Factors associated with mortality in Infections caused by Carbapenem-resistant Enterobacteriaceae

Introduction: There is little information about weigh of factors possibly associated with mortality, in infections caused by Carbapenem-resistant Enterobacteriaceae (CRE) in Latin America. Methodology: A case-controls study nested in a historical cohort was performed including all patients with CRE infections diagnosed between June 2013 and December 2018 at Hospital Universitario San Ignacio in Bogotá, Colombia. Univariate and multivariate analysis were performed to compare cases of mortality within the first month after the infection diagnosis with surviving patients. Results: A total of 131 patients were included. The overall 30-day mortality rate was 38.17%. In the multivariate analysis, a direct association was found between mortality and septic shock (OR 26.7 CI6.6-107.3 p < 0.01), post-chemotherapy febrile neutropenia (OR 3.3 CI1.06–10.8 p = 0.04) and Charlson Index ≥ 3 (OR 5.5 CI 1.5-20.06 p < 0.01). An inverse association was found with interventions to control the infectious focus (OR 0.3 CI0.1-0.7 p < 0.01). The MIC of different antibiotics and the use of combined antibiotic therapy (triple therapy vs. double therapy or monotherapy) were not associated with mortality. Conclusions: In patients with CRE infections, septic shock, a Charlson comorbidity index ≥ 3, and post-chemotherapy febrile neutropenia are independently related to an increase in mortality. The control of the infectious focus is a protective factor. A rapid identification of these patients, and the implementation of measures to control infectious focus and to detect CRE colonization in patients who are going to be taken to myelosuppressive chemotherapy could impact positively the prognosis of these patients.

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Detailed characterization of an IncFII plasmid carrying blaOXA-48 from Lebanon

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa181 ◽

2020 ◽

Vol 75 (9) ◽

pp. 2462-2465 ◽

Cited By ~ 1

Author(s):

Jennifer Moussa ◽

Balig Panossian ◽

Elie Nassour ◽

Tamara Salloum ◽

Edmond Abboud ◽

...

Keyword(s):

Rapid Identification ◽

Complete Sequence ◽

Conjugative Plasmid ◽

Incompatibility Group ◽

Carbapenem Resistant ◽

Class D ◽

Long Read ◽

Important Challenge ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background The spread of carbapenem-resistant Enterobacteriaceae is an important challenge and an increasing healthcare problem. OXA-48 is a class D carbapenemase that is usually localized on a conjugative plasmid belonging to the IncL incompatibility group. Methods In this study, we used a combination of short- and long-read WGS approaches and molecular typing techniques to characterize the genetic environment of the smallest reported 27 029 bp IncFII plasmid carrying blaOXA-48 (pLAU-OXA48). Results The plasmid recovered from a clinical Escherichia coli isolate was positive for blaOXA-48, which was located within the Tn6237 composite transposon. Primers targeting junctions between the IncF fragment and Tn6237 for the rapid identification of pLAU-OXA48-like plasmids were designed. Conclusions To our knowledge, this is the first report showing the complete sequence of an IncFII plasmid carrying blaOXA-48 within Tn6237 using hybrid assembly of long- and short-read sequencing.

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Appropriate Treatment for Bloodstream Infections Due to Carbapenem-Resistant Klebsiella pneumoniae and Escherichia coli: A Nationwide Multicenter Study in Taiwan

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy336 ◽

2018 ◽

Vol 6 (2) ◽

Cited By ~ 1

Author(s):

Yi-Tsung Lin ◽

Chin-Fang Su ◽

Chien Chuang ◽

Jung-Chung Lin ◽

Po-Liang Lu ◽

...

Keyword(s):

Escherichia Coli ◽

Multivariate Analysis ◽

Klebsiella Pneumoniae ◽

Multicenter Study ◽

Bloodstream Infections ◽

Carbapenem Resistant ◽

Appropriate Treatment ◽

Comorbidity Index ◽

Enterobacteriaceae Infections ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background In a multicenter study from Taiwan, we aimed to investigate the outcome of patients who received different antimicrobial therapy in carbapenem-resistant Enterobacteriaceae bloodstream infections and proposed a new definition for tigecycline use. Methods Patients from 16 hospitals in Taiwan who received appropriate therapy for bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae and Escherichia coli were enrolled in the study between January 2012 and June 2015. We used a cox proportional regression model for multivariate analysis to identify independent risk factors of 14-day mortality. Tigecycline was defined as appropriate when the isolates had a minimum inhibitory concentration (MIC) ≤0.5 mg/L, and we investigated whether tigecycline was associated with mortality among patients with monotherapy. Results Sixty-four cases with carbapenem-resistant K pneumoniae (n = 50) and E coli (n = 14) bloodstream infections were analyzed. Of the 64 isolates, 17 (26.6%) had genes that encoded carbapenemases. The 14-day mortality of these cases was 31.3%. In the multivariate analysis, Charlson Comorbidity Index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42; P = .022) and colistin monotherapy (HR, 5.57; 95% CI, 2.13–14.61; P < .001) were independently associated with 14-day mortality. Among the 55 patients with monotherapy, the 14-day mortality was 30.9% (n = 17). Tigecycline use was not associated with mortality in the multivariate analysis. Conclusions Tigecycline monotherapy was a choice if the strains exhibited MIC ≤0.5 mg/L, and colistin monotherapy was not suitable. Our findings can initiate additional clinical studies regarding the efficacy of tigecycline in carbapenem-resistant Enterobacteriaceae infections.

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2134. Differential Changes in Breath Volatile Metabolites to Identify Carbapenem-Resistant Enterobacteriaceae (CRE) in a Murine Pneumonia Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1814 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S722-S723

Author(s):

Nour Ismail ◽

Hazem Albashash ◽

Mahesh J Thalavitiya Acharige ◽

Mohamad Hejazi ◽

Carmen Leon Astudillo ◽

...

Keyword(s):

Bacterial Species ◽

Rapid Identification ◽

Metabolic Responses ◽

P Value ◽

Species Pair ◽

E Coli ◽

Volatile Metabolites ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background CRE infections cause significant mortality, in large part because rapid identification of these infections is challenging. We tested the hypothesis that CRE and their isogenic carbapenem-susceptible counterparts have differential metabolic responses to carbapenem therapy. Methods We generated isogenic pairs of E. coli, E. cloacae, and K. pneumoniae by inserting a blaNDM-1-containing plasmid into carbapenem-susceptible E. coli, E. cloacae, and K. pneumoniae. We confirmed phenotypic meropenem (MPM) resistance per CLSI breakpoints for Enterobacteriaceae (MIC ≥4) in the NDM-1+ member and susceptibility (MIC≤1) in the NDM-1- member of each pair. We administered 2 × 108 CFU of each isolate intranasally to 23–28 g male C57BL/6J mice, infecting 6 mice with the NDM-1+ member and 6 with the NDM-1− member of each species pair (12 mice per bacterial species). 24 hours after infection, we treated 3 mice in each NDM-1+ and NDM-1− bacterial species cohort with MPM over 4 hours, and the other 3 mice in each cohort with saline over 4 hours as controls, confirming adequate infection (a target of 106 CFU/g of lung tissue) in quantitative lung homogenate cultures. We then collected breath samples from each mouse via tracheostomy using a murine ventilator, identifying all volatile metabolites in each sample using thermal desorption-gas chromatography/tandem mass spectrometry. We used Wilcoxon tests to examine differences in metabolite abundance between MPM and saline-treated control mice in the NDM-1+ and NDM-1− a member of each species pair, with a two-sided P-value threshold of < 0.1. Results Several breath volatile metabolites changed differentially within each NDM-1+/NDM-1- pair, outlined in Table 1 (E. coli), Table 2 (E. cloacae), and Table 3 (K. pneumoniae). Each listed metabolite that changed with MPM did not change with MPM in mice infected with each isogenic counterpart Conclusion There are differential in vivo metabolic responses with effective vs. ineffective treatment of mice with pneumonia caused by E. coli, E. cloacae, and K. pneumoniae pairs that are genetically identical other than blaNDM-1; this differential treatment response can potentially be used to identify these infections. Disclosures All authors: No reported disclosures.

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2293. Revival of Polymyxins: A Single-Center Historical Cohort of Critically Ill Patients in Brazil

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1971 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S786-S786

Author(s):

Claudia Maria Dantas de Maio Carrilho ◽

Thalita Bento Talizin ◽

Camila R Lopes ◽

Isabella Patruceli Azevedo ◽

Kesia Paes ◽

...

Keyword(s):

Septic Shock ◽

Critically Ill Patients ◽

Polymyxin B ◽

University Hospital ◽

Rank Test ◽

Resistant Bacteria ◽

Historical Cohort ◽

Saps 3 ◽

Carbapenem Resistant ◽

Log Rank Test

Abstract Background The epidemiological scenario of multidrug-resistant bacteria has brought polymyxins back to medical prescriptions, as they are last-line therapy against carbapenem-resistant bacteria. There is a lack of knowledge of which is the best way to use this drug, especially in critically ill patients. We aimed to evaluate polymyxin use in an intensive care unit (ICU) in a university hospital and to describe its epidemiological characteristics. Methods This historical cohort included all consecutive patients who used polymyxins to treat ventilator-associated pneumonia from January 1, 2017 to January 31, 2018, during hospitalization in an ICU from a public university hospital, endemic for carbapenem-resistant bacteria, in Londrina, Brazil. Microbiological processing for diagnosis followed the guidelines from the Clinical and Laboratory Standards Institute (CLSI). Statistical analyses were performed using MedCalc for Windows, version 18.9 (MedCalc Software, Ostend, Belgium) and significance level adopted was 0.05. Results There were 179 patients; median of age was 57 years (IQR: 40.0 - 70.75). Polymyxin B was the most prescribed polymyxin (97.2%). Most of the patients had comorbidities (72.6%). Age was higher in the group of patients who died (60.0 vs. 36.5 years, P < 0.0001). Comorbidities prevalence was higher in non-survivors (80.7% vs. 38.2%, P < 0.0001). Sequential Organ Failure Assessment (SOFA) score on polymyxin prescribing day was higher in non-survivors (8.0 vs. 7.0, P = 0.0093), as well as Simplified Acute Physiology Score 3 (SAPS 3) score (70.7 vs. 59.35, P = 0.0003). Thirty-day mortality was 43%. Analysis of 14-day survival showed a higher mortality for patients who had sepsis (Log-rank test, P = 0.0284) and septic shock (Log-rank test, P = 0.0065). Acinetobacter baumannii was the most common etiologic agent, in 125 samples (73.9%), with 97.6% of resistance to carbapenem and 5.6% of resistance to polymyxins. Conclusion Polymyxin B was the most prescribed polymyxin. Age was higher in non-survivors, as well as comorbidities prevalence, SOFA and SAPS 3 scores. Patients with sepsis and septic shock showed a 14-day higher mortality. Acinetobacter baumannii was the most isolated agent. Carbapenem resistance was high. Disclosures All authors: No reported disclosures.

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Body size and physical exercise, and the risk of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517699289 ◽

2017 ◽

Vol 24 (3) ◽

pp. 270-278 ◽

Cited By ~ 15

Author(s):

Marianna Cortese ◽

Trond Riise ◽

Kjetil Bjørnevik ◽

Kjell-Morten Myhr ◽

Keyword(s):

Multiple Sclerosis ◽

Body Size ◽

Physical Exercise ◽

Aerobic Fitness ◽

Protective Factor ◽

Cox Regression ◽

Large Body ◽

Adjusted Relative Risk ◽

Inverse Association ◽

Historical Cohort

Background: Whether large body size increases multiple sclerosis (MS) risk in men is not well understood. Concurrently, physical exercise could be an independent protective factor. Objective: To prospectively investigate the association between body mass index (BMI) and aerobic fitness, indicators of body size and exercise, and MS risk in men. Methods: We performed a population-based nested case-control study within the historical cohort of all Norwegian men, born in 1950–1975, undergoing mandatory conscription at the age of 19 years. 1016 cases were identified through linkage to the Norwegian MS registry, while 19,230 controls were randomly selected from the cohort. We estimated the effect of BMI and fitness at conscription on MS risk using Cox regression. Results: Higher BMI (≥25 vs 18.5–<25 kg/m2) was significantly associated with increased MS risk (adjusted relative risk (RRadj) = 1.36, 95% confidence interval (CI): 1.05–1.76). We also found a significant inverse association between aerobic fitness (high vs low) and MS risk independent of BMI (RRadj = 0.69, 95% CI: 0.55–0.88, p-trend = 0.003), remaining similar when men with MS onset within 10 years from conscription were excluded ( p-trend = 0.03). Conclusion: These findings add weight to evidence linking being overweight to an increased MS risk in men. Furthermore, they suggest that exercise may be an additional modifiable protective factor for MS.

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