD vs no-GD arm, respectively. Using strain-specific analysis of BSI-causing bacteria and temporal association with the stool microbiome from patients who developed BSIs, we identified BSI-causing pathogens in 7 of 9 BSI episodes in the gut microbiome in the no-GD arm (Fig. 1B), including the genus Staphylococcus (Fig. 1C) in 2 patients. The 1 BSI in the GD arm was not derived from the gut (Fig. 1B). The number of unique colistin-, polymyxin B-, and vancomycin-ARGs were similar between the two arms (Fig. 1D). Conclusion Shannon diversity was similar in patients with or without GD, possibly due to the prevalent use of systemic antibiotics in the no-GD arm. Staphylococcus was found in the gut suggesting the need for an expanded definition of non-mucosal barrier injury (MBI) pathogens in HCT. All gut-localized BSIs were found in the non-GD arm suggesting that GD may protect against BSI in HCT patients by decreasing the prevalence or abundance of pathogens that can translocate across the mucosal barrier and subsequently cause gut-derived BSIs.

#20 Bloodstream Infection is Associated with Prior Gut Microbiome Colonization of the Same Strain in the Neonatal Intensive Care Unit

Abstract Background Infants hospitalized in neonatal intensive care units (NICUs) have high incidence of bacterial bloodstream infections (BSIs) leading to up to 15% mortality and substantial morbidity. Common etiologies of BSI in the NICU are pathogens also capable of colonizing the preterm infant gut. However, differentiating susceptible neonates from those in the same environment remains challenging. We hypothesized that the same strains causing BSI increase in abundance in the gut of affected neonates prior to bacteremia and increased above controls in the same environment. Method We performed shotgun metagenomic sequencing on 462 fecal samples from 19 infants with BSI and 37 controls in the same NICUs paired for gestational age, days of life, antibiotic exposure, delivery mode, and sex. We whole genome sequenced the BSI isolate from 19 cases (6 Staphylococcus aureus, 3 Streptococcus agalactiae, 3 Serratia marcescens, 2 Enterococcus faecalis, 2 Klebsiella pneumoniae, 2 Escherichia coli, and 1 Enterobacter cloacae). We utilized MetaPhLan3 to infer taxonomy and InStrain to track the whole genome sequence of the BSI pathogen within the fecal metagenomes longitudinally. We performed generalized linear mixed effect models with MaAsLin2 to determine significant associations between the microbiome and metadata with subject as a random effect. Results We found no differences in gut microbiome diversity or richness between cases and controls relative to bacteremia day of life. However, infants who experience a BSI possess significantly higher median relative abundances of the causative species in their gut relative to paired controls in the 2 weeks prior to bacteremia (Figure 1A, median 21.4% IQR 0.33-52 vs. 0.4% IQR 0.23-10.5, p&amp;lt;0.05 Wilcoxon). 10/19 infants produced at least 1 stool before bacteremia containing an organism with 0-1 genomic substitutions from the BSI isolate, establishing isogenicity between gut residing and invasive pathogen. The coverage (abundance) of the BSI isolate increased in the stool of affected neonates in the 10 days before infection to an average maximum of 0.48/1.0 (Figure 1B, linear mixed effect model p&amp;lt;0.05). We observed the strongest associations between high gut microbiome abundance of E. faecalis, Klebsiella spp., E. coli, and S. marcescens in the gut microbiome of cases whose BSI was caused by that organism compared to all other samples (p&amp;lt;0.01). Conclusion We show high relative abundance of the same strain in stool prior to bacteremia in hospitalized neonates. The relative abundance of the causative species is higher in cases versus paired controls. These data suggest the potential of gut microbial surveillance and management to identify blooms of gut pathogens to limit the incidence of bacteremia.

Escherichia coli sequence type 73 bloodstream infections in a centralized Canadian region and their association with companion animals: an ecological study.

Extraintestinal pathogenic E. coli (ExPEC) are important pathogens causing community-acquired infections in humans, including bloodstream infections (BSIs), and may also colonize and infect animals. Our aim was to investigate associations between incidence rates (IRs) of BSIs caused by ExPEC and number of dogs and cats in communities in Calgary. We used a well-characterized collection of blood isolates (n = 685) from Calgary, Alberta, Canada (2016). We used a combination of a seven-single-nucleotide-polymorphism quantitative PCR to type ExPEC into sequence types (STs). Calgary census data were used to estimate IRs per city community, as well as to investigate associations between number of companion animals per community, as obtained from licensing data, and IR of BSIs caused by each dominant ST. From the 685 isolates available, ExPEC ST131 was most prevalent (21.3% of included isolates), followed by ST73 (13.7%), ST69 (8.2%), ST95 (6.7%), and ST1193 (5.3%), respectively. Incidence of BSIs caused by ExPECs among Calgary residents was 48.8 cases per 100,000 resident-years, whereas communities had on average of 1.7 companion animals per 10 residents. No association between the number of dogs and IR of BSIs caused by ExPECs was detected for any ST. Conversely, the incidence rate of BSIs caused by ST73 was 3.6 times higher (95%CI 1.3-9.99) for every increase of 1 cat per 10 habitants in communities. Number of cats per habitant was positively associated with the incidence of BSIs caused by ExPEC ST73.

Grading bloodstream infection risk using citrulline as a biomarker of intestinal mucositis in patients receiving intensive therapy.

Earlier studies have suggested that severe intestinal mucositis (IM; citrulline < 10 µmol/L) is an independent risk factor for bloodstream infections (BSI) after cytotoxic therapy. Our aim was to grade IM in patients receiving commonly used chemotherapy and conditioning regimens, and characterize its relationship with BSI incidence. In a retrospective analysis of remission induction (RI) chemotherapy, or conditioning for autologous and allogeneic hematopoietic stem cell transplantation (HSCT; myeloablative conditioning [MAC] and non-myeloablative and reduced-intensity conditioning [NMA/RIC]), data were collected on central venous catheter (CVC) characteristics and BSI. The relationship between BSI occurrence and the degree of IM (determined by citrulline levels) and neutropenia was analyzed. In 626 CVC episodes, 268 (42.8%) laboratory-confirmed BSIs (LCBIs) occurred, classified as mucosal barrier injury (MBI)-LCBIs in 179 (28.6%) episodes, central line-associated BSIs in 113 (18.1%) episodes, and catheter-related BSIs in 55 (8.8%) episodes. In NMA/RIC, the mean duration of hypocitrullinemia was 0.77 days, with LCBI and MBI-LCBI occurring in 11.1% and 4.8% of episodes. In autologous HSCT, RI, and MAC allogeneic HSCT, LCBI and MBI-LCBI occurred frequently (40.0-63.8% and 22.8-53.2% of episodes, respectively) and the mean duration of hypocitrullinemia was significantly higher (9.2-13.8 days). There was a strong correlation between LCBI and the duration of hypocitrullinemia (Pearson's correlation coefficient R = 0.96), as opposed to the relationship between LCBI and the duration of neutropenia (R = 0.42). We conclude that citrulline can be used to grade BSI risk for commonly used intensive treatment regimens.

Indwelling Central Venous Catheters Drive Bloodstream Infection During Veno-venous Extracorporeal Membrane Oxygenation Support.

Blood stream infection (BSI) is a potentially lethal complication in patients receiving extracorporeal membrane oxygenation (ECMO). It may be particularly common in patients with veno-venous ECMO due to their long hospitalization in the intensive care unit. Given that these patients have concurrent indwelling central venous catheters (CVC), it is unclear whether the ECMO circuit, CVC, or both, contribute to BSI. This study evaluated the risk factors associated with BSI in patients receiving veno-venous ECMO in a single institution study of 61 patients from 2016 through 2019. All ECMO catheters and the circuit oxygenator fluid were aseptically collected and analyzed for microorganisms at the time of decannulation. New BSI was diagnosed in 15 (24.6%) patients and increased mortality by threefold. None of the ECMO catheters or oxygenator fluid were culture positive. BSI increased with CVC use of over 8 days and was significantly lowered when CVC were exchanged by day 8 compared with patients with exchanges at later points (15.0% vs. 42.8%, p = 0.02). Median length of CVC use in the BSI-negative and BSI-positive group were 6.3 ± 5.0 and 9.4 ± 5.1, respectively (p = 0.04). In summary, BSI is a potentially lethal complication in patients receiving ECMO. Indwelling CVC, not the ECMO circuitry, is the likely contributor for BSI, and exchanging CVC by day 8 can reduce the incidence of BSI.