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

2018 ◽  
Vol 5 (10) ◽  
Author(s):  
Kathleen Chiotos ◽  
Pranita D Tamma ◽  
Kelly B Flett ◽  
Manjiree V Karandikar ◽  
Koorosh Nemati ◽  
...  

Abstract 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.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S330-S330
Author(s):  
Gabby LeBlanc ◽  
Brandon Brooks ◽  
Madeline Hartman ◽  
Maxwell B Hecht ◽  
Hoa Luong ◽  
...  

Abstract Background Infections with Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE) can result in a 50% mortality rate in compromised hosts. A major risk factor for clinical infection is intestinal colonization with CRE or VRE. There are currently no FDA-approved compounds to decolonize these organisms from the gastrointestinal tract (gut). Commensal microbes offer protection from pathogen infection; however, in immunocompromised hosts or with antibiotic treatment, the protective properties of the microbial community are compromised, leaving the gut susceptible to pathogen colonization. Higher concentrations of pathogens within the gut correlate with an increased risk of infection with MDROs. Our hypothesis is that reducing colonization of the gut with MDROs would reduce the likelihood of a clinical infection. Methods Kaleido built a platform that emulates the gut environment and allows for high throughput screening of Kaleido’s Microbiome Metabolic Therapies (MMT™) in human gut microbiomes ex vivo. Over 500 compounds were screened for their ability to reduce the levels of CRE and VRE in fecal microbial communities from both healthy subjects and critically ill patients receiving broad-spectrum antibiotics. Results Kaleido’s lead MMTs selectively favor the growth of the commensal microbiota at the expense of pathogens, resulting in a decrease of CRE and VRE from 80% of the initial community to 5% in a single batch culture, as measured by 16S rRNA gene and shotgun metagenomic sequencing. Lead MMTs do not support growth of CRE and VRE strains in culture, nor of other pathogens frequently encountered in critically ill and immunocompromised patients, such as Clostridium difficile and common fungal pathogens. Conclusion These results suggest that intervention with MMTs may reduce CRE and VRE colonization and support further evaluation in patients colonized with CRE or VRE pathogens. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S303-S303 ◽  
Author(s):  
Renee Ackley ◽  
Danya Roshdy ◽  
Jacqueline Isip ◽  
Sarah B, Minor ◽  
Amanda L Elchynski ◽  
...  

Abstract Background Options for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections were historically limited to antibiotics with limited efficacy and significant toxicities. Ceftazidime/avibactam (CA) and meropenem/vaborbactam (MV) are superior to older regimens; however, a direct comparison of the agents is lacking. This study compared clinical outcomes including recurrence of infection and emergence of drug resistance in patients who received CA vs. MV for CRE infections. Methods This was a multicenter, retrospective cohort study of adults with CRE infections who received CA or MV for ≥72 hours from February 2015 to October 2018. Patients with localized urinary tract infection were excluded. The primary endpoint was clinical success (30-day survival, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days in patients with bacteremia, absence of recurrent infection). Secondary endpoints included 30- and 90-day mortality, adverse events (AE), recurrent CRE infection within 90 days, and development of resistance in patients with recurrent infection. We conducted a post hoc subgroup analysis in patients with recurrence to compare development of resistance in those who received CA monotherapy, CA combination therapy, and MV monotherapy. Results 131 patients were included (CA: 105 patients, MV: 26 patients), 40% had bacteremia. No statistical difference in clinical success was observed between groups (62% vs. 69%, respectively, P = 0.49). Patients in the CA arm received combination therapy more often than patients in the MV arm (61% vs. 15%, P < 0.01). No difference in 30- and 90-day mortality resulted among groups, but numerically higher rates of AE were observed in the CA group (38% vs. 23%, P = 0.17). In patients with recurrent infection, development of resistance occurred more often with CA monotherapy, though not statistically significant (Table 1). One case of MV resistance was observed in a patient who had received 4 prior courses of MV, but this episode was outside of the study period. Conclusion Clinical success was similar between the groups despite MV being used more often as monotherapy. Development of resistance and rates of AE were higher in the CA group compared with MV therapy. Disclosures All authors: No reported disclosures.


2019 ◽  
Author(s):  
Ryuichiro Abe ◽  
Hideharu Hagiya ◽  
Yukihiro Akeda ◽  
Norihisa Yamamoto ◽  
Yoshikazu Ishii ◽  
...  

Abstract Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.


2018 ◽  
Vol 6 (2) ◽  
Author(s):  
Yi-Tsung Lin ◽  
Chin-Fang Su ◽  
Chien Chuang ◽  
Jung-Chung Lin ◽  
Po-Liang Lu ◽  
...  

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 &lt; .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.


2019 ◽  
Author(s):  
Ryuichiro Abe ◽  
Hideharu Hagiya ◽  
Yukihiro Akeda ◽  
Norihisa Yamamoto ◽  
Yoshikazu Ishii ◽  
...  

Abstract Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against IMP-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.


2020 ◽  
Vol 26 (6) ◽  
pp. 1156-1163 ◽  
Author(s):  
Matias Chiarastelli Salomão ◽  
Maristela Pinheiro Freire ◽  
Icaro Boszczowski ◽  
Sueli F. Raymundo ◽  
Ana Rubia Guedes ◽  
...  

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