Impact of Specific Antibiotic Therapies on the Prevalence of Human Host Resistant Bacteria (SATURN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01311154
Recruitment Status : Unknown
Verified March 2011 by Tel-Aviv Sourasky Medical Center.
Recruitment status was:  Recruiting
First Posted : March 9, 2011
Last Update Posted : March 9, 2011
European Union
Information provided by:
Tel-Aviv Sourasky Medical Center

Brief Summary:
The proposed study is distinctive in studying known carriers of resistant Enterobacteriaceae. It examines both phenotypic and genotypic expansion in the AMR bacterial population as a function of antibiotic treatment, and examines the effect of antibiotics on the dissemination of resistance genes from species to species. It will examine CRE, important emerging pathogens, which are a significant threat to public health, but yet not well studied. The proposed study will use an interdisciplinary approach, combining PK/PD, phenotypic, and genetic data to understand the effect of antibiotics on the likelihood of spread of AMR. Most previous studies have focused on the effect of antibiotic agents on clinical detection, infection or acquisition of AMR among non-carriers67,68. Other studies have looked at the effects on colonisation-resistance mostly among healthy volunteers69. Very few studies have examined the effects of various antibiotic agents on carriers of ARB and those focused primarily on vancomycin resistant enterococci (VRE)70. No similar studies have been conducted with regard to ESBL or to CRE. Correlation with clinical factors and environmental contamination has not been determined in previously published studies. The proposed study also extends the analysis to the effect of antibiotic treatment on dissemination of resistance genes which may be of great importance as these events may lead to emergence of new AMR strains and species. The proposed study not only examines the effects of various antibiotic agents and classes, but also the effects of duration of treatment and PK/PD indices on amplification of ARB. The study will also examine the effect of antibiotics on the epidemicity and fitness of colonising strains

Condition or disease
Focus of Study: Carriers of Resistant Enterobacteriaceae.

Detailed Description:

We will conduct an observational longitudinal prospective study in 3 hospitals in units with high prevalence of resistant organisms. Consenting patients will be screened for carriage of AMR organisms at admission, and those found to be carriers of the target ARB will be included in the longitudinal study. To improve the yield of screening we may use risk stratification based on risk factors identified at each center. Patients included in the longitudinal study will be asked to provide serial stool samples every 2-3 days during hospitalisation (rectal swab will be allowed as replacement for stool specimen, after developing appropriate methodology to correlate between stool samples and rectal swabs).

These samples will be analysed using quantitative cultures for the number of resistant organisms, and samples will be subject to quantitative real time PCR to quantify resistant genes (CTX-M, TEM, SHV, KPC, VIM as required). In parallel, environmental contamination will be examined and quantified using similar methods. Data will be collected daily regarding antibiotic treatment, other medications, clinical parameters, bowel movements and presence of diarrhoea, and various PK/PD indices. The target antibiotic for this study include commonly use agents in the hospital setting including quinolones, cephalosporins, piperacillin/tazobactam, ertapenem, imipenem, doripenem, metronidazole, clindamycin and aminoglycosides. The duration, the sequential order of treatment and PK/PD indices will be examined. The effects of surgical antibiotic prophylaxis will be examined as an important end point. The effects of the target antibiotic agents/classes on selection, enrichment, and spread of the target AMR organisms. Analyses will be conducted to compare: 1. the effects of various antibiotics 2. the effect of duration of therapy 3. the durability of the effect (posttreatment). 4. The effects of PK/PD indices.

Secondary analysis will examine the risk of developing infections as function of various factors including time and load of carriage of resistant organisms and of exposure to antibiotics will be performed. Correlation with clinical isolates will be performed including typing, gene and plasmid analyses to determine correlation between colonising and infecting strains. Experiment simulating patient contact will be conducted to examine contamination of hands, gloves and gowns after contact in order to correlate between environmental contamination and contamination of healthcare workers. Additional work will be conducted on profiling bacterial communities by DNA fingerprinting techniques using length hetrogeneity (LH-PCR) and automated ribososmal internal spacer analysis (ARISA) on a sample of the patients studied.

Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Official Title: Impact of Specific Antibiotic Therapies on the Prevalence of Human Host Resistant Bacteria - WP5
Study Start Date : February 2011
Estimated Primary Completion Date : February 2013
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics
U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
known carriers of resistant Enterobacteriaceae

Inclusion Criteria:

known carriers of resistant Enterobacteriaceae

Exclusion Criteria:

no exclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01311154

Tasmc Recruiting
Tel-aviv, Israel, 64239
Contact: Meital Kazma, Msc    03-6973625      
Contact: Shimrit Chone, Msc    03-6973625      
Sponsors and Collaborators
Tel-Aviv Sourasky Medical Center
European Union

Additional Information:
Responsible Party: yehuda carmeli, Tel Aviv Sourasky Medical Center Identifier: NCT01311154     History of Changes
Other Study ID Numbers: TASMC-0425-10-TLV
First Posted: March 9, 2011    Key Record Dates
Last Update Posted: March 9, 2011
Last Verified: March 2011

Keywords provided by Tel-Aviv Sourasky Medical Center:
resistant Enterobacteriaceae

Additional relevant MeSH terms:
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents