Antibiotic Resistant Strain Clinical Trial
Official title:
Evaluation of the Emergence of the Resistance to Linezolid in Staphylococcus Epidermidis and Risk Factors Analysis : a Mono-centric Case-control Study
Understanding the emergence of linezolid-resistance in Staphylococci has been allowed in the
past years through the discovery of the clonal dissemination of a chromosomal cassette
carrying a modified crf gene. New mutations have even been described. Though, clinical
evidences are still lacking, especially concerning the factors associated to this emergence.
It could seriously become quite problematic to eliminate one of the last therapeutic weapon
at our disposal for the treatment of severe or complicated infections caused by resistant
strains of Staphylococci and Enterococci.
We aim to describe the mechanisms that permitted to this resistance to become clinically
significant, concerning meticillin-resistant Staphyloccocus epidermidis strains causing blood
stream infections in ICU patients, and show the clinical risk factors associated with it
through a case-control study on patients hospitalized in two ICUs of our hospital between
2011 and 2016.
Resistance to linezolid has been increasing in the past years, suggesting growing therapeutic
difficulties while narrowing the options for treating severe or complicated infections
involving Staphyloccoci or Enterococci strains. This emergence has been partially explained
after the discovery of chromosomal dissemination of a particular gene, named "crf",
conferring high level resistance to oxazolidinones.
Moreover, this mechanism has been showed as being prevalent in several countries across North
America, Asia, and Europe.
But still the link with clinical evidences has not yet been very well established.
In particular the role of S. epidermidis has become clinically significant concerning blood
stream infections and catheter-linked infections. The reality of the pathogenicity is more
widely accepted, especially regarding prosthetic joint infections, and immunocompromised
patient, as in hematology and oncology.
Thus, it appears necessary to provide more solid informations concerning the risk of using
this antibiotic in a high burden setting of resistance, where it might be prescribed
intensively on critical situations, and thus responsible for a high selection pressure of
resistance.
We aim to describe the emergence of the resistance to linezolid in meticillin-resistant S.
epidermidis strains in the two 20-beds ICUs of our Teaching Hospital, in the 5 past years,
between april 2011 and october 2016.
We conduct a case-control study between two populations of patients hospitalized in one of
these ICU.
They all presented a blood stream infection caused by a strain of S. epidermidis that was
resistant to meticillin, and diagnosed prospectively or retrospectively being resistant as
well to linezolid, or not. Indeed, microbiological data was quite easily available as all the
strains isolated from blood samples are conserved after congelation for many years.
Nevertheless, we lack the profile toward linezolid susceptibility as this antibiotic was not
routinely tested before 2014, corresponding to the moment we became aware of the problematic
rising. A previous work thus consists to establish the incidence of the resistance.
Comparison of these two populations through a case-control design study, accepting 2
control-patients for one case (matched on the period of hospitalization, mortality and
severity score at admission), might allow understanding risk factors of being infected with a
linezolid-resistant and meticillin-resistant S.epidermidis.
So to go further, we first conduct a phenotypic analysis in order to establish the incidence
of this resistance, in accordance with the 2016 EUCAST criteria. Association with genotypic
analysis using Pulsed-field gel electrophoresis and Multilocus-sequence typing will allow
underlining the impact of the presence of the crf gene, and mutations described as being
involved in high level resistance (mutations in domaine V of 23S ARN or ribosomal proteins L3
and L4).
All adult patient admitted to one of these two units can be included and evaluated if he
presented at least two blood cultures sampled at less than 48hours of interval, being
positive for the same strain (in accordance with the 2007 CTINILS definition). We considered
the catheter-linked infections as being apart if it was associated with positive blood
cultures.
We also search for clinical criteria supposed to be linked to an infection with such a
resistant strain; we check for the demographic data, conditions at admission, antibiotic
treatment before or at admission, procedures considered at high risk for health-care
infections such as surgery, especially in the period of great instability, also endovascular
procedures, like catheter implantation or extra-corporal assistance (Extra-corporal membrane
for oxygenation, Renal Replacement Therapy).
We examine the therapeutic options once the diagnosis of blood stream infections has been
made, the choice of antibiotic as treatment, and the outcome defined as cure or survival at
28 days, which is the period of matching patients.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06262009 -
Dynamics of AMR Spread, Persistence and Evolution Between Humans, Animals and Their Environment
|
||
Completed |
NCT04212403 -
Antibiotic Prophylaxis in Transurethral Prostate Resection (TURP) and Transurethral Bladder Tumour Resection (TURB)
|
N/A | |
Recruiting |
NCT04460313 -
Nasopharyngeal Carriage of S. Pneumoniae
|
N/A | |
Active, not recruiting |
NCT03208725 -
Childhood Acute Illness and Nutrition Network
|
||
Completed |
NCT03963297 -
Multicenter Evaluation of the Susceptibility of Enterobacteriaceae and Pseudomonas Aeruginosa to Ceftolozane/Tazobactam Combination
|
||
Active, not recruiting |
NCT05027893 -
Complications After Lower Third Molar Surgery
|
N/A | |
Completed |
NCT05551988 -
Predictors of Foot Amputation in Diabetic Foot Ulcers
|
||
Not yet recruiting |
NCT04795518 -
The Pattern of Antibiotic Prescription for Children Among a Group of Pediatric Dentists.
|
||
Recruiting |
NCT03767283 -
Carbapenem and Quinolone Resistance in Klebsiella Pneumoniae
|
||
Completed |
NCT03061097 -
Autologous Fecal Microbiota Transplantation to Prevent Antibiotic Resistant Bacteria Colonization
|
Phase 1 | |
Withdrawn |
NCT03391674 -
Fecal Microbiota Transplantation for Eradication of Carbapenem-resistant Enterobacteriaceae Colonization
|
N/A | |
Recruiting |
NCT04107194 -
Non-invasive Test-guided Tailored Therapy Versus Empiric Treatment for Helicobacter Pylori Infection.
|
Phase 3 | |
Completed |
NCT03884348 -
Tailored H. Pylori Eradication Based on Clarithromycin Resistance
|
||
Completed |
NCT04926935 -
Bloodstram Infections in ICU. Single Centre Observational Study.
|
||
Not yet recruiting |
NCT04269174 -
The Utility of Biofire Filmarray in Evaluation of Entero Pathogens Triggers in Patients With Chronic Diarrhea
|
||
Completed |
NCT03167398 -
Fecal Microbiota Transplantation for Eradication of CRE
|
Phase 1/Phase 2 | |
Completed |
NCT03866291 -
ESBL in Patients Returning to Sweden With Traveller's Diarrhoea
|
||
Completed |
NCT01902589 -
Resistance of Helicobacter Pylori to Antibiotics in Children
|
N/A | |
Not yet recruiting |
NCT04593368 -
Fecal Microbiome Transplantation (FMT) in Pediatric Patients Colonized With Antibiotic-resistant Pathogens Before Hematopoietic Stem Cell Transplantation (HSCT)
|
Phase 2 | |
Completed |
NCT03063437 -
A Trial of Encapsulated Fecal Microbiota for Vancomycin Resistant Enterococcus Decolonization
|
Phase 2 |