scholarly journals 518. Comparing the Mortality of Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S249-S250
Author(s):  
Hyeonji Seo ◽  
Eunmi Yang ◽  
Seongman Bae ◽  
Hyemin Chung ◽  
Eunbeen Cho ◽  
...  

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infection is an emerging clinical issue. One of the mechanisms of carbapenem-resistance is carbapenemase production. This study aimed to identify whether clinical outcomes differ by CRE resistance mechanism and to evaluate risk factors for mortality in patients with CRE bacteremia. Methods We conducted a retrospective cohort study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE and non-CP-CRE bacteremia during January 2011 to October 2018. Only monomicrobial Escherichia coli or Klebsiella pneumoniae bacteremia were included in the study. A modified carbapenem inactivation method was used for phenotypic detection of carbapenemase production. The presence of a variety of carbapenemase genes was evaluated by PCR with specific primers. Results Of 134 patients with monomicrobial CRE bacteremia, 48 (35.8%) were infected with CP-CRE, and 86 (64.1%) were infected with non-CP-CRE. The most common carbapenemase in CP-CRE isolates was KPC (66.7%), followed by NDM-1 (18.8%), OXA-48-like (10.4%), and VIM (4.1%). Baseline characteristics were similar between the two groups (Table 1). However, the CP-CRE group was significantly more likely to undergo removal of eradicable foci and to have meropenem MIC >8 µg/mL. A total of 33 (24.6%) patients died within 14 days, including 9 (18.8%) in the CP-CRE group and 24 (27.9%) in the non-CP-CRE group. Deceased patients were more likely to have a higher Pitt bacteremia score, nosocomial acquisition, ineradicable or not-eradicated foci, immunosuppressant use, inappropriate definitive treatment (Table 2). Combination therapy for definitive treatment was associated with decreased mortality. In a multivariate analysis including carbapenemase production, a higher Pitt bacteremia score (aOR, 5.15), ineradicable or not-eradicated foci (aOR, 4.05) and combination therapy for definitive treatment (aOR, 0.35) were independent risk factors for mortality. Conclusion Our study suggests that carbapenemase production is not a mortality risk factor in CRE bacteremia and provides additional evidence for early source control and combination therapy. Disclosures All authors: No reported disclosures.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S95-S96
Author(s):  
Eunbeen Cho ◽  
Hyo-Ju Son ◽  
Seongman Bae ◽  
Hyeonji Seo ◽  
Eunmi Yang ◽  
...  

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is an emerging clinical issue and shows high mortality rates. There are a few studies that have evaluated the microbiologic risk factors for mortality in CRAB bacteremia. Aim of this study is to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. Methods Adult patients with monomicrobial CRAB bacteremia at a 2,700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled in the study. Risk factors for 30-day mortality were evaluated through a detailed clinical and microbiological analysis of study patients. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and genotyping by multilocus sequence typing (MLST). Results A total of 164 patients were enrolled and 90 (55%) died within 30 days. Of the 164 patients, 111 (68%) were male and median age was 66.5 years. The most common MLST genotype was ST191 (80 isolates, 49%), followed by ST451 (14%) and ST784 (13%), and 12 (7%) isolates were resistant to colistin (MIC ≥4 mg/L). Deceased patients were more likely to have hematologic malignancy, neutropenia, pneumonia, and primary bacteremia; less likely to have solid tumor, catheter-related infection, and biliary tract infection; more likely to have a high Pitt bacteremia score; and less likely to receive appropriate antibiotic treatment, colistin, and combination therapy with colistin and tigecycline, compared with surviving patients (Table 1). Genotype, colistin MIC, and colistin resistance were not associated with mortality (Figure 1 and 2). In multivariable analysis, neutropenia (aOR, 3.25; 95% CI, 1.18–8.95), catheter-related infection (aOR, 0.33; 95% CI, 0.11–0.99), biliary tract infection (aOR, 0.20; 95% CI, 0.04–0.99), a high Pitt bacteremia score (aOR,1.42; 95% CI, 1.20–1.67), and combination therapy with colistin and tigecycline (aOR, 0.36; 95% CI, 0.14–0.92) were independent risk factors for mortality (Table 2). Conclusion Clinical factors such as the site of infection, severity of bacteremia, and specific combination therapy rather than microbiologic factors contributed to mortality in CRAB bacteremia. Appropriate combination therapy may help improving outcomes in CRAB bacteremia. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Hyo-Ju Son ◽  
Eun Been Cho ◽  
Moonsuk Bae ◽  
Seung Cheol Lee ◽  
Heungsup Sung ◽  
...  

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. Methods Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing. Results A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95–12.42; P = .001), septic shock (aOR, 4.72; 95% CI, 2.12–10.49; P < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05–6.16; P = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors. Conclusions Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.


2020 ◽  
Vol 221 (Supplement_2) ◽  
pp. S156-S163 ◽  
Author(s):  
Jiao Liu ◽  
Lidi Zhang ◽  
Jingye Pan ◽  
Man Huang ◽  
Yingchuan Li ◽  
...  

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor patient outcomes. Data on risk factors and molecular epidemiology of CRE in complicated intra-abdominal infections (cIAI) in China are limited. This study examined the risk factors of cIAI with CRE and the associated mortality based on carbapenem resistance mechanisms. Methods In this retrospective analysis, we identified 1024 cIAI patients hospitalized from January 1, 2013 to October 31, 2018 in 14 intensive care units in China. Thirty CRE isolates were genotyped to identify β-lactamase-encoding genes. Results Escherichia coli (34.5%) and Klebsiella pneumoniae (21.2%) were the leading pathogens. Patients with hospital-acquired cIAI had a lower rate of E coli (26.0% vs 49.1%; P < .001) and higher rate of carbapenem-resistant Gram-negative bacteria (31.7% vs 18.8%; P = .002) than those with community-acquired cIAI. Of the isolates, 16.0% and 23.4% of Enterobacteriaceae and K pneumoniae, respectively, were resistant to carbapenem. Most carbapenemase-producing (CP)-CRE isolates carried blaKPC (80.9%), followed by blaNMD (19.1%). The 28-day mortality was 31.1% and 9.0% in patients with CRE vs non-CRE (P < .001). In-hospital mortality was 4.7-fold higher for CP-CRE vs non-CP-CRE infection (P = .049). Carbapenem-containing combinations did not significantly influence in-hospital mortality of CP and non-CP-CRE. The risk factors for 28-day mortality in CRE-cIAI included septic shock, antibiotic exposure during the preceding 30 days, and comorbidities. Conclusions Klebsiella pneumoniae had the highest prevalence in CRE. Infection with CRE, especially CP-CRE, was associated with increased mortality in cIAI.


2016 ◽  
Vol 64 (3) ◽  
pp. 257-264 ◽  
Author(s):  
Pranita D Tamma ◽  
Katherine E Goodman ◽  
Anthony D Harris ◽  
Tsigereda Tekle ◽  
Ava Roberts ◽  
...  

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. Methods We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes. Results There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were blaKPC (92%), followed by blaNDM (5%) and blaOXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01–24.81). Conclusion Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.


Author(s):  
Pranita D Tamma ◽  
Stephan Beisken ◽  
Yehudit Bergman ◽  
Andreas E Posch ◽  
Edina Avdic ◽  
...  

Abstract Background Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance. Methods Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy. Results Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase. Conclusions Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S242-S243
Author(s):  
Thana Khawcharoenporn ◽  
Wipada Laichuthai

Abstract Background This study aims to determine rates of subsequent carbapenem-resistance Enterobacteriaceae (CRE)-associated infections and prolonged colonization among patients colonized by CRE and to identify risk factors of such conditions. Methods This study was conducted among a cohort of hospitalized adult patients colonized by CRE at any sites from June 1, 2015 to December 31, 2018. The patients had been prospectively identified by the Infection Control (IC) Division of a Thai tertiary-care hospital. According to the hospital’s IC protocol, patients with CRE colonization/infections were isolated and underwent CRE cultured at the colonized/infected sites every week until the cultures have turned negative for 2 consecutive times. Prolonged colonization was defined as having CRE colonization more than 30 days. Results Of the 125 patients identified, 25 were excluded due to death, being transferred, or discharged within 48 hours of CRE colonization detected. The final cohort included 100 patients, the median age was 74 years, 48% were male, the most common colonized site was rectum (37%) and 20 patients (20%) developed subsequent CRE-associated infections. The median time from colonization to infection was 13 days and the most common site of infection was bloodstream (45%). Independent factors associated with subsequent CRE-associated infections were the number of colonization sites [adjusted odds ratio (aOR) 7.98, P < 0.001)], central line insertion during admission (aOR 7.97, P = 0.009) and receipt of vancomycin during admission (aOR 24.77, P = 0.02). Prolonged colonization was observed in 13 of 77 evaluable patients (17%). There were trends toward significance that the length of hospital stay and duration of antibiotic prior to colonization were associated with prolonged colonization (P < 0.10). Conclusion The findings suggest high rates of subsequent CRE-associated infections and prolonged colonization among the study population. Patients with risk factors for subsequent infections should be closely monitored and empirically-treated with antibiotics active against CRE while those with risk factors for prolonged colonization should receive continued surveillance and isolation to prevent CRE transmission. Disclosures All authors: No reported disclosures.


2021 ◽  
Author(s):  
Fahad Aleidan ◽  
Sara Albilal ◽  
Maha Alammari ◽  
Khalid Al Sulaiman ◽  
Mohammed Alassiri ◽  
...  

Abstract BackgroundSystemic infections are one of several risk factors leading to the development of inflammation and venous thromboembolism (VTE) formation.Aim of the studyTo assess the risk factors associated with the development of VTE during the stay of critically ill patients in the intensive care unit (ICU).Materials and methodsThis is a matched case-control study of patients with VTE admitted to the ICU, at a single centre, from January 1 2018 to December 31 2019. We included all adult patients who stayed more than two days before the development of VTE. Conditional logistic regression was used to estimate the odds ratio (OR) for the risk factors for VTE.ResultsUnivariate and multivariate analyses uncovered three of six factors to have significant influence in the development of VTE in ICU patients: Carbapenem-resistant Enterobactereaceae (CRE) infections (OR 2.95, 95% confidence interval (CI) 1.21–7.33, p = .010), length of ICU stay (OR 1.02, 95% CI 1.01–1.04, p = .011) and the sequential organ failure assessment (SOFA) score (OR 1.10, 95% CI 1.01–1.20, p = .031); all were found to be independent risk factors in the development of VTE.ConclusionOur findings suggest that in patients admitted to the ICU, CRE infection is a strong trigger to the development of VTE, and draw the attention of the treating clinicians to prioritise these infections in the management protocols to control infection-driven VTE in ICU patients.


Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Suay-García ◽  
Pérez-Gracia

Carbapenem-resistant Enterobacteriaceae (CRE) have become a public health threat worldwide. There are three major mechanisms by which Enterobacteriaceae become resistant to carbapenems: enzyme production, efflux pumps and porin mutations. Of these, enzyme production is the main resistance mechanism. There are three main groups of enzymes responsible for most of the carbapenem resistance: KPC (Klebsiella pneumoniae carbapenemase) (Ambler class A), MBLs (Metallo-ß-Lactamases) (Ambler class B) and OXA-48-like (Ambler class D). KPC-producing Enterobacteriaceae are endemic in the United States, Colombia, Argentina, Greece and Italy. On the other hand, the MBL NDM-1 is the main carbapenemase-producing resistance in India, Pakistan and Sri Lanka, while OXA-48-like enzyme-producers are endemic in Turkey, Malta, the Middle-East and North Africa. All three groups of enzymes are plasmid-mediated, which implies an easier horizontal transfer and, thus, faster spread of carbapenem resistance worldwide. As a result, there is an urgent need to develop new therapeutic guidelines to treat CRE infections. Bearing in mind the different mechanisms by which Enterobacteriaceae can become resistant to carbapenems, there are different approaches to treat infections caused by these bacteria, which include the repurposing of already existing antibiotics, dual therapies with these antibiotics, and the development of new ß-lactamase inhibitors and antibiotics.


2019 ◽  
Vol 13 (05) ◽  
pp. 357-364 ◽  
Author(s):  
Jianling Liu ◽  
Haichen Wang ◽  
Ziyan Huang ◽  
Xiaoyan Tao ◽  
Jun Li ◽  
...  

Introduction: Carbapenem-resistant Klebsiella pneumoniae (KP) serves as a major threat to onco-hematological patients, resulting in great morbidity and mortality. The purpose of our study was to identify the risk factors for KP bloodstream infections (BSIs) and mortality in onco-hematological patients. Methodology: A retrospective observation study was conducted on KP BSIs in the onco-hematology departments at Xiangya hospital from January 2014 to September 2018. Multivariate analysis was employed to identify the independent risk factors for carbapenem-resistant (CR) KP BSIs and related mortality. Results: A total of 89 strains of KP were analyzed in our study, in which 20 strains were CRKP. The only risk factor for CRKP BSI was carbapenem exposure within 30 days before the onset of BSIs (HR 25.122). The 30-day mortality was 24.7%. CRKP caused more mortality than carbapenem-susceptible KP (55.0% vs 15.9%, P = 0.001). In the multivariate analysis, unresolved neutropenia (HR 16.900), diarrhea (HR 3.647) and RDW > 14% (HR 6.292) were independent risk factors for mortality, and appropriate empirical therapy (HR 0.164) was protective against mortality. Conclusions: Our findings showed that carbapenem resistance was spreading in our setting, and a precise combination of antibiotics covering the common pathogen is crucial to improving patient survival.


Author(s):  
Nisha Patidar ◽  
Nitya Vyas ◽  
Shanoo Sharma ◽  
Babita Sharma

Abstract Objective Carbapenems are last resort antibiotics for multidrug-resistant Enterobacteriaceae. However, resistance to carbapenem is increasing at an alarming rate worldwide leading to major therapeutic failures and increased mortality rate. Early and effective detection of carbapenemase producing carbapenem-resistant Enterobacteriaceae (CRE) is therefore key to control dissemination of carbapenem resistance in nosocomial as well as community-acquired infection. The aim of present study was to evaluate efficacy of Modified strip Carba NP (CNP) test against Modified Hodge test (MHT) for early detection of carbapenemase producing Enterobacteriaceae (CPE). Material and Methods Enterobacteriaceae isolated from various clinical samples were screened for carbapenem resistance. A total of 107 CRE were subjected to MHT and Modified strip CNP test for the detection of CPE. Statistical Analysis It was done on Statistical Package for the Social Sciences (SPSS) software, IBM India; version V26. Nonparametric test chi-square and Z-test were used to analyze the results within a 95% level of confidence. Results Out of 107 CRE, 94 (88%) were phenotypically confirmed as carbapenemase producer by Modified strip CNP test and 46 (43%) were confirmed by Modified Hodge Test (MHT). Thirty-eight (36%) isolates showed carbapenemase production by both MHT and CNP test, 56 isolates (52%) were CNP test positive but MHT negative, eight (7%) isolates were MHT positive but CNP test negative and five (5%) isolates were both MHT and CNP test negative. There is statistically significant difference in efficiency of Modified CNP test and MHT (p < 0.05). Conclusion Modified strip CNP test is simple and inexpensive test which is easy to perform and interpret and gives rapid results in less than 5 minutes. It has high degree of sensitivity and specificity. Modified strip CNP test shows significantly higher detection capacity for carbapenemase producers as compared with MHT.


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