Laboratory-confirmed Bloodstream Infection Research Articles

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

High Proportion of Mucosal Barrier Injury- Laboratory Confirmed Bloodstream Infection Among Paediatric Oncology Patients in a Cancer Centre in Eastern India

Abstract Introduction Blood stream Infections (BSI) is associated with increased morbidity, mortality, health care costs and healthcare resource utilization. The 2022 version of CDC/NHSN criteria for mucosal barrier injury-associated laboratory-confirmed bloodstream infection (MBI-LCBI-1) included isolation of any intestinal organism from blood culture in a patient with absolute neutrophil count <500/mm3. Children with malignancy have a high risk for infections due to neutropenia, immunosuppressive therapy, individual immune and nutritional status, chemotherapy infusion, radiotherapy, impaired mucosal barrier, and presence of different types of indwelling catheters. CLABSI is defined as an LCBI where an eligible BSI organism is identified, and an eligible central line is present on the LCBI date of event or the day before. Device Utilisation Ratio (DUR) is a ratio comparing the number of device days to the number of patient days for the included time period. Methods A retrospective analysis of all BSI-s in the paediatric unit of a tertiary oncology hospital in a low-middle income country (LMIC) for 43 months (April 2019-October 2022) was performed. The primary objective was to assess the burden of MBI-LCBI-1 in children with cancer. The secondary objective was to assess the CLABSI rate and compare it to the DUR. MBI-LCBI-1, CLABSI and DUR were determined using the standard CDC/NHSN criteria. The adapted CDC/NHSN bloodstream infection case report form included microbiological (type of pathogen) and clinical (signs, symptoms, and underlying conditions such as neutropenia) information. Neutropenia (absolute neutrophil count <500 cells/mm3) was the underlying condition in the MBI-LCBI cases. Blood cultures were done using BACT-ALERT system and antibiotic susceptibility testing performed using VITEK2 system (Biomerieux). Results A total of 47 positive blood cultures were obtained from 46 patients during the study period. Thirty-three cases of MBI-LCBI-1 (33/47= 70%) from 28 patients (median age 14 years; range 4-20 years) and 3 cases of CLABSI (3/47= 6.3%) from 3 patients (median age 7 years; range 3-9 years) were detected giving a CLABSI rate of 0.60 per 1000 central line days. Total Patient days and central line days was 15,002 and 14,764 respectively. The device utilization ratio of central line was 0.98. There were 48 isolates from 47 cases of BSI. Forty-three (90%) were Gram negative bacilli (GNB), 2 (4%) Gram positive cocci (GPC) and 3 (6%) Candida species. Klebsiella pneumoniae (28%) was the commonest GNB. Amongst the multi-drug resistant organisms (MDRO) associated with MBI-LCBI-1, carbapenem-resistant enterobacterales (CRE) was detected in 14/43 (32.5%), carbapenem-resistant Acinetobacter baumanii complex (CRAb) in 1/43 (2.3%), carbapenem-resistant Pseudomonas aeruginosa (CRPseu) in 2/43 (4.7%). Candida auris was detected in 1/3 Candida isolates. Six out of 46 patients with BSI died within 30 days of BSI (all-cause mortality). Four of these patients had CRE, 1 had CRAb and 1 had Candida auris. There were no isolates of Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Conclusion All patients who died had MDRO isolates. Strict adherence to standard and contact precautions, with high level of awareness is necessary for lowering the incidence of BSI. Low incidence of CLABSI is a good indicator of good infection control practices.

Infection Burden and Timing in the First Year After Pediatric Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

Abstract Background Infection is a leading cause of morbidity and non-relapsed mortality (NRM) after allogeneic hematopoietic cell transplant (allo-HCT). This study aimed to describe the contemporary epidemiology of infections, overall survival (OS) as well as NRM at 1 year post pediatric allo-HCT. Methods Retrospective review of laboratory-confirmed infections among patients who underwent first allo-HCT from January 2014 to December 2020 at a single, quaternary pediatric hospital. Cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV) and Human Herpes Virus-6 (HHV-6) weekly viral surveillance was performed on blood using polymerase chain reaction until day +100. We reviewed Clostridioides difficile, bacterial blood stream infections (BSIs), and fungemia until 1 year post allo-HCT or death. Results During the six-year study period, 146 subjects underwent allo-HCT at a median age of 8.75 years (IQR 2.6-14.28), predominantly males (58%) with hematologic malignancies (60%), and bone marrow as stem cell source (71%). Matched unrelated donors were used in 53% after myeloablative conditioning in 62%. A total of 126 patients (86%) experienced at least one infection, primarily with DNA viral infections (n=113, 77%). EBV DNAemia occurred in 50%, CMV in 30%, HHV-6 in 23%, and AdV in 17%. The time to first DNAemia detection post HCT was 15 days for CMV (IQR 6-28.5), 20 days for AdV (IQR 6-89), 22 days for HHV-6 (IQR 17-31), and 55 days for EBV (IQR 41-92.5). Bacterial BSIs were identified in 37% (54/146) of patients at a median of 12.5 days post-HCT (IQR 5-146.3), 80% (43/54) experienced a single episode, while 20% (11/54) had multiple episodes, resulting in 68 BSIs total. Among all BSIs, 38% (26/68) were classified as mucosal barrier injury laboratory confirmed bloodstream infections, while 59% (40/68) as central line associated BSIs. In total, 89 pathogens were identified. Gram-negative pathogens (GN) were predominant in 56% (50/89) of the isolates, with lactose fermenters representing 72% (36/50). Gram-positive pathogens (GP) accounted for 44% (39/89), primarily Staphylococcus species (36%, 14/39, predominantly Staphylococcus aureus in 10 cases) and Viridans Group Streptococcus (31%, 12/39). Clostridioides difficile was detected by PCR in 19% (27/146), with a median onset of 54 days post-HCT (IQR 19-125). Fungemia occurred on 3% (4/146) at a median of 150 days post-HCT (IQR 40.23 - 226.8), 3 had candidemia and 1 had fusariosis. The overall mortality rate at 1 year was 15% (22/146), with a median time from transplant to death of 188 days (IQR 44-233.5) and documented active infection at the time of death in 41% (9/22). Only the presence of fungemia showed a significantly difference in OS (25% vs 87%, p < 0.0001) and NRM (50% vs 5.6%, p < 0.001) Conclusions Infections occurred frequently in our cohort affecting 86% (126/146), most commonly as viral DNAemia [77% (113/146)] with EBV > CMV > HHV-6 > AdV, followed by bacterial BSI [37% (54/146)] with GN (56%) vs GP (44%). Despite CLABSI prevention efforts, CLABSI occurred 40 (59%) of total bacterial BSI episodes. Despite the higher frequency of bacterial and viral infections, only fungemia was significantly associated with decreased OS and higher NRM.

Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.

We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania. We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use. Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each). Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study

Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. Bill & Melinda Gates Foundation.

Validation of automated surveillance of healthcare-associated infections using electronic screening algorithms

Background: Surveillance of healthcare-associated infection (HAI) is the basis of infection prevention programs. However, manual review of medical records is a labor-intensive and time-consuming process. We evaluated the diagnostic performance of automated surveillance of HAI using electronic screening algorithms. Methods: Between April and June 2022, we conducted surveillance of HAI manually and automatically using electronic screening algorithm on 75 units (general medical and surgical wards and ICUs) in a 2,700-bed, tertiary-care hospital in South Korea. Algorithms for surveillance of HAI were developed accordance with NHSN surveillance definitions (Fig. 1). Catheter-associated urinary tract infections (CAUTIs) were automatically detected when eligible pathogen and fever (>38°C) were matched within infection window period. Other specific types of infection were automatically classified based on laboratory results that met NHSN criteria. After the algorithm showed possible cases that met laboratory-confirmed bloodstream infection (LCBI) criteria, we excluded secondary BSIs using the automatic surveillance algorithm. We analyzed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the automated surveillance system compared to manual surveillance. Results: An algorithm for detecting CAUTI showed 98.7% sensitivity (78 of 79), 100.0% specificity (2,443 of 2,443), 100.0% PPV (78 of 78), and 100.0% NPV (2,443 of 2,444). For CLABSI, the algorithm had 97.3% sensitivity (214 of 220), 98.3% specificity (5,759 of 5,861), 67.7% PPV (214 of 316), and 99.9% NPV (5,759 of 5,765). In total, 102 cases of possible CLABSI were identified by the algorithm, and 76 (74.5%) were eventually diagnosed as secondary BSIs. Also, by chart review, 20 BSIs (19.6%) were present on arrival in ER (ER-POA). In 4 cases (3.9%), an original pathogen reoccurred in a repeated infection timeframe (RIT), and 2 cases (2%) were mucosal barrier injury-LCBI (MBI-LCBI). When we additionally performed manual surveillance for intra-abdominal infection secondary BSI, ER-POA, and assigning pathogen to original BSI in RIT, PPV increased to 87.7% (214 of 244). Conclusions: Algorithm for automated surveillance of CAUTI had good performance; however, automated surveillance of CLABSI was suboptimal. More elaborate screening algorithm for diagnosis CLABSI is needed, and further studies are needed to determine whether an automated surveillance system can reduce workload for surveillance of HAI.Disclosures: None

Bloodstream Infections in Infants and Children With Congenital Heart Disease Undergoing Cardiac Surgery

Children with congenital heart disease undergoing cardiac surgery are at risk for laboratory-confirmed bloodstream infections (LCBIs). These infections can lead to morbidity, mortality, and increased health care costs. The role of mucosal barrier injury in causing LCBIs is unknown. To describe characteristics of LCBIs in patients admitted to cardiac intensive care and step-down units and to assess frequencies of National Healthcare Safety Network infection types and associations with organism classification, patient clinical factors, and infection outcomes. A retrospective cohort analysis using manual electronic medical record data abstraction included children with congenital heart disease who developed an LCBI while receiving inpatient cardiac care between August 2011 and November 2018 at one institution. Demographic, clinical, laboratory, and outcome variables were collected and analyzed with descriptive and inferential statistics. Eighty-seven patients with congenital heart disease developed 103 LCBIs during the study time frame. The most common causative microorganisms were gram-positive bacteria, including Enterococcus faecalis and Staphylococcus epidermidis. Sixty-three percent of causative organisms were characterized as originating from mucosal barrier injury, although no infections met National Healthcare Safety Network criteria for mucosal barrier injury LCBIs. Translocation of bacteria through injured gut mucosa may cause bloodstream infections in children with congenital heart disease. Further investigation is warranted to understand microbiome changes that adversely select pathogenic gut organisms. Preventive care to maintain intact gut function and a healthy microbiome should be explored for this patient population.

Comparison between the time to detection of pathogenic and nonpathogenic microorganisms from blood culture specimens using the BACTECTM FX machine to determine the optimal incubation time

Introduction: Bloodstream infections can lead to a high rate of life-threatening sepsis, morbidity and mortality, requiring early and accurate detection. The gold standard for diagnosing bacteremia is blood culture. The recommended incubation time of blood cultures is five days minimum, but studies have shown that five-day incubation is unnecessary. This study aims to determine the optimal blood incubation time on the BACTECTM FX machine. Methods: This is an analytic observational study with a cross-sectional retrospective approach. The samples resulted from tests in the Clinical Microbiology Laboratory and medical record data of patients at Dr. Soetomo Regional Public Hospital, Surabaya, with suspected bacteremia and fungemia-positive blood cultures based on tests with the BACTECTM FX machine who met the inclusion criteria. Samples were analyzed for Time to Detection (TTD) and identification results. TTD of 96–120 hours was analyzed to assess the occurrence of Laboratory-Confirmed Bloodstream Infection (LCBI). Results: From a total of 2,221 samples, 875 (39.4%) pathogenic microorganisms and 1,346 (60.6%) nonpathogenic microorganisms were identified. At TTD < 24 hours, the number of pathogenic microorganisms was higher, reaching 86.6%, than that of nonpathogenic microorganisms, reaching 68.8%. Whereas at TTD of 24–< 48 hours, nonpathogenic microorganisms had a higher count, reaching 23.1%, than pathogenic microorganisms, reaching 10.1%. A total of 2,203 (99.2%) microorganisms were identified at TTD < 96 hours, and as many as 18 (0.8%) microorganisms with TTD > 96 hours. Conclusion: There is no difference in the distribution of pathogenic and nonpathogenic microorganisms at TTD < 96 hours and TTD 96–120 hours. Based on tests using the BACTECTM FX machine, five LCBI-group microorganisms based on NHSN criteria were found with TTD of 96–120 hours, namely Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Trichosporon asahi, and coagulase-negative Staphylococcus, and thirteen non-LCBI-group microorganisms were identified.

Multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteraemia rates among cancer patients in an oncology hospital in eastern India: an 11-year retrospective observational study

Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India. To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India. A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously. 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli (E.coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients. This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians.

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 < 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< 0.001) and no removal of central lines after previous episode (OR, 51.143; 95% CI, 6.6-395.0; P< 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.

2014. Central Line - Associated Bloodstream Infections and Their Increase With the COVID-19 Pandemic at Veterans Affairs in San Antonio, Texas

Abstract Background Coronavirus disease-19 (COVID-19) has been associated with an increase in healthcare-associated infections (HAI). This increase is likely multifactorial (i.e. higher hospitalization rates, COVID-19 and post-COVID-19 complications, lower staffing, delayed care among others). The objective of this study was to determine the association between COVID-19 hospitalization rates and central line- associated blood stream infections (CLABSI). Methods We conducted a retrospective study in acute care unit hospitalizations in a Veterans Affairs (VA) hospital in San Antonio, Texas from October 2017 to December 2021. Individuals over 18 years of age admitted with a new diagnosis of COVID-19, determined by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) were included in the study. CLABSIs were defined by the National Healthcare Safety Network (NHSN) criteria for laboratory confirmed bloodstream infections. Pearson correlation was used to determine correlation of CLABSI and COVID-19 disease hospitalization rates. CLABSI rates were also compared pre-COVID-19 (Oct 2017-Feb 2020) to COVID-19 (Mar 2020-Dec 2021) periods using the chi-square test. Results During the study period, a total of 0.69 CLABSIs per 1,000 central line days occurred in the pre-COVID-19 period compared to 1.98 per 1,000 in the COVID-19 period (p=0.004). There was a significant correlation between CLABSI and ICU COVID-19 hospitalization rates (R=0.459; p=0.001) as well as CLABSI and acute care COVID-19 hospitalization rates (R=0.341; p=0.014). During the COVID-19 period only, there continued to be a significant correlation between CLABSI and COVID-19 ICU hospitalization rates (R=0.426; p=0.048). Conclusion CLABSI rates significantly increased during the COVID-19 period compared to the pre-COVID-19 period and CLABSI rates were significantly correlated with COVID-19 ICU and acute care hospitalizations. Accounting for this variable allows us to factor in impact of post-COVID-19 related complications and association with CLABSI rate. We urge for careful implementation of HAI prevention strategies during the pandemic. Awareness of anticipated increase is important in allocating resources essential for prevention of HAIs. Disclosures All Authors: No reported disclosures.

Antimicrobial Resistance of Enterobacteriaceae in Bloodstream Infections in Hospitalized Patients in Southern Poland

Aim: The aim of this study was to highlight antimicrobial resistance among Enterobacteriaceae isolated from bloodstream infections in hospitals in southern Poland. Materials and Methods: The present study includes laboratory-confirmed secondary bloodstream infections (LC-BSIs), in the years 2015–2018, in hospitalized adult patients (≥18). Episodes of BSIs were defined according to the strictly described guidelines. Antimicrobial susceptibility testing was performed with the automated system and the disc diffusion method. Extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriaceae were detected using the double-disc synergy test. Results: Between 2015 and 2018, 356 episodes of secondary BSIs in 997 patients aged 21–96 years were documented in a prospective study, including 134 (37.6%) ESBL-producing Enterobacteriaceae. Escherichia coli was the predominant pathogen in internal medicine (37.6%) and surgery units (46.8%); in intensive care units (ICUs), Klebsiella pneumoniae was isolated more frequently (33.3%). Enterobacteriaceae were highly resistant to most antimicrobial agents. K. pneumoniae isolates had a higher level of resistance than E. coli, regardless of the unit. Conclusions: The increase in AMR and the widespread distribution of ESBL-producing Enterobacteriaceae in Polish hospitals can be related to the lack of or inappropriate antibiotic treatment.

Selective National Healthcare Safety Network Central Line-Associated Bloodstream Infection Validation in State Health Department, Jan – June 2018

Background Accurate reporting to the National Healthcare Safety Network (NHSN) is critical in providing actionable surveillance data to inform infection prevention (IP) programs. The state health department (SHD) validated Central Line-Associated Bloodstream Infections (CLABSI) to assess data accuracy and identify common reporting errors. Methods Utilizing the NHSN external validation toolkit, the SHD validated 21 facilities based on data reported from Intensive Care Units (ICU) and Medical, Surgical, and Medical/Surgical Ward locations during January to June 2018. Nine facilities were selected for both ICU and Ward locations, 6 for ICU only and 6 for Ward only. For each facility, up to 20 reported NHSN CLABSI events and up to 40 unreported or candidate events were reviewed. Patient medical records were reviewed to determine if the selected blood culture met CLABSI event criteria. Results The SHD reviewed a total of 1112 medical records. The SHD identified 120 reportable CLABSI events; of these, 7/120 (6%) were reported with errors and 10/120 (8%) were not reported at all. Additionally, the SHD found two reported events that were deemed Secondary Bloodstream Infections (BSI); therefore, did not meet primary CLABSI criteria and were subsequently over-reported. The overall sensitivity was 92% and specificity was 99.8%. Facility specific sensitivities ranged from 71% to 100%. Conclusions The majority of unreported CLABSI events were due to misattribution of the event as a Secondary BSI. In these instances, along with the over-reported events, facilities most often incorrectly applied the site-specific criteria for pneumonia. Of the seven events that were reported incorrectly, the most common reporting errors were incorrect location due to the transfer rule and incorrect event date, specifically when the symptom occurred before the culture date when applying Laboratory-Confirmed Bloodstream Infection (LCBI) criteria 2. The SHD will use these results to tailor NHSN training and education to facilities. Accurate reporting to the National Healthcare Safety Network (NHSN) is critical in providing actionable surveillance data to inform infection prevention (IP) programs. The state health department (SHD) validated Central Line-Associated Bloodstream Infections (CLABSI) to assess data accuracy and identify common reporting errors. Utilizing the NHSN external validation toolkit, the SHD validated 21 facilities based on data reported from Intensive Care Units (ICU) and Medical, Surgical, and Medical/Surgical Ward locations during January to June 2018. Nine facilities were selected for both ICU and Ward locations, 6 for ICU only and 6 for Ward only. For each facility, up to 20 reported NHSN CLABSI events and up to 40 unreported or candidate events were reviewed. Patient medical records were reviewed to determine if the selected blood culture met CLABSI event criteria. The SHD reviewed a total of 1112 medical records. The SHD identified 120 reportable CLABSI events; of these, 7/120 (6%) were reported with errors and 10/120 (8%) were not reported at all. Additionally, the SHD found two reported events that were deemed Secondary Bloodstream Infections (BSI); therefore, did not meet primary CLABSI criteria and were subsequently over-reported. The overall sensitivity was 92% and specificity was 99.8%. Facility specific sensitivities ranged from 71% to 100%. The majority of unreported CLABSI events were due to misattribution of the event as a Secondary BSI. In these instances, along with the over-reported events, facilities most often incorrectly applied the site-specific criteria for pneumonia. Of the seven events that were reported incorrectly, the most common reporting errors were incorrect location due to the transfer rule and incorrect event date, specifically when the symptom occurred before the culture date when applying Laboratory-Confirmed Bloodstream Infection (LCBI) criteria 2. The SHD will use these results to tailor NHSN training and education to facilities.

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.

Plasma cfDNA predictors of established bacteraemic infection.

Introduction. Increased plasma cell-free DNA (cfDNA) has been reported for various diseases in which cell death and tissue/organ damage contribute to pathogenesis, including sepsis. Gap Statement. While several studies report a rise in plasma cfDNA in bacteraemia and sepsis, the main source of cfDNA has not been identified. Aim. In this study, we wanted to determine which of nuclear, mitochondrial or bacterial cfDNA is the major contributor to raised plasma cfDNA in hospital subjects with bloodstream infections and could therefore serve as a predictor of bacteraemic disease severity. Methodology. The total plasma concentration of double-stranded cfDNA was determined using a fluorometric assay. The presence of bacterial DNA was identified by PCR and DNA sequencing. The copy numbers of human genes, nuclear β globin and mitochondrial MTATP8, were determined by droplet digital PCR. The presence, size and concentration of apoptotic DNA from human cells were established using lab-on-a-chip technology. Results. We observed a significant difference in total plasma cfDNA from a median of 75 ng ml−1 in hospitalised subjects without bacteraemia to a median of 370 ng ml−1 (P=0.0003) in bacteraemic subjects. The copy numbers of nuclear DNA in bacteraemic also differed between a median of 1.6 copies µl−1 and 7.3 copies µl−1 (P=0.0004), respectively. In contrast, increased mitochondrial cfDNA was not specific for bacteraemic subjects, as shown by median values of 58 copies µl−1 in bacteraemic subjects, 55 copies µl−1 in other hospitalised subjects and 5.4 copies µl−1 in healthy controls. Apoptotic nucleosomal cfDNA was detected only in a subpopulation of bacteraemic subjects with documented comorbidities, consistent with elevated plasma C-reactive protein (CRP) levels in these subjects. No bacterial cfDNA was reliably detected by PCR in plasma of bacteraemic subjects over the course of infection with several bacterial pathogens. Conclusions. Our data revealed distinctive plasma cfDNA signatures in different groups of hospital subjects. The total cfDNA was significantly increased in hospital subjects with laboratory-confirmed bloodstream infections comprising nuclear and apoptotic, but not mitochondrial or bacterial cfDNAs. The apoptotic cfDNA, potentially derived from blood cells, predicted established bacteraemia. These findings deserve further investigation in different hospital settings, where cfDNA measurement could provide simple and quantifiable parameters for monitoring a disease progression.

Errors in Antimicrobial Prescription and Administration in Very Low Birth Weight Neonates at a Tertiary South African Hospital.

BackgroundAntimicrobial prescription and administration-related errors occur frequently in very low birth weight (VLBW; <1,500 g) neonates treated for bloodstream infections (BSI).MethodsAntimicrobial prescriptions for the treatment of laboratory-confirmed BSI were retrospectively analyzed for VLBW neonates at Tygerberg Hospital, Cape Town, South Africa (1 July 2018 - 31 December 2019), describing antimicrobial type, indication, duration of therapy and BSI outcomes. The prevalence of, and risk factors for prescription (dose, interval) and administration errors (hang-time, delayed/missed doses) were determined.ResultsOne hundred and sixty-one BSI episodes [16 (9.9%)] early-onset, 145 [90.1%] healthcare-associated) affected 141 neonates (55% male, 25% born to mothers living with HIV, 46% <1,000 g birth weight) with 525 antimicrobial prescription episodes [median 3.0 (IQR 2–4) prescriptions/BSI episode]. The median duration of therapy for primary BSI, BSI-associated with meningitis and BSI-associated with surgical infections was 9, 22, and 28 days, respectively. The prevalence of dose and dosing interval errors was 15.6% (77/495) and 16.4% (81/495), respectively with prescription errors occurring most commonly for piperacillin-tazobactam and vancomycin given empirically. Administration errors were less frequent [3.8% (219/5,770) doses missed; 1.4% (78/5,770) delayed], however 64% had a hang-time (time from sepsis diagnosis to 1st dose of antimicrobial) exceeding 60 min. On multivariable analysis, postnatal age >7 days was associated with prescription errors (p = 0.028). The majority of neonates with BSI required escalation of respiratory support (52%) and 26% required intensive care admission. Despite fair concordance between empiric antimicrobial/s prescription and pathogen susceptibility (74.5%), BSI-attributable mortality in this cohort was 30.4%.ConclusionVLBW neonates with BSI's were critically ill and had high mortality rates. Hang-time to first antimicrobial administration was delayed in two-thirds of BSI episodes and prescription errors affected almost 1 in 6 prescriptions. Targets for intervention should include reducing hang-time, use of standardized antimicrobial dosing guidelines and implementation of antimicrobial stewardship recommendations.

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.

The Impact of Interventions to Prevent Neonatal Healthcare-associated Infections in Low- and Middle-income Countries: A Systematic Review.

Background:Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown.Aim:To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units.Methods:Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units.Results:Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-intervention studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections.Conclusions:There is a limited evidence base for the effectiveness of infection prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection prevention and control intervention strategies in low-resource neonatal units.

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.

Bloodstream infections in hospitalized patients before and during the COVID-19 surge in a community hospital in the South Bronx

Bloodstream infections in hospitalized patients before and during the COVID-19 surge in a community hospital in the South Bronx