Carbapenem-resistant Enterobacteriaceae Bloodstream Infections Research Articles

Clinical characteristics and risk factors for neonatal bloodstream infection due to carbapenem-resistant Enterobacteriaceae: A single-centre Chinese retrospective study

ObjectivesTo analyse the clinical characteristics and risk factors for bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) in neonates. MethodsThis single-centre, retrospective study included all patients with BSIs admitted to a neonatal intensive care unit between 1 January 2015 and 30 April 2022. The clinical and microbiological data of patients were collected; predictors of 30-day mortality in patients with CRE BSIs were also identified in this study. ResultsAmong the 224 neonates with Enterobacteriaceae BSIs, 39.29% (88/224) of the patients developed CRE BSIs. The 30-day mortality rate reached up to 21.59% (19/88). The Quick Sequential Organ Failure Assessment score > 2 (odds ratio [OR] and 95% credibility interval [CI]: 3.852 [1.111–13.356], P < 0.05), prior to more than two kinds of antibiotics use (OR and 95% CI: 9.433 [1.562–56.973], P < 0.05), pneumonia (OR and 95% CI: 3.847 [1.133–13.061], P < 0.05), and caesarean section (OR and 95% CI: 2.678 [1.225–5.857], P < 0.05) were independent risk factors associated with CRE BSIs. Moreover, the risk factors for mortality in neonates with CRE BSIs were significantly associated with neonatal Sequential Organ Failure Assessment score > 6 (OR and 95% CI: 16.335 [1.446–184.517], P < 0.05). ConclusionPrior to more than two kinds of antibiotics use, Quick Sequential Organ Failure Assessment score > 2, pneumonia and caesarean section were independent risk factors for CRE BSIs. The Neonatal Sequential Organ Failure Assessment score > 6 was a risk factor for mortality associated with CRE BSIs.

An Emerging Issue: Carbapenem-Resistant Enterobacteriaceae in Solid-Organ Transplantation.

Bloodstream infections caused by carbapenem-resistant bacteria have increased globally. Solid-organ transplant recipients are more prone to these infections. This study aimed to compare the clinical courses of carbapenem-susceptible and carbapenem-resistant Enterobacteriaceae bloodstream infections and to identify risk factors for carbapenem resistance in solid-organ transplant recipients. For this retrospective descriptive study, data for solid-organ transplant recipients (age ≥18) treated from 2015 to 2022 were obtained from medical records. Enterobacteriaceaepositive blood culture was screened from laboratory data. Among 72 patients, there were 100 bacteremia episodes. Patients included 40 kidney (55.6%), 21 liver (29.2%), 7 heart (9.7%), and 4 combined liver and kidney (5.6%) transplant recipients. Fifty-seven bacteremia episodes were recorded between 2015 and 2020, and 43 bacteremia episodes were recorded between 2020 and 2022. Carbapenem resistance was reported in 15.8% of patients before 2020, whereas this rate increased to 39.5% after 2020 (P = .007). Pitt bacteremia score ≥4 (P < .001), Charlson comorbidity index ≥4 (P = .021), chronic liver disease (P = .015), septic shock at admission (P = .001), hypotension at admission (P = .006), bacteremia episodes 48 hours after hospitalization (P = .004), hospitalization in the past 3 months (P = .004), and prior invasive procedure (P = .043) were significant factors for carbapenem resistance. Logistic regression analysis showed that bacteremia 48 hours after hospitalization (P = .002) and hospitalization in the past 3 months (P = .006) were independent risk factors. Carbapenem resistance increased significantly over the years. Bacteremia 48 hours after hospitalization and hospitalization within the past 3 months were determined to be risk factors for carbapenem resistance. Carbapenem-resistant infections are still nosocomial infections. Patients should be hospitalized for as a short time as possible, and both patients and their physicians should follow infection control and prevention methods.

Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: A retrospective cohort study

The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Management of Carbapenem-Resistant Enterobacteriaceae Bloodstream Infections: An Experience from a Tertiary Care Centre in Oman

The emergence of Carbapenem-resistant Enterobacteriaceae (CRE)is a public health concern worldwide. It is associated with increased mortality due to limited antibiotics available to treat CRE infections. The aim of this study was to understand the epidemiology of CRE infections, associated mortality, and available treatment options. All patients with CRE isolated in blood culture were identified between December 2011 and October 2019. Risk factors and mortality associated with each risk factor at 14 and 30 days were determined.55 cases of CRE bloodstream infections were isolated, with a median age of 56 years. Eighty-four percent of patients received treatment in the ICU. All cases were caused by Klebsiella pneumonia. The rate of resistance to the tested antibiotics was as follows: meropenem 92% (50/54), imipenem 75% (40/53), etrapenam 95% (19/20), Amikacin 71% (37/52), cotrimoxazole 73% (40/53), Gentamicin 47% (25/53) and colistin 7% (3/41). Major risk factors associated were the presence of a urinary catheter (84%), central venous catheter (78%), mechanical ventilation (74%) and post-surgery (67%). Mortality at 14 days and 30 days was 41%, and 52%, respectively. Univariate analysis showed that 14 days mortality was higher in patients with central venous catheter (P=0.01). Charlson's comorbidity index was associated with an increased risk of death at 30 days (P=0.04). There was no statistically increased survival in those treated with combination therapy at 30 days (P=0.5). The mortality of CRE infections seems to be high and optimal therapy is not yet well defined. Combination therapy is not associated with increased survival in this cohort of patients.

Carbapenem-Resistant Enterobacteriaceae Bacteraemia in Intensive Care Unit: A Descriptive Study on Risk Factors and Clinical Outcome

INTRODUCTION: Over the past 10 years, the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing dramatically with numerous hospital outbreaks reported. Bacteraemia caused by CRE have limited treatment options and have been associated with high mortality rates. As a result, preventing both CRE transmission and CRE bloodstream infections have become important objectives in managing intensive care unit (ICU) patients. The study aims to determine the incidence and risk factors of CRE bacteraemia in intensive care settings, and its’ clinical outcome. MATERIALS AND METHODS: A retrospective, descriptive study was conducted, where data of the patients admitted to general ICU of Hospital Pulau Pinang from January 2017 till December 2018 were collected and assessed for incidence, presence of predisposing factors and clinical outcome for CRE bloodstream infection. RESULTS: Out of 2,585 total ICU admissions, there were 37 cases of CRE bacteraemia with an incidence rate of 1.43%. An analysis of risk factors revealed that the use of indwelling catheter has the highest association with CRE bacteraemia in which 95% of the patients were exposed. The commonest organisms of CRE bacteraemia were Klebsiella pneumoniae (97.3%) and Escherichia coli (2.7%). The 30-day mortality rate after CRE bacteraemia was 78.4%. CONCLUSION: CRE bacteraemia among ICU patients showed a high mortality rate. Most of the patients were exposed to multiple risk factors. A high index of suspicion and rapid identification of patients at risk for CRE infection are important for effective therapy and initiation of infection control measures to prevent further spread.

Effects of rapid drug sensitivity testing for multidrug-resistant bacteria on the prognosis of patients with severe intra-abdominal infection

Objective: To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection. Methods: This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results: The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group (Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant (Z=-1.686, P=0.093). Conclusions: GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

Clinical Characteristics and Associated Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection.

Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae (CRE) significantly influences patient morbidity and mortality. We aimed to identify the characteristics, outcomes, and risk factors of mortality in adult patients with CRE bacteremia and elucidate the differences between carbapenemase-producing (CP)-CRE BSI and non-CP-CRE BSI. This retrospective study included 147 patients who developed CRE BSI between January 2016 and January 2019 at a large tertiary care hospital in South Korea. The patient demographic characteristics and clinical and microbiological data including the Enterobacteriaceae species and carbapenemase type were obtained and analyzed. Klebsiella pneumoniae was the most commonly detected pathogen (80.3%), followed by Escherichia coli (15.0%). In total, 128 (87.1%) isolates were found to express carbapenemase, and most CP-CRE isolates harbored blaKPC. The 14-day and 30-day mortality rates for CRE BSI were 34.0% and 42.2%, respectively. Higher body mass index (odds ratio (OR), 1.123; 95% confidence interval (CI), 1.012-1.246; p = 0.029), higher sequential organ failure assessment (SOFA) score (OR, 1.206; 95% CI, 1.073-1.356; p = 0.002), and previous antibiotic use (OR, 0.163; 95% CI, 0.028-0.933; p = 0.042) were independent risk factors for the 14-day mortality. A high SOFA score (OR, 1.208; 95% CI; 1.081-0.349; p = 0.001) was the only independent risk factor for 30-day mortality. Carbapenemase production and appropriate antibiotic treatment were not associated with high 14- or 30-day mortality rates. Mortality from CRE BSI was related to the severity of the infection rather than to carbapenemase production or antibiotic treatment, showing that efforts to prevent CRE acquisition rather than treatment following CRE BSI detection would be more effective at reducing mortality.

Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children's cancer hospital in Egypt (2013-2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4-8 μg/mL in 100 (45%) and >8 μg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 μg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups.

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study.

PurposeCarbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients.Patients and MethodsThis was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data.ResultsOf the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried β-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD.ConclusionIn summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

Demographic, clinical, and outcome characteristics of carbapenem-resistant Enterobacteriaceae over a 10-year period (2010–2020) in Oman

PurposeThe incidence of carbapenem-resistant Enterobacteriaceae (CRE) has increased in the last two decades, causing significant morbidity and mortality. Our study investigated the factors associated with mortality from CRE bloodstream infection in a single center in Oman. MethodsData from adult patients with CRE bacteremia, over a 10-year period, were retrospectively collected. Demographic and clinical characteristics were compared according to intensive care unit (ICU) admission status and mortality. A logistic regression model was used to evaluate factors associated with mortality. Results169 cases of CRE bacteremia were identified, of whom 93 (55%) required ICU admission and 96 (56.8%) died. Patients who required ICU care were more likely to require organ transplant (15% vs 4.0%; p = 0.02), be on immunosuppressants (31% vs 17%; p = 0.035), be transferred from other hospitals (40% vs 14%; p < 0.001), be colonized with CRE (73% vs 43%; p < 0.001), have vascular lines (85% vs 42%; p < 0.001), be on mechanical ventilation (91% vs 9.2%; p < 0.001), require a longer stay (37 vs 17 days; p < 0.001), and have increased mortality (80% vs 29%; p < 0.001). In the multivariate analysis, mechanical ventilation (adjusted odds ratio (aOR) 15.3; 95% confidence interval 5.39–43.2; p < 0.001) and prior use of the broad-spectrum antibiotics meropenem (p = 0.01) and piperacillin/tazobactam (p = 0.026) were associated with CRE mortality. ConclusionCRE bacteremia carries a high mortality rate in patients requiring ICU care. Implementation of infection control measures and antimicrobial stewardship programs are essential in reducing the rates of CRE 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.

Epidemiological, Clinical and Microbiological Characteristics of Patients with Bloodstream Infections Due to Carbapenem-Resistant K. Pneumoniae in Southern Italy: A Multicentre Study.

Background: In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality. Methods: All episodes of carbapenem-resistant E. coli (CREc) or K. pneumoniae (CRKp) BSI that were subject to a mandatory notification from January to December 2020 in all acute care hospitals and long-term care facilities of the Campania region in southern Italy were enrolled. All carbapenem-resistant strains were assessed through molecular tests for the presence of five carbapenemase gene families, i.e., K. pneumoniae Carbapenemase (KPC), oxacillinase-48 (OXA-48), New Delhi Metallo-β-lactamase (NDM), Verona integron encoded metallo-β-lactamase (VIM) and Imipenemase (IMP). Results: During the study period, a total of 154 consecutive non-repeated CRE BSI, all due to CRKp, were reported. The most frequently identified genes were KPC in 108 cases (70.1%), followed by metallo-betalactamases (MBL) (16.2%), and OXA-48 (2.6%); in 17 isolates (11%) no carbapenemase was detected. The overall mortality at 90 days was 41.9%. Using a log-rank test, patients without risk factors for CRE infections showed a significantly lower cumulative mortality (p = 0.001). After multivariate logistic regression analysis, the presence of at least one risk factor was the only predictor of mortality (OR: 1.7, 95% CI 1.2–6.1, p = 0.015). Conclusions. The study reported a non-negligible prevalence of MBL-producing organisms among CRKp isolated from blood cultures in our region. This data highlights the importance of molecular characterization of all clinical isolates of carbapenem-resistant organisms.

429. Infection Prevention During Use of a Warm Zone Model in Cohort Patient Care Locations during the COVID-19 Pandemic

BackgroundThe COVID-19 pandemic required hospitals to care for influxes of patients in cohort locations during critical shortages of personal protective equipment (PPE). Safety zones can be used to protect healthcare workers caring for patients with infectious pathogens. During the COVID-19 pandemic, our hospital developed a Warm Zone model (WZM) to streamline the care of patients with COVID. We established specific areas in our COVID cohort units where staff were permitted to bridge between rooms without doffing gowns, but still doffing gloves and performing hand hygiene between patients. We recognized that a WZM could inadvertently increase risk of nosocomial transmission of pathogens if gowns acted as fomites. For this reason, patients with known infectious pathogens were excluded from the WZM. To measure for unintended harmful consequences of the WZM, our Infection Prevention (IP) department performed surveillance for hospital onset (HO) Clostridioides difficile (CDI), Carbapenem-resistant enterobacteriaceae (CRE) and Methicillin-resistant Staphyloccocus aureus (MRSA) bloodstream infections on units that implemented the WZM.MethodsTwo intensive care units and 3 wards where COVID positive patients were cohorted were included in surveillance. The timeframe for this analysis was 7/1/2020 - 3/31/2021. An electronic surveillance system was used to measure HO infections. The National Healthcare Surveillance Network (NHSN) LabID definitions were used when determining HO CDI and MRSA bloodstream infections (BSI).ResultsDuring the study period, there were no HO CRE, 1 HO CDI, and 2 HO MRSA BSI in cohort units. There was no evidence to suggest that the HO CDI or HO MRSA BSI were associated with use of a WZM. During this time period, there were 14 cases of community onset (CO) CDI, 2 cases of CO MRSA BSI, and one CO CRE.ConclusionDuring use of a WZM in COVID cohort units, IP did not identify significant increase in HO CDI, CRE, or MRSA BSI compared to non-cohort units. We were limited in our ability to measure acquisition of pathogens because active surveillance screening for colonization was not performed. However, we were able to safely employ a WZM to streamline patient care in COVID cohort areas without evidence of causing nosocomial infections via patient-to-patient transmission.Disclosures All Authors: No reported disclosures

Socioeconomic Burden of Bloodstream Infections Caused by Carbapenem-Resistant Enterobacteriaceae.

BackgroundAlthough infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an urgent public health threat worldwide, the socioeconomic burden of CRE bloodstream infection (BSI) remains to be clarified.MethodsThis retrospective study included all patients infected with Escherichia coli or Klebsiella pneumoniae who were hospitalized for BSI from 2013 to 2015. Socioeconomic burden, including direct and indirect economic burden, was compared in patients infected with carbapenem-sensitive Enterobacteriaceae (CSE) and CRE following 1:1 propensity score matching (PSM) to control for confounding variables.ResultsData from 879 patients with Enterobacteriaceae BSI were evaluated, including 152 (17.3%) patients infected with CRE and 727 (82.7%) infected with CSE. PSM yielded 112 pairs of 224 patients. Median hospital length of stay did not differ significantly in the CRE and CSE groups (35 vs 29 days, P = 0.089), but in-hospital 28-day mortality rate was significantly higher in patients infected with CRE than with CSE (45.5% vs 32.1%, P = 0.040). Median direct economic burden was significantly greater in patients with CRE-BSI than with CSE-BSI during hospitalization ($24,940.1 vs 16,864.0, P = 0.017) but not during the period after infection ($10,403.4 vs 8498.0, P = 0.178). Drug expenditure accounted for the largest proportion of costs in both groups. The median disability-adjusted life year (DALY) was higher in CRE-BSI than in CSE-BSI patients, but the difference was not statistically significant (7.9 vs 6.7 years, P = 0.190). Median indirect economic burden did not differ significantly in these two groups ($3848.5 vs 1139.9, P = 0.304), although indirect economic burden increased significantly from 2013 to 2015 in patients with CRE-BSI.ConclusionCarbapenem resistance had a major impact on the clinical and socioeconomic burden of patients with Enterobacteriaceae BSI. The higher mortality rate in patients with CRE-BSI was associated with increased direct healthcare burden and indirect socioeconomic loss.

Economic Evaluations of New Antibiotics: The High Potential Value of Reducing Healthcare Transmission Through Decolonization.

Antibiotics designed to decolonize carriers of drug-resistant organisms could offer substantial population health benefits, particularly if they can help avert outbreaks by interrupting person-to-person transmission chains. However, cost effectiveness of an antibiotic is typically evaluated only according to its benefits to recipients, which can be difficult to demonstrate for carriers of an organism that may not pose an immediate health threat to the carrier. We developed a mathematical transmission model to quantify the effects of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among long-term acute care hospital inpatients: one assumed to decrease the death rate of patients with CRE bloodstream infections (BSIs) and the other assumed to decolonize CRE carriers after clinical detection. We quantified the effect of each antibiotic on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (direct and indirect effect) compared to usual care. We applied these results to a cost-effectiveness analysis with effectiveness outcome of life-years gained and assumed costs for antibiotic doses and for CRE BSI. The decolonizing antibiotic, once indirect effects were included, produced increased relative effectiveness and decreased relative costs compared to both usual care and the BSI treatment antibiotic. In fact, in most scenarios, the decolonizing drug was the dominant treatment strategy (ie, less costly and more effective). Antibiotics that decolonize carriers of drug-resistant organisms can be highly cost-effective when considering indirect benefits within populations vulnerable to outbreaks. Public health could benefit from finding ways to incentivize development of decolonizing antibiotics in the US, where drugs with unclear direct benefits to recipients would pose difficulties in achieving FDA approval and financial benefit to the developer.

Active screening of intestinal carbapenem-resistant Enterobacteriaceae in high-risk patients admitted to the hematology wards and its effect evaluation

目的观察血液科肠道碳青霉烯类耐药的肠杆菌科细菌（CRE）主动筛查患者CRE定植、感染的特征，并评价主动筛查结合加强干预在血液科患者CRE感染预防控制中的效果。方法以2017年3月至2019年12月血液内科接受化疗或免疫抑制治疗且预期会出现粒细胞缺乏（粒缺）的患者为研究对象，进行至少3个时间点（治疗前、治疗后粒缺期、粒缺伴发热期）的肠道CRE筛查，以2016年12月至2017年2月血液内科未开展肠道CRE主动筛查的、接受化疗或免疫抑制治疗的115例患者为历史对照组，两组患者均进行CRE感染实时监测，CRE筛查阳性者均采取接触隔离措施，CRE筛查阳性者出现发热或者感染症状时启动针对CRE联合抗生素治疗。结果主动筛查患者CRE定植率为16.46%（66/401）；病种分布上，以急性白血病定植率最高，为23.03%（26/113）。66例筛查阳性患者中，其中第1次筛查阳性患者为27例，占40.9%（27/66），第2次筛查阳性患者为15例，占22.7%（15/66），第3次及以后筛查阳性患者为24例，占36.4%（24/66）。CRE定植病原菌中耐碳青霉烯类肺炎克雷伯菌（CRKP）最多，占54.55%（36/66）。主动筛查患者CRE感染率（2.49%）及死亡率（50.00%）低于历史对照组的11.30%及69.23%；干预期间10例CRE血流感染患者病原菌种类与前期主动筛查病原菌完全相同，符合率为100.0%。结论血液科病房急性白血病患者CRE定植率最高，CRKP是CRE定植、感染的主要病原菌，提高筛查频率可以显著提高筛查阳性率，采取主动筛查并及早干预能有效降低血液科患者CRE发生率及死亡率，CRE筛查阳性病原菌与后续CRE感染病原菌符合率高。恶性血液病患者肠道CRE筛查可以对后期CRE血流感染起到预警以及优化抗菌药物使用的作用。

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BackgroundA consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI).MethodsWe retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary.ResultsDuring period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death.Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock.ConclusionThe increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

1826. Impact of Rapid Diagnostics and Ceftazidime–Avibactam on Mortality after Bacteremia Caused by Carbapenem-Resistant Enterobacteriaceae

BackgroundPatients with bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) have long delays until receipt of appropriate antimicrobial therapy and high mortality rates. Rapid molecular diagnostics and novel therapies, such as ceftazidime–avibactam (CAZ-AVI), offer promise to improve outcomes, but their clinical impact is unclear.MethodsWe conducted an observational study of patients with CRE BSI from January 2016 to June 2018 at 8 New York and New Jersey medical centers. Patient demographics, comorbidities, clinical presentations, diagnostic methods, and treatments were compared between patients who died within 30 days of BSI onset and survivors. Independent risk factors for mortality were identified using logistic regression. We then compared time to receipt of active antimicrobial therapy between patients whose positive blood culture bottles underwent testing for the Klebsiella pneumoniae carbapenemase gene (blaKPC PCR) and patients where this test was not used.ResultsWe identified 178 patients with CRE BSI (K. pneumoniae: n = 104, 58%; Enterobacter cloacae: n = 26, 15%; Escherichia coli: n = 26, 15%). The 30-day mortality rate was 38%. An increasing Acute Physiology and Chronic Health Evaluation II score (adjusted odds ratio [aOR] 1.06, P = 0.005) was independently associated with increased 30-day mortality; whereas, use of blaKPC PCR (aOR 0.31, P = 0.005), urinary tract source (aOR 0.12, P = 0.001), and source control (aOR 0.25, P = 0.001) were independently associated with survival. Initial targeted therapy with CAZ-AVI was associated with a 28% 30-day mortality rate, compared with a 49% 30-day mortality rate among patients who received a polymyxin or aminoglycoside (P = 0.036). Patients whose blood culture underwent blaKPC PCR were more likely to receive active antimicrobial therapy within 24 hours of BSI onset (42% vs. 28%; P = 0.07) and had a decreased median time until receipt of active therapy (25 hours vs. 46 hours; P = 0.07), although these differences did not achieve statistical significance.ConclusionThe use of PCR to rapidly identify blood cultures with blaKPC and definitive therapy with CAZ-AVI instead of polymyxins or aminoglycosides were associated with decreased mortality after CRE bacteremia.Disclosures All Authors: No reported Disclosures.

2439. The role of positive externalities in economic evaluations of new antibiotics: modeling the impact of reduced transmission in healthcare facilities

BackgroundPositive externalities - beneficial spillover effects enjoyed by individuals who are not the primary consumers of a good - are rarely considered in cost-effectiveness analyses (CEAs) of antimicrobial drugs that could reduce person-to-person transmission of the target pathogen. We developed a compartmental model to simulate the effect of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among hospital inpatients: one that treats bloodstream infections (BSIs) and one that decolonizes carriers. We assessed the contribution of positive externalities to the results of CEAs of these 2 antibiotics in the model.MethodsOur model tracked patients according to CRE carriage, clinical infection, and detection status. Rates of CRE acquisition depended on transmissibility of carriers in different states and were calibrated to data from long-term acute care hospitals. For the BSI treatment scenario we assumed the new drug would decrease the death rate and transmissibility of patients after CRE BSI onset. For the decolonization scenario we assumed the new drug would increase clearance of CRE carriage after clinical detection. For each scenario, we quantified the drug’s effect on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (total effect, i.e., direct plus indirect effect) compared with usual care. For the CEAs, the effectiveness outcome was life-years (LYs) gained and we assumed the new drug cost of $4,000 per dose and cost of a CRE BSI of $24,788.ResultsFor both the BSI treatment and decolonization scenarios, the total effect of introducing the new drug was greater than the direct effect alone, indicating the existence of positive externalities. Relative to usual care, the new drug led to a decrease in incremental cost and an increase in incremental effectiveness (see Figures 1 and 2).ConclusionThe inclusion of positive externalities in CEAs can have important effects on whether these new antibiotics are deemed cost-effective, due to their potential for interrupting chains of transmission. In our model, the inclusion of these effects reduced the incremental cost and increased the incremental effectiveness of these antibiotics. Disclosures All authors: No reported disclosures.

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study

Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15-61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3-6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04-2·94), and decreased probability of discharge alive (0·61, 0·45-0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. bioMérieux.