scholarly journals 1576. Re-Evaluation of cefepime or piperacillin-tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales BloodStream Infections (REDUCE-BSI)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S786-S787
Author(s):  
Catherine H Vu ◽  
Veena Venugopalan ◽  
Barbara A Santevecchi ◽  
Stacy A Voils ◽  
Kartikeya Cherabuddi ◽  
...  

Abstract Background The ideal therapy for treatment of bloodstream infections (BSI) due to ESBL-producing organisms is widely debated. Although prior studies have demonstrated efficacy of non-carbapenems (CBPNs) for ESBL infections, results from the MERINO study group found increased mortality associated with piperacillin/tazobactam (PT) when compared with meropenem for treatment of ESBL BSI. The goal of this study was to investigate patient outcomes associated with the use of CBPN-sparing therapies (PT and cefepime (CEF)) for ESBL BSI. The primary outcome was in-hospital mortality between non-CBPN (PT and CEF) and CBPN groups. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and development of resistance. Methods This was a retrospective observational study of patients admitted to the hospital from May 2016 - May 2019 with a positive blood culture for an ESBL-producing organism. Patients receiving meropenem, ertapenem, PT, or CEF were included. Patients were excluded if < 18 years old, receiving antibiotics for < 24 hours, treated for a polymicrobial BSI, or receiving concomitant antibiotic therapy for another gram-negative (non-ESBL) infection. Results One hundred and fourteen patients were analyzed; 74 (65%) patients received CBPN therapy compared with 40 (35%) patients that received a non-CBPN (CEF N=30, PT N=10). There were no statistically significant differences in baseline characteristics between groups. The overall in-hospital mortality rate was 6% (N=7). Eight percent of patients (N=6) in the CBPN arm died compared to 3% (N=1) of patients in the non-CBPN arm, P = 0.42. No difference in mortality was detected between groups when evaluating subgroups with Pitt bacteremia score ≥4 (N=25), requiring ICU admission (N=50), non-genitourinary source (N=50), or by causative organism (N=76 E. coli; N=38 Klebsiella spp.). There was no difference between groups for secondary outcomes. Conclusion CEF and PT are reasonable options for the treatment of ESBL BSI and did not result in increased mortality or decreased clinical efficacy when compared to CBPNs in this cohort. Disclosures All Authors: No reported disclosures

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S6-S7
Author(s):  
Christopher Jackson ◽  
Sarah Bandy ◽  
Will Godinez ◽  
Gerard Gawrys ◽  
Grace Lee

Abstract Background Vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs) are associated with high morbidity and mortality. PCR-based rapid diagnostic tests provide prompt identification of infectious etiologies within hours. This study evaluated the impact of the Verigene® Gram-positive blood culture (GP-BC) panel on the outcomes on patients with VRE BSIs. Methods A multi-center pre- and post-implementation retrospective cohort study was conducted at four large HCA Healthcare facilities. The implementation of Verigene® GP-BC and VigiLanz® surveillance software with real-time notifications to clinical pharmacists occurred in 2015. Adults > 18 years with VRE BSIs were evaluated over two time periods; pre-implementation (Pre; May 2011 - May 2013) and post-implementation (Post; May 2015 - May 2017). Patients were excluded if not admitted or were discharged/deceased before blood culture results. The primary outcome of this study was to compare time to optimal therapy (TOT). Secondary outcomes included hospital mortality, length of stay (LOS), and TOT comparing clinical pharmacy staffing models. Multivariable logistic regression models were used to identify independent predictors. Adjusted ORs (aOR) and their 95% CIs were reported. Results A total of 104 patients with VRE BSIs were included in the study; 50 and 54 in the pre- and post-implementation periods, respectively. There were no differences in baseline characteristics between the groups. TOT was significantly shorter in the post vs. pre group (29 hrs ± 36 vs. 67 hrs ± 124, p=0.03). There was significantly lower hospital mortality when comparing the pre- and post-implementation periods (32% vs. 11%, p< 0.01). After adjusting for age, sex, severity of illness, treatment/dose, the post implementation period was independently associated with reduced hospital mortality (aOR 0.21, CI 0.61–0.73, p=0.01). There were no significant differences in LOS or clinical pharmacy staffing models on TOT. Baseline Characteristics Primary and secondary outcomes data Conclusion The implementation of the Verigene® BC-GP with VigiLanz® substantially decreased TOT for VRE BSIs and was associated with reduced hospital mortality. This study highlights the positive impact of RDTs on shorter TOT and associated clinical outcomes. Disclosures All Authors: No reported disclosures


2013 ◽  
Vol 37 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Afsana Fatema Noor ◽  
Fariza Shams ◽  
Saurab Kishore Munshi ◽  
Munir Hassan ◽  
Rashed Noor

Urinary tract infection (UTI) is increasingly rising in Bangladesh due to the development of resistance of causative pathogens against commonly prescribed antibiotics. Present study attempted to examine the prevalence of such uropathogens and their antibiogram profiles. Among 462 urine samples collected from patients with UTI, 100 were found to be culture positive. Escherichia coli (70%) was predominating, while Klebsiella spp. (11%) and Enterococcus spp. (6%) were also prevalent. About 96% uropathogens were sensitive against imipenem, and 75% against amikacin. The resistance rate of E. coli and Klebsiella spp. against ampicillin was 98.5 and 100%, respectively, and to cefotaxime, 84.3 and 72.8%, respectively. More than 80% resistance against these antibiotics was scored for other isolates. The frequency of drug resistance was found to be comparatively elevated in E. coli, Pseudomonas spp. and Proteus spp. Overall, the present investigation emphasized the need for routine screening of antibiotic resistance to promote effective medication against UTI. DOI: http://dx.doi.org/10.3329/jbas.v37i1.15681 Journal of Bangladesh Academy of Sciences, Vol. 37, No. 1, 57-63, 2013


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S785-S785
Author(s):  
Shawn H MacVane ◽  
Amira A Bhalodi ◽  
Kyle Spafford ◽  
Romney Humphries ◽  
Niels Oppermann

Abstract Background Definitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial. Methods The Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated. Results There were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p> Conclusion In this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp. Disclosures All authors: No reported disclosures.


2021 ◽  
Author(s):  
Samuel Lipworth ◽  
Karina-Doris Vihta ◽  
Timothy Davies ◽  
Sarah Wright ◽  
Merline Tabirao ◽  
...  

Background: Gram-negative organisms are common causes of bloodstream infection during the neonatal period and early childhood with high morbidity and mortality as well as increasing concern about associated antimicrobial resistance. Whilst several large sequencing studies have permitted detailed analysis of the population structure of these isolates in adults, equivalent data is lacking in the paediatric population. Methods: We performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children under the age of 18 between 2008 and 2018 in Oxfordshire, UK. Findings: 327 isolates (of which 296 were successfully sequenced) from 287 patients were included in the study. The burden of infection in the paediatric population lies predominantly in neonates. Most infections were caused by E. coli/Klebsiella spp. and Enterobacter hormaechei. There was no evidence of an increasing incidence of E. coli bloodstream infections and for Klebsiella spp. there was some evidence that the incidence decreased slightly. Similarly the proportion of resistant isolates did not change over time, though we did identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of E. coli isolates causing bloodstream infection in neonates and children mirrors that seen in adults. In most cases there was no evidence of transmission between patients/point source acquisition and whole genome sequencing was able to refute a previously suspected outbreak. Conclusion: Our findings support continued use of current empirical treatment guidelines and likely highlight the success of infection control measures in this population. Our data suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis, potentially by vaccination of pregnant women. Clinical trials to further investigate this possibility are warranted.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3471-3471 ◽  
Author(s):  
Ang Li ◽  
Robert S Makar ◽  
Shelley Hurwitz ◽  
Lynne Uhl ◽  
Richard M. Kaufman ◽  
...  

Abstract Introduction: Thrombotic microangiopathies (TMA) are a group of uncommon disorders characterized clinically by the presence of thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Therapeutic plasma exchange (TPE) is a proven treatment for cases of autoimmune thrombotic thrombocytopenic purpura (TTP) characterized by an ADAMTS13 activity level of ≤10%, but the efficacy of TPE in TMA with an ADAMTS13 activity level of >10% remains controversial. Methods: We conducted a retrospective cohort study of 186 adult patients included in the Harvard TMA Research Collaborative registry who presented with MAHA and thrombocytopenia concerning for TTP but an ADAMTS13 activity level of >10%. A propensity score (PS) logistic regression model was constructed based on 11 clinically relevant confounding variables: age; sex; ethnicity; Charlson Comorbidity Index (CCI); history of prior solid organ or bone marrow transplant; the presence of neurologic symptoms; the presence of sepsis, shock, or multiorgan failure (MOF); platelet count; creatinine; LDH; and INR. Matching was performed using a 1:1 nearest neighbor method without replacement within a set caliper distance. Standardized differences were used to assess the quality of matching and ensure balance of baseline characteristics. The primary outcome was 90-day survival. Secondary outcomes included in-hospital mortality, percent of patients experiencing platelet count recovery, time to platelet count recovery, and hospital length of stay (LOS). Results: Prior to matching, patients treated with TPE (N=71) had a lower acuity of illness compared to untreated patients (N=115) as reflected by a lower mean CCI (2.3 vs. 3.4, P = 0.003), lower mean INR (1.1 vs. 1.3, P = 0.02), and lower incidence of sepsis, shock or MOF (23% vs. 36%, P = 0.06). Consistent with this confounding, TPE in the pre-matched cohort appeared to be associated with reduced mortality at 90 days (HR 0.51, P = 0.01). The PS match was performed to address these imbalances and resulted in 59 TPE-treated patients paired to 59 untreated controls. After matching, baseline characteristics of the treated and untreated groups were well balanced, with a standardized difference of ≤11% in all PS variables (see Figure). In contrast to the unmatched cohort, Cox regression analysis stratified by matched pairs showed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (HR 0.88, 95% CI 0.44-1.8, P = 0.72) (see Table). We performed subgroup analyses by age, diagnostic category, and ADAMTS13 activity level and again did not observe any benefit to TPE. With regard to secondary outcomes, in-hospital mortality (OR 0.77, P = 0.53), percent of patients with platelet count recovery (OR 1.6, P = 0.21), median time to platelet count recovery (6 vs. 6 days, P = 0.99), and median hospital LOS (14 vs. 18 days, P = 0.93) did not differ significantly between the two groups. Conclusions: In the absence of a randomized controlled trial, PS matching represents a rigorous statistical approach to study the effect of treatment while adjusting for differences in baseline characteristics across groups of patients. Here we have used PS matching to assess the efficacy of TPE in the management of TMA associated with an ADAMTS13 activity level of >10%. Our data indicate that there is no benefit from TPE for this diverse group of TMA patients without severe ADAMTS13 deficiency. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S71-S72
Author(s):  
Ashlan Kunz Coyne ◽  
Anthony Casapao ◽  
Carmen Isache ◽  
James Morales ◽  
Yvette McCarter ◽  
...  

Abstract Background Molecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP). Methods Multicenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results. Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates. Results A total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p&lt; 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p&lt; 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups. Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups Graph 1. Kaplan Meier time to optimal antimicrobial therapy Graph 2. Kaplan Meier time to microbial clearance Conclusion Our study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP. Disclosures All Authors: No reported disclosures


2015 ◽  
Vol 64 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Agnieszka Chmielarczyk ◽  
Monika Pobiega ◽  
Jadwiga Wojkowska-Mach ◽  
Dorota Romaniszyn ◽  
Piotr B. Heczko ◽  
...  

Bloodstream infections (BSIs) are associated with a significantly increased risk of fatality. No report has been found about the molecular epidemiology of Enterobacteriaceae causing BSI in neonates in Poland. The aim of this work was to determine the antibiotic resistance profiles, virulence gene prevalence, the epidemiological and genetic relationships among the isolates from Enterobacteriaceae causing BSI in neonates with birth weight < 1501 g. Antimicrobial susceptibility testing was performed. PCR was performed to identify the presence of common beta-lactamase genes, virulence genes. PFGE and MLST were performed. The surveillance group contained 1,695 newborns. The incidence rate for BSIs was 5.9%, the fatality rate 15%. The most common species were Escherichia coli (n = 24) and Klebsiella pneumoniae (n = 16). CTX-M-15 was found in 6 E. coli, 8 K. pneumoniae, 1 Enterobacter cloacae strains. Among E. coli fimH (83.3%), ibeA (37.5%), neuC (20.8%) were the most frequent. PFGE demonstrated unique pulsotypes among E. coli. E. coli ST131 clone was found in 7 E. coli strains. PFGE of 16 K. pneumoniae strains showed 8 pulsotypes. Five isolates from one NICU belonged to one clone. MLST typing revealed 7 different ST with ST336 as the most prevalent. This study provides information about resistance, virulence and typing of Enterobacteriaceae strains causing BSI among neonates. E. coli and Klebsiella spp. isolated in this study have completely different epidemiology from each other.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S703-S703
Author(s):  
Brian E Frescas ◽  
Christopher McCoy ◽  
James Kirby ◽  
Robert Bowden ◽  
Nicholas J Mercuro

Abstract Background Cefepime is a 4th generation cephalosporin frequently used for empiric sepsis therapy. Dose- and MIC-dependent efficacy of cefepime is supported by the Clinical & Laboratory Standards Institute, however its use in infections due to extended-spectrum beta-lactamase-producing Enterobacterales is controversial. This study aims to compare outcomes in patients given empiric meropenem or cefepime for bloodstream infections (BSI) caused by ceftriaxone-resistant E. coli and K. pneumoniae. Methods This single-center retrospective cohort included adults hospitalized from 2010 - 2020 and received empiric cefepime or meropenem for BSI caused by ceftriaxone-resistant E. coli or K. pneumoniae. In the cefepime group, only organisms with MIC ≤ 2 mg/L were included. Patients who received the empiric agent for &lt; 48 hours, or received an additional active agent within 48 hours were excluded. The primary outcome was 30-day mortality; secondary outcomes were recurrent infection, readmission, and time to clinical stability. Chi-squared or Fisher’s exact was used for categorical variables and Mann-Whitney-U for continuous variables. Inverse probability treatment weighing was used to determine the impact of empirical therapy on clinical stability at 48 hours. Results Fifty-four patients were included: 36 received empiric meropenem, 18 received cefepime. There were no significant differences in baseline severity of illness or comorbid conditions. Urinary source was less common in the meropenem group compared to cefepime (52.8 vs 83.8%, p=0.028) (Table 1). There was no difference in 30-day mortality between meropenem and cefepime (2.8 vs 11.1%, p = 0.255). More patients achieved clinical stability at 48 hours on empiric meropenem compared to cefepime (75 vs 44.4%, p = 0.027), and time to clinical stability was significantly shorter (median 21.3 vs 38.5 hours, p = 0.016). Most patients in the meropenem and cefepime groups completed definitive treatment with a carbapenem (88.9 vs 72.2%, p=0.142). Table 1: Results Summary of primary and secondary outcomes Conclusion There was no difference in mortality between patients receiving empiric cefepime for BSI due to ceftriaxone-resistant Enterobacterales, with cefepime MIC ≤ 2 mg/L, compared to meropenem; however, time to clinical stability was significantly delayed. Disclosures James Kirby, MD, D(ABMM), First Light Biosciences (Board Member)TECAN, Inc. (Research Grant or Support)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S152-S153
Author(s):  
William P DePasquale ◽  
Mary L Staicu ◽  
Sean Stainton ◽  
Maryrose R Laguio-Vila ◽  
Mindee Hite ◽  
...  

Abstract Background Traditional methods in blood culture analysis require 24-72 hours to yield identification (ID) and antimicrobial susceptibility testing (AST) results, which may contribute to the use of empiric broad-spectrum antibiotic therapy. Hence, the primary objective of this study was to determine the impact of rapid blood culture analysis with the Accelerate Pheno™ system (AXDX) on time to antibiotic de-escalation. Methods This was a single center, case-control analysis of adult inpatients with E. coli or Klebsiella spp. bacteremia. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 after the implementation of AXDX in July 2020. Subjects were matched to historical controls (July 2018-July 2020) based on age (± 3 years), gender, source of infection, and identified organism. The primary outcome was time to antibiotic de-escalation and time to oral antibiotic therapy from the time of positive blood cultures. Secondary outcomes included hospital length of stay, 30-day mortality, 30-day readmission, and 60-day C. difficile infection. Outcomes were compared using descriptive and inferential statistics. Results Of 33 cases identified, 30 (91%) were matched with historical controls. E. coli bloodstream infection was identified in 24 (80%) subjects while Klebsiella spp. was identified in 6 (20%) subjects. The average age was 66 years (SD ± 19) and there was an even distribution of males and females in both groups. Other demographics were similar between groups. The median time to species identification [14 hours (IQR 13 – 18) vs 34 hours (29 – 39), p&lt; 0.001) and AST [20 hours (19 – 37) vs 45 hours (38 – 51), p&lt; 0.001] from laboratory registration was significantly shorter in cases. The average time to antibiotic de-escalation was 1.7 (±1.2) days for cases compared to 2 (±1.3) days for controls (p=0.460). Median time to oral antibiotic therapy from positive blood cultures was 2.9 (1.8 – 4.7) days for cases and 3.4 (2.5 – 5.1) days for controls (p=0.166). There were no significant differences in the secondary outcomes. Conclusion AXDX did not appear to have a significant impact on time to antibiotic de-escalation and time to oral antibiotic therapy. However, time to organism ID and AST results were significantly shorter in the AXDX cohort. Disclosures All Authors: No reported disclosures


2019 ◽  
Vol 70 (5) ◽  
pp. 1778-1783
Author(s):  
Andreea-Loredana Golli ◽  
Floarea Mimi Nitu ◽  
Maria Balasoiu ◽  
Marina Alina Lungu ◽  
Cristiana Cerasella Dragomirescu ◽  
...  

To determine the resistance pattern of bacterial pathogens involved in infections of the patients aged between 18-64 years, admitted in a ICU from a 1518-bed university-affiliated hospital. A retrospective study of bacterial pathogens was carried out on 351 patients aged between 18-64 years admitted to the ICU, from January to December 2017. In this study there were analysed 469 samples from 351 patients (18-64 years). A total of 566 bacterial isolates were obtained, of which 120 strains of Klebsiella spp. (35.39%%), followed by Nonfermenting Gram negative bacilli, other than Pseudomonas and Acinetobacter (NFB) (75- 22.12%), Acinetobacter spp. (53 - 15.63%), Pseudomonas aeruginosa and Proteus (51 - 15.04%), and Escherichia coli (49 - 14.45%). The most common isolates were from respiratory tract (394 isolates � 69.61%). High rates of MDR were found for Pseudomonas aeruginosa (64.70%), MRSA (62.65%) and Klebsiella spp. (53.33%), while almost all of the isolated NFB strains were MDR (97.33%). There was statistic difference between the drug resistance rate of Klebsiella and E. coli strains to ceftazidime and ceftriaxone (p[0.001), cefuroxime (p[0.01) and to cefepime (p[0.01). The study revealed an alarming pattern of antibiotic resistance in the majority of ICU isolates.


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