Carbapenem-susceptible Enterobacteriaceae Research Articles

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.

Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections

Background Carbapenem-resistant Enterobacteriaceae (CRE) is currently an emerging global public health problem and has significant negative impacts in many countries. This study aimed to identify risk factors associated with the mortality and readmission of CRE- and carbapenem-susceptible Enterobacteriaceae (CSE)–infected patients in Thailand. Length of stay (LOS) and the cost of treatment for the infections were also investigated. Method A retrospective cohort study was conducted in patients with CRE- and CSE-positive cultures from January 2016 to June 2019 in an advanced-level government hospital in Thailand. Risk factors for mortality and readmission were analyzed by logistic regression analysis. The differences in LOS and cost of treatment between CRE- and CSE-infected patients were analyzed by the independent t test. Results A total of 316 and 329 of the patients that were CRE and CSE culture positive, respectively, were included. Carbapenem-resistant Enterobacteriaceae was significantly associated with 30-day mortality [adjusted odds ratio (aOR), 2.86; 95% confidence interval (CI), 1.84–4.44; P &lt; 0.001] and with 90-day mortality (aOR, 3.11; 95% CI, 2.01–4.83; P &lt; 0.001). Factors that increased the risk of 30-day mortality and 90-day mortality were the Charlson Comorbidity Index score, the number of days with an invasive device or indwelling line, septic shock, acute respiratory failure, site of severe infection, and moderate to severe renal impairment. Carbapenem-resistant Enterobacteriaceae was also associated with 90-day readmission rate (aOR, 3.24; 95% CI, 1.85–5.70; P &lt; 0.001). The LOS of CRE-infected patients and CSE-infected patients was significantly different and was 29.18 ± 36.44 and 9.78 ± 12.77 days, respectively (P &lt; 0.001). The cost of treatment in CRE- and CSE-infected patients was significantly different (P &lt; 0.001). The cost in CRE-infected patients was 181,183.65 ± 281,325.26 baht, whereas the cost in CSE-infected patients was 53,296.75 ± 79,316.67 baht (P &lt; 0.001). Antibiotics for CRE-specific therapy including colistin, fosfomycin, tigecycline, or aminoglycosides, that were prescribed in combination were the mainstay treatments. Conclusions Carbapenem-resistant Enterobacteriaceae was an independent predictor for mortality and readmission. Length of stay and cost of treatment in CRE-infected patients were significantly higher than in CSE-infected patients.

Impact of carbapenem resistance on mortality in patients infected with Enterobacteriaceae: a systematic review and meta-analysis

ObjectivesTo provide a comprehensive assessment of the impact of carbapenem resistance on mortality among patients infected with Enterobacteriaceae and to explore the source of heterogeneity across studies.DesignThis systematic review was...

Risk factors and clinical impact of bacteremia due to carbapenem-nonsusceptible Enterobacteriaceae: A multicenter study in southern Taiwan.

The emergence of carbapenem-non-susceptible Enterobacteriaceae (CnSE) infections is a public health threat. This study investigated the risk factors and clinical impact of bacteremia due to CnSE. The study was conducted at three hospitals in southern Taiwan between January 1, 2017, and October 31, 2019. Only the first episode of CnSE bacteremia from each adult was included. For one episode of CnSE bacteremia, two subsequent bacteremic episodes due to carbapenem-susceptible Enterobacteriaceae isolates in each hospital were included as the controls. Among a total of 641 episodes of monomicrobial Enterobacteriaceae bacteremia were noted, 47 (7.3%) of which were of CnSE bacteremia. Ninety-four episodes of carbapenem-susceptible Enterobacteriaceae (CSE) bacteremia were selected as the controls for further analyses. In the multivariate analysis, hypertension (odds ratio [OR], 4.21; P=0.005), Pitt bacteremia score (OR, 1.61; P=0.002), and nosocomial bacteremia (OR, 3.30; P=0.01) were associated with carbapenem nonsusceptibility among Enterobacteriaceae bacteremia. The most abundant CnSE isolate was Klebsiella pneumoniae (91.5%), followed by Klebsiella oxytoca (6.4%) and Escherichia coli (2.1%). Patients with CnSE bacteremia had a higher overall in-hospital mortality rate than those with CSE bacteremia (53.2% vs. 23.4%, P=0.001). Moreover, in the multivariate analysis, the in-hospital mortality was significantly associated with higher Pitt bacteremia score (OR, 1.38; P=0.02) and marginally associated with CnSE infections (OR, 2.44; P=0.06). Among adults with Enterobacteriaceae bacteremia, carbapenem nonsusceptibility, male sex, and the presence of hypertension or chronic kidney disease indicate a poor prognosis during hospitalization.

A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan.

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.

Incidence and risk factors of carbapenem-resistant Enterobacteriaceae infection in intensive care units: a matched case–control study

ABSTRACT Background Carbapenem-resistant Enterobacteriaceae (CRE) infection is associated with intensive care admissions, morbidity, and mortality. Our study aimed to determine the incidence, risk factors, and patient outcomes of CRE in the ICU units. Methods This was a retrospective matched case–control study of patients admitted to ICUs. Patients who have positive cultures of CRE and carbapenem-susceptible Enterobacteriaceae (CSE) were included in the study. Patients were randomly selected from a pool of CSE subjects in a ratio of 1:1 of CRE to CSE as control patients. Results The infection rate with CRE among all patients admitted to ICUs was 7.6% and the incidence of CRE infection was 5.6 per 1,000 person-day. The risk factors independently associated with CRE infection were: Higher Sequential Organ Failure Assessment (SOFA) and Nutrition Risk in Critically ill (NUTRIC) scores, prolonged ICU length of stay (LOS), previous surgery, dialysis and mechanical ventilation during ICU stay, and previous use of aminoglycoside and carbapenems. Conclusion In this retrospective study, the incidence of CRE infection was relatively elevated in patients admitted to ICU. Patients with high SOFA and NUTRIC scores, prolonged ICU LOS, previous surgery, dialysis and mechanical ventilation, and prior aminoglycosides and carbapenems use, may have an increased risk of CRE infection.

Epidemiology of Carbapenem-resistant Enterobacteriaceae in Egyptian intensive care units using National Healthcare\u2013associated Infections Surveillance Data, 2011\u20132017

ObjectiveTo describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system.MethodsDesign: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011–2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13.ResultsThere were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09).ConclusionsThis analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU’s .

495. Risk Factors of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections Among Intensive Care Unit (ICU) Patients in a Tertiary Hospital in the Philippines

BackgroundThe threat of Carbapenem-Resistant Enterobacteriaceae (CRE) is increasing worldwide, and the epidemiology, risk factors, and outcomes of CRE in the Philippines is unknown.MethodsWe performed a retrospective case–control study of 128 CRE cases and Carbapenem-Susceptible Enterobacteriaceae (CSE) controls matched 1:1 based on site of infection and date of admission among all adult patients in the Intensive Care Unit (ICU) between January 2014 and May 2018 at The Medical City. Predictors of CRE infection among matched cases and controls were determined through multiple conditional logistic regression analysis. In-hospital mortality was analyzed using z-test of two proportions and length of stay among patients with CRE and CSE were compared.ResultsThe mean age in both groups was similar at 65.8 (range 23–92) and 64.3 (range 23–98) years, respectively. There were more males among cases than controls [(76/128, 59%) vs. 62/128 (48%)]. Those with CRE were more likely to have a co-morbid illness and an invasive device. Pneumonia was the most common site of CRE infection (40%) followed by the urinary tract (27%). Enterobacter cloacae (54.68%) was the most common organism, followed by Klebsiella pneumoniae (30.46%). On univariate analysis, the use of piperacillin–tazobactam, third or fourth-generation cephalosporins and carbapenems, mechanical ventilation, and acute kidney injury (AKI) increased the risk of developing CRE infections by an OR of 7.5 (CI 1.88–29.95, P = 0.004), 9.32 (CI 1.48–58.59, P = 0.017), and 10.76 (CI 1.69–68.53, P = 0.012), respectively. Those with CRE had a higher in-hospital mortality than the CSE group [(49/79, 38.3%) vs. (33/95, 25.8%); P = 0.032]. Length of hospital stay among CRE cases was also longer with a mean of 43.9 vs. 28 days compared with controls.ConclusionIn our cohort, older patients w/ comorbidities developed CRE with pneumonia being the most common site of infection. Prior use of broad-spectrum antimicrobials, mechanical ventilation and AKI appeared to increase the risk of CRE infection in the ICU. CRE infection also increased patient mortality and length of hospital stay. Interventions that target these risk factors should be undertaken to help prevent CRE infection. Disclosures All authors: No reported disclosures.

Epidemiology and risk factors for carbapenem-resistant Enterobacteriaceae colonisation and infections: case-controlled study from an academic medical center in a southern area of China.

While the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) and related infections pose serious threats to global public health, the epidemiology and associated risk factors remain poorly understood and vary by geography. In a case-controlled retrospective study, we examined the prevalence, patient background and risk factors for CRE colonisation and infections, and all patient-derived CRE from January 2015 to January 2017. Isolated carbapenem-susceptible Enterobacteriaceae (CSE) from 2875 enrolled patients were randomly selected during the study. CRE colonisation and infections detection rates were 47/2875 (1.6%). Respiratory tract specimens were most frequently seen in 20/47 (42.6%) cases. Klebsiella pneumoniae was the main isolate in 35/47 (74.5%) CRE. As for carbapenemase, KPC-2-producing bacteria was most frequently detected in 38/47 (80.9%) Enterobacteriaceae. No underlying conditions (P=0.004), pulmonary diseases (P=0.018) and no antibiotics used prior to culture within 30 days (P<0.001) were statistically significant between the CRE and CSE groups. Klebsiellapneumoniae was the main isolate of CRE. The blaKPC-2 was the predominant CRE gene. Underlying conditions especially pulmonary diseases and antibiotics used prior to culture within 30 days represented key risk factors for acquisition of CRE.

A Multi-Centered Case-Case-Control Study of Factors Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults.

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population. A case-case-control study of patients (0-22 years) at 3 tertiary-care Chicago-area medical centers, 2008-2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls had negative cultures. Case-control matching was 1:1:3 by age, infection site and hospital. Statistical and molecular analyses were performed. Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, 2 were unrelated, non-ST258 KP strains harboring blaKPC-2, one was a ST258 KP harboring blaKPC-3, and the last was an E. coli containing blaKPC-2. KPC-CRE and CSE-infected patients had more multidrug-resistant organisms infections, long-term care facility admissions and lengths of stay (LOS) > 7 days before culture. KPC-CRE and CSE patients had more gastrointestinal comorbidities (odds ratios [Ors], 28.0 and 6.4) and ≥ 3 comorbidities (Or 15.4 and 3.5) compared with controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs, 11.4 and 6.1). Compared with controls, CSE patients had more prior fluoroquinolone use (OR, 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs, 10.0 and 8.0). Race, gender, LOS and mortality differences were insignificant. Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

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.

1182. Risk Factors for the Acquisition of IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan: A Matched Case–control Study

BackgroundThe majority of CRE in Japan are IMP-type carbapenemase-producing CRE (IMP-CRE). However, research on risk factors for the acquisition of IMP-CRE has been limited, and questions exist regarding whether IMP-CRE have risk factors similar to other types of CRE such as KPC.MethodsWe conducted a matched case–control study involving patients from whom IMP-CRE had been isolated. The controls were selected among patients with carbapenem susceptible Enterobacteriaceae (CSE). Non-meropenem-susceptible per CLSI criteria and/or ceftazidime-resistant Enterobacteriaceae were screened, and metallo-β-lactamase–positive isolates were examined for blaIMP by PCR (January 2012 to December 2016).ResultsNinety-six patients with CRE were matched with 96 patients with CSE. They comprised Enterobacter sp. (n = 132 [CRE: 66, CSE: 66], 68.8%) and Klebsiella pneumoniae (n = 60 [CRE:30, CSE:30], 31.2%), and bacteria were most commonly isolated from sputum (n = 76 [39.6%]), followed by urine (n = 62 [32.3%]). Background factors such as age (median = 75 [IQR: 66–84]), sex (male = 56.8%), and the Charlson comorbidity index (median = 2 [IQR: 1–3.8]) were similar between CRE and CSE. In multivariate analysis, independent risk factors were identified: history of gastrointestinal (GI) endoscopy or surgery, history of ICU stay, and a previous exposure within 1 month to penicillins with β-lactamase inhibitors, cephalosporines, or carbapabnems.ConclusionHistories of GI endoscopy and ICU stay as well as broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Infection control measures combined with enhanced antimicrobial stewardship are key to preventing the spread of IMP-CRE. Multivariate analysis of risk factors for isolation of IMP-CRE , n (%)VariablesCRE(n = 96)CSE(n = 96)Adjusted odds ratio(95% CI)AdjustedP-valueHistoryGI endoscopy or surgery28 (29)12 (13)3.03 (1.24–7.43)0.015ICU stay32 (33)18 (19)2.25 (1.0–5.04)0.049Device useNasogastric tube43 (45)24 (25)1.27 (0.58–2.78)0.547Urinary catheter59 (61)38 (40)1.66 (0.83–3.33)0.155Tracheotomy18 (19)7 (7)2.17 (0.71–6.59)0.172PEG tube10 (10)3 (3)3.89 (0.74–20.57)0.11Antibiotic exposure ≤1 monthPenicillins with β-lactamase inhibitors52 (54)27 (28)4.54 (2.17–9.49)<0.001Cephalosporines40 (42)19 (20)3.38 (1.54–7.43)0.002Carbapenems25 (26)10 (10)3.08 (1.24–7.66)0.015Disclosures All authors: No reported disclosures.

2416. Risk Factors and Outcomes of Bacteremia Caused by Carbapenem-Resistant Enterobacteriaceae Compared With Carbapenem Susceptible Enterobacteriaceae

BackgroundDue to shrinking therapeutic options, infections due to Carbapenem-resistant enterobacteriaceae (CRE) are an urgent threat in healthcare systems across the world. While the CRE phenotype is determined by a number a different genes, the metallo β-lactamases such as the NDM, are particularly prevalent in the South Asian region. Data regarding infections with CRE caused by these strains is relatively limited. Our objective was to compare the risk factors and outcomes (mortality and length of hospitalization) of bacteremia secondary to CRE with bacteremia secondary to carbapenem susceptible enterobacteriaceae (CSE).MethodsWe conducted a cross-sectional study on patients admitted between 2013 and 2016, to a large tertiary care hospital in Karachi, Pakistan. Patients with CRE bacteremia were matched for the same year with patients with bacteremia due to CSE. Patients with polymicrobial blood cultures were excluded. Clinical data of these patients were obtained using a structured performa.ResultsA total of 131 patients were enrolled (65 CRE and 66 CSE). The mean age was similar in both groups (51.8 years and 57.1 years in CRE and CSE patients respectively). Compared with CSE, CRE bacteremia was more likely to occur in patients with Diabetes Mellitus or those with a tracheostomy (P = 0.002 and 0.014, respectively). The most common source of CRE bacteremia was central line associated (24.6% of all cases) as opposed to urinary tract infections in those with CSE bacteremia (62.1% of all cases). Fewer patients with CRE bacteremia received appropriate antibiotics (72.3% vs. 81.8%). Mortality was over three times higher in patients with CRE (41.5% vs. 12.1%, P = 0.001). The mortality remained higher when adjusted for the severity of illness using the PITT-bacteremia score. Increased mortality was also associated with central venous catheterization in both CRE and CSE bacteremia, while urinary catheterization and hemodialysis were associated with mortality in patients in CSE bacteremia only. While length of ICU stay was similar between the two groups, the median length of hospital stay was longer in patients with CRE (median of 8 days vs. 6 days, P = 0.021)ConclusionCRE bacteremia was more likely associated with central lines and led to significantly higher mortality and length of stay.Disclosures All authors: No reported disclosures.

Role of Double-Carbapenem Regimen in the Treatment of Infections due to Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae: A Single-Center, Observational Study.

Purpose (i) To compare infections caused by carbapenem-susceptible (CS) and carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE); (ii) to evaluate the clinical effectiveness of the double-carbapenem (DC) regimen in comparison with the best available treatment (BAT) in infections caused by CP-CRE; and (iii) to determine the exact minimal inhibitory concentrations (MICs) of meropenem/ertapenem (MEM/ETP) and the degree of in vitro ETP+MEM synergism in subjects receiving the DC. Methodology Over a 3-year period (2014-2017), patients with infections due to Enterobacteriaceae were included in a single-center, retrospective, observational study. According to the susceptibility to carbapenems, subjects were divided into CSE and CP-CRE groups. CP-CRE group was further divided into subjects receiving the DC regimen and those treated with other regimens (BAT group). Clinical characteristics and the presence of 5th-day response and 60-day outcome were evaluated for DC and BAT groups. The determination of MEM and ETP actual MICs and the MEM+ETP synergistic activity were performed on strains obtained from subjects receiving the DC regimen. Results A total of 128 patients were included in the study: 55/128 (43%) with infections due to CP-CRE and 73/128 (57%) with infections due to CSE. Among CP-CRE (n=55), 21 subjects (39%) were treated with the DC regimen whereas 34 (61%) received BAT. No differences in terms of severity of infection, presence/absence of concomitant bacteremia, type of infection, and resolution of infection were found; in contrast, DC group tended to have a higher rate of sepsis or septic shock at the onset of infection and a higher rate of 5th-day response. MICs 50/90 were 256/512 and 256/256 μg/mL for MEM and ETP, respectively. Overall, complete in vitro synergism was found in 6/20 strains (30%). Conclusion The DC regimen is a valid and effective therapeutic option in patients with infections due to KPC producing CRE, including those with bacteremic infection and more severe clinical conditions. The clinical effectiveness is maintained even in the presence of extremely high MEM MICs.

Epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) and comparison of the phenotypic versus genotypic screening tests for the detection of carbapenemases at a tertiary level, academic hospital in Johannesburg, South Africa

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant infections and pose a threat to the viability of available antibiotics. Understanding the epidemiology of these infections will assist in guiding appropriate treatment and infection prevention and control (IPC) practices in an institution. In addition, the phenotypic carbapenemase-producing Enterobacteriaceae (CPE) screening tests are widely used in South Africa. However, there is no published literature on their performance against PCR in that setting. Therefore, CRE epidemiology and performance of the Modified Hodge with Imipenem and Imipenem + EDTA combined disk tests (CDT) was evaluated at a tertiary academic hospital in Johannesburg.Method: A retrospective collection of data was performed. Data from January 2015 to December 2016 of all clinical isolates that were CRE OR carbapenem-susceptible Enterobacteriaceae with at least one positive CPE screening test were collected. Information collected included the ward areas from which samples were sent, specimen type that cultured CRE, CRE identification and carbapenem MIC results, phenotypic and genotypic CPE results.Results: Certain ward areas recurred as predominant areas with CRE infection in the two-year period. The prominent sample types that cultured CRE, the predominant Enterobacteriaceae species and carbapenemases identified corresponded with national surveillance data. The predominant carbapenemase type and level of carbapenem resistance conferred changed within one year. The Hodge test performed poorly for carbapenemase detection. The CDT detected metallo-β-lactamases adequately.Conclusion: In this study, the use of the MHT to screen for CPEs performed poorly. Continued surveillance will (i) lead to an understanding of the patient population (including infection type) affected, (ii) detect changes in the carbapenemase profiles, and (iii) inform infection prevention and control and appropriate clinical management.

Increased 30-Day Mortality Associated With Carbapenem-Resistant Enterobacteriaceae in Children.

In this multicenter study, we identified an increased risk of 30-day mortality among hospitalized children with carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical cultures compared with those with carbapenem-susceptible Enterobacteriaceae. We additionally report significant variation in antibiotic treatment for children with CRE infections with infrequent use of combination therapy.

Association Between Carbapenem Resistance and Mortality Among Adult, Hospitalized Patients With Serious Infections Due to Enterobacteriaceae: Results of a Systematic Literature Review and Meta-analysis.

This study quantified mortality associated with serious infections caused by carbapenem-resistant (CRE) and carbapenem-susceptible Enterobacteriaceae (CSE). A systematic literature review was conducted, evaluating outcomes in hospitalized patients with CRE infections from a blood, urinary, pulmonary, or intra-abdominal source. A meta-analysis (MA) calculating odds ratios (ORs) for mortality was performed. Twenty-two studies met the criteria for inclusion in the MA: 12 included mortality data for CRE vs CSE populations. Compared with CSE, CRE was associated with a significantly higher risk of overall mortality (OR, 3.39; 95% confidence interval [CI], 2.35–4.89), as was monotherapy (vs combination therapy) treatment of patients with CRE infections (OR, 2.19; 95% CI, 1.00–4.80). These results document the increased mortality associated with serious CRE infections compared with CSE infections among hospitalized adults. It will be important to reevaluate the mortality in CRE and CSE populations, especially among patients who receive early appropriate therapy, as new antibiotics become available.

Rapid detection of carbapenemase activity of Enterobacteriaceae isolated from positive blood cultures by MALDI-TOF MS

BackgroundMatrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been proved to be a useful tool for identification of pathogens directly isolated from blood cultures in clinical microbiology laboratories. β-Lactam antibiotics are commonly used for treatment of bloodstream infections caused by Enterobacteriaceae strains, and carbapenem is the superlative class of β-lactam antibiotics. Since the carbapenem resistance rate of Enterobacteriaceae strains raised year by year, efficient detection of carbapenemase activity and timely delivery of carbapenem susceptibility reports of Enterobacteriaceae strains isolated from blood cultures is important for clinicians.MethodsWe used 64 simulated blood cultures to establish the method of MALDI-TOF MS based ertapenem hydrolysis assay. The cutoff value of logRQ calculated from the peaks intensity of ertapenem and its hydrolysate was first set to identify the strains with carbapenemase activity. Then, we detected and calculated the logRQ values of 385 Enterobacteriaceae strains from positive clinical blood cultures to distinguish the carbapenemase producers and noncarbapenemase producers.ResultsThe mean logRQ value of 32 noncarbapenemase producers was − 0.85 ± 0.14 in simulated blood cultures, while the logRQ value of 32 carbapenemase producers was 0.87 ± 0.55. Thus, the cutoff value of logRQ was set at − 0.45 with sensitivity of 100% and specificity of 100%. In 385 clinical positive blood cultures, the logRQ values of all carbapenem-susceptible Enterobacteriaceae strains (81.3%, 313/385) were < − 0.45. Comparing with the detection of carbapenemase genes, carbapenem-resistant Enterobacteriaceae strains (18.7%, 72/385) were well distinguished by MALDI-TOF MS based ertapenem hydrolysis assay with a sensitivity of 92.5% and specificity of 100%.ConclusionsOur data show that MALDI-TOF MS based ertapenem hydrolysis assay is a rapid and accurate method to detect carbapenemase activity of Enterobacteriaceae strains from positive blood cultures, and can be routinely performed in clinical microbiology laboratories.

The epidemiology and risk factor of carbapenem-resistant enterobacteriaceae colonization and infections: Case control study in a single institute in Japan.

While the emergence and spread of carbapenem-resistant enterobacteriaceae (CRE) carriage and infections are serious threats to public health worldwide, its prevalence and epidemiology are still unknown. For the purpose of examining the prevalence, patients' background and risk factors for CRE carriage and infections, we conducted this case-control study. We retrospectively reviewed all patients isolating CRE at Aichi Medical University hospital from January 2010 until March 2017. The patients isolated with carbapenem-susceptible enterobacteriaceae (CSE) were randomly selected during the study period. A total of 26 patients, isolating 28 CRE infections were enrolled in this study. The detection rate of CRE carriage and infection was 0.22% (28/12,600). Compared to the CSE group, the CRE group had poorer PS and higher CCI scores. The CRE group tended to stay longer in hospital (121 v.s. 63 days, p=0.052) and admission fee was much more expensive than CSE group (220,710 v.s. 69,904 JPY, p<0.001). PS 2-4 (ECOG) and CCI≧3 (p=0.002), prior hospitalization within 90 days (p=0.006) and prior antibiotics use within 90 days (p=0.005) were risk factors for acquisition of CRE by univariate analysis. The combination of PS 2-4 and CCI≧3 was an independent risk factor for CRE carriage and infection by multivariate logistic regression analysis. The combination of PS 2-4 (ECOG) and CCI score≧3 was an independent risk factor of CRE carriage and infections. The CRE group tended to stay longer in hospital, and the medical expense was much more expensive than those in the CSE group.

Detection of plasmid-mediated colistin-resistant and carbapenem-resistant genes by multiplex PCR

A multiplex PCR was described to simultaneously detect mcr-1 and frequently occurring carbapenem-resistant genes including blaKPC, blaNDM, blaIMP, and blaOXA-48-like in a single reaction. The PCR product sizes of these 4 carbapenem-resistant genes were 232 bp, 438 bp, 621 bp, and 798 bp for blaIMP, blaOXA-48-like, blaNDM, and blaKPC, respectively, whereas mcr-1 revealed 1126 bp of PCR product. This protocol accurately detected those resistant genes in agreement with the reference strains, 127 local carbapenem-resistant Enterobacteriaceae, 8 mcr-1 carrying Enterobacteriaceae, and 62 carbapenem-susceptible Enterobacteriaceae. This method will be useful for laboratory application and surveillance of carbapenem and/or colistin-resistant bacteria.