טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHreish Maysa
SubjectThe Human Gastro Intestinal Tract Microbiota and
Carbapenem-Resistant Enterobacteriaceae (CRE)
Carriage
DepartmentDepartment of Medicine
Supervisors Clinical Professor Zaher Azzam
Dr. Gidon Berger
Full Thesis textFull thesis text - English Version


Abstract

Carbapenem-Resistant Enterobacteriaceae (CRE) is highly drug-resistant pathogens whose incidence is rapidly increasing in a variety of clinical settings. Infections caused by CRE have been associated with increased cost and length of stay as well as frequent treatment failures and death. Risk factors for infection include advanced age, being severely ill, previous treatment with antibiotics, organ or stem-cell transplantation, mechanical ventilation, and long hospital stays.

Carriage of CRE in the gastrointestinal tract (GIT) is important for several reasons. First, it may precede and possibly serve as a source for subsequent clinical infection in approximately 9% of carriers. Second, carriers may serve as an important reservoir for dissemination of CRE in healthcare facilities.

The intestinal microbiota can protect efficiently against colonization of many enteric pathogens, therefore, we hypothesize that imbalance of the GIT-associated microbial communities is associated with the incidence and prevalence of CRE colonization and subsequent infection.

Understanding the biology of this pathogen and its interactions with members of this ecological niche during the colonization may provide new modalities to limit pathogenesis.

Herein, we aimed to determine the structure of the GIT microbiota in patients colonized with CRE and to study the associations of CRE with specific microorganisms.

Method. In order to characterize the structure of the microbiota we utilized high throughput sequencing (HTS) to screen bacterial 16S rRNA genes. Fecal samples were collected from three groups; healthy adults (N=15), non-carriers hospitalized patients (N=19) and hospitalized patients - CRE carriers (N=29). The first two groups were used as control groups.

There was a strong effect of CRE carriage on the diversity and composition of the microbiota. Patients colonized by CRE have dysbiotic microbiota, especially in terms of community membership. As compared to non-carriers, CRE carriers have simplified microbial communities, showing lower phylogenetic diversity. The CRE patients are enriched with bacteria belongs to the Enterobacteriaceae family, especially enterobacter, erwinia, pantoea, klebsiella genuses. Concurrently with the bloom in Enterobacteriaceae family, a depletion of anaerobic commensals (F_Rikenellaceae, g_ Barnesiella, g_ Ornithobacterium (P_ Bacteroides), g_Faecalibacterium, Ruminococcus spp., g_ Coprococcus (P_firmicutes)) was observed. Conceivably, this "unhealthy microbiota" plays a central role in the high prevalence of infections and bacteremia observed in CRE carriers' patients.              

We examined several potential vectors that may induce change in microbiota. Their comparison between the groups did not show any significant difference in either.

Patients colonized by CRE have dysbiotic microbiota especially in terms of community membership and high rates of systemic infection.