Infection, BacterialCROCTXNCT03903783
Impact of Cefotaxime and Ceftriaxone on the Emergence and Carrying of Multidrug-Resistant Bacteria
A study testing Cefotaxime and Ceftriaxone in people with Infection, Bacterial, run by Fondation Hôpital Saint-Joseph at 1 site in France.
Trial summary
Among enterobacteria, the production of ESBL is the first cause of multidrug resistance. The first cases of ESBL-producing enterobacteriaceae (EBLSE) infections were described during the 1980s and subsequently experienced global spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Bacterial
- What is being tested?
- Cefotaxime and Ceftriaxone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteFrance
- Study dates
- 30 Apr 2019to 13 Aug 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient ≥ 18 years old
- Patient hospitalized in the department of internal medicine within the Hospital Group Paris Saint-Joseph
- Patient with probabilistic or documented C3G infection
- Patient affiliated to a social security scheme
- Francophone patient
- Patient living at home, in a nursing home or retirement home
- Patient able to give free, informed and express consent
Who cannot join
- Patient with allergy to cephalosporins
- Inclusion time greater than 24 hours after initiation of antibiotic therapy
- Patient having been hospitalized in the 3 months preceding the inclusion
- Patient who received antibiotic treatment within 3 weeks prior to inclusion
- Patient being included in another study
- Pregnant woman
- Patient under tutorship or curatorship
- Patient deprived of liberty
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Cefotaxime and Ceftriaxone on the Emergence and Carrying of Multidrug-Resistant Bacteria and Relationship to Residual Antibiotic Levels in Stool
Among enterobacteria, the production of ESBL is the first cause of multidrug resistance. The first cases of ESBL-producing enterobacteriaceae (EBLSE) infections were described during the 1980s and subsequently experienced global spread. Since the beginning of the century, the prevalence of EBLSE infections, especially among E. coli and K. pneumoniae, has increased dramatically. The emergence of multidrug-resistant enterobacteria is currently posing a real public health problem. The European antimicrobial resistance surveillance network evaluated, among clinical strains, the resistance rate for 3rd generation cephalosporins (C3G) at 9.5% for Escherichia coli and 28% for Klebsiella pneumoniae. The consequences of multidrug-resistant enterobacterial infections, which are mainly represented by ESBLs, are currently well known, both from the individual point of view (increase in mortality and length of hospital stay) and collective (increase of costs of care).
Data from the literature reveal an increased risk of ESBL bacteremia in patients with rectal carriage of ESBL-producing enterobacteria. The study by Goulenok et al. found as a risk factor for EBLSE bacteremia in patients known to be carriers at the rectal level the existence of antibiotic selection pressure and the presence of a urinary catheter. Woerther et al. have explained in their work that the digestive microbiota confers resistance to colonization by BMR. The impact of antibiotics on the latter leads to a probable rupture of this barrier and a loss of this resistance to colonization. In addition, each antibiotherapy does not impact the digestive microbiota equally and it seems that antibiotics with high anti-anaerobic activity or high biliary elimination are the most impacting. It is therefore essential, at a time of multidrug resistance, to focus on the influence of antibiotics on the digestive microbiota and the emergence and carriage of BMR.
Read more
Ceftriaxone and cefotaxime are two injectable injectable third-generation cephalosporins (C3G) commonly used in clinical practice. Despite their similar spectrum of action, it should be noted that they have substantially different pharmacokinetic properties, especially with regard to their half-life and their elimination routes (mainly urinary for cefotaxime, mixed: biliary and urinary for ceftriaxone). Some works have already been interested in this topic. Grohs et al. carried out a comparative study between ceftriaxone and cefotaxime on the emergence of AmpC hyperproducing enterobacteria (HL-CASE). This single-site study demonstrated that, at a hospital level, the preferential use of cefotaxime rather than ceftriaxone had collective and ecological benefits at the service level. Indeed, their results conclude that resistance development is weaker, as well as more limited carriage of HL-CASE Enterobacterial strains by replacing ceftriaxone with cefotaxime. It should be noted, however, that the modification of prescribing practices of C3G has been coupled with various measures to limit the emergence of AmpC hyperproductive enterobacteria (reinforcement of hygiene rules, awareness of the health care team at EBLSE, control of antibiotic ...).
In a context where the emergence of multidrug-resistant bacteria continues to increase, it seems appropriate to conduct a study to compare the impact of the use of ceftriaxone or cefotaxime on the emergence of BMR at the individual level. In the absence of a study clearly establishing the link between C3G types (ceftriaxone, cefotaxime) and the emergence of BMR and in line with the above research, this study aims to compare the microbiological impact of the use of either of these two C3Gs (in terms of emergence of bacterial resistance and impact on the diversity and quantity of digestive digestive bacteria). The study will have two periods: Period 1 during which patients hospitalized in the emergency department or in internal medicine and receiving C3G antibiotics will receive ceftriaxone, and the period 2 during which cefotaxime is cephalosporin used in first intention in these same patients.
Thus, this research project, by focusing on these 5 parameters in patients treated with ceftriaxone or cefotaxime, should make it possible to prove the influence of these antibiotherapies on the carriage of BMR (deleterious action on the diversity and the quantity of the intestinal bacterial flora, resulting in an increase in the relative fecal abundance of these BMRs promoting their carriage). In addition, the hypothesis is that, contrary to current data, cefotaxime is found at sufficiently high concentrations in the feces to have an impact on the microbiota equivalent to that of ceftriaxone, despite less significant biliary elimination.
This study therefore aims to compare their impacts on the microbiota and in particular on the emergence of multidrug-resistant bacteria (BMR) and enteropathogens such as Clostridium difficile.
- Conditions
- Infection, Bacterial
- Being tested
- Cefotaxime, Ceftriaxone
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefotaximeOther
Patients with C3G antibiotic therapy will receive cefotaxime. On the day of inclusion (T0, + 24 hours), a stool culture is performed on the first stool issued after the start of antibiotic therapy to detect BMR carriage and to evaluate the initial flora and fecal abundance initial relative in culturable multiresistant bacteria. In the absence of stool emission by the patient, an eswab rectal swab will be performed.
72 hours (± 24 hours, T1) after the start of antibiotic therapy, a stool sample will be taken and at the end of antibiotic therapy (+ 24 hours, T2) or during the oral relay to evaluate the modification of the initial flora and the relative fecal abundance of culturable multiresistant bacteria. In the case of "normal" transit (daily bowel movement), the bowel movement 72 hours after the start of antibiotic therapy will be analyzed. In the absence of stool emission by the patient, an eswab rectal swab will be performed.
CeftriaxoneOther
Patients with C3G antibiotic therapy will receive ceftriaxone. On the day of inclusion (T0, + 24 hours), a stool culture is performed on the first stool issued after the start of antibiotic therapy to detect BMR carriage and to evaluate the initial flora and fecal abundance initial relative in culturable multiresistant bacteria. In the absence of stool emission by the patient, an eswab rectal swab will be performed.
72 hours (± 24 hours, T1) after the start of antibiotic therapy, a stool sample will be taken and at the end of antibiotic therapy (+ 24 hours, T2) or during the oral relay to evaluate the modification of the initial flora and the relative fecal abundance of culturable multiresistant bacteria. In the case of "normal" transit (daily bowel movement), the bowel movement 72 hours after the start of antibiotic therapy will be analyzed. In the absence of stool emission by the patient, an eswab rectal swab will be performed.
| Study group | Role | What they receive |
|---|---|---|
| Cefotaxime | Active comparator | Not described Receives: Other: Cefotaxime |
| Ceftriaxone | Active comparator | Not described Receives: Other: Ceftriaxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Emergence of enterococci resistant to vancomycin
Measured: 24 Hours after the end of atnibiotherapy
Emergence of EBLSE
Measured: 24 Hours after the end of atnibiotherapy
Emergence of Clostridium difficile
Measured: 24 Hours after the end of atnibiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start30 Apr 2019
- Primary completion6 Jan 2020
- Study completion13 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infection, BacterialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benoit PILMIS, MD, Principal investigator, Fondation Hôpital Saint-Joseph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03903783
- Sponsor's protocol ID
- CROCTX
- Acronym
- CROCTX
- Status last verified
- Aug 2021
- First submitted
- 3 Apr 2019
- Last updated
- 16 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Cefotaxime and Ceftriaxone on the Emergence and Carrying of Multidrug-Resistant Bacteria and Relationship to Residual Antibiotic Levels in Stool
- ClinicalTrials.gov ID
- NCT03903783
- Acronym / sponsor ID
- CROCTX / CROCTX
- Conditions
- Infection, Bacterial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Study start
- 30 Apr 2019 (actual)
- Primary completion
- 6 Jan 2020 (actual)
- Study completion
- 13 Aug 2021 (actual)
- First posted
- 4 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Among enterobacteria, the production of ESBL is the first cause of multidrug resistance. The first cases of ESBL-producing enterobacteriaceae (EBLSE) infections were described during the 1980s and subsequently experienced global spread. Since the beginning of the century, the prevalence of EBLSE infections, especially among E. coli and K. pneumoniae, has increased dramatically. The emergence of multidrug-resistant enterobacteria is currently posing a real public health problem. The European antimicrobial resistance surveillance network evaluated, among clinical strains, the resistance rate for 3rd generation cephalosporins (C3G) at 9.5% for Escherichia coli and 28% for Klebsiella pneumoniae. The consequences of multidrug-resistant enterobacterial infections, which are mainly represented by ESBLs, are currently well known, both from the individual point of view (increase in mortality and length of hospital stay) and collective (increase of costs of care).
Data from the literature reveal an increased risk of ESBL bacteremia in patients with rectal carriage of ESBL-producing enterobacteria. The study by Goulenok et al. found as a risk factor for EBLSE bacteremia in patients known to be carriers at the rectal level the existence of antibiotic selection pressure and the presence of a urinary catheter. Woerther et al. have explained in their work that the digestive microbiota confers resistance to colonization by BMR. The impact of antibiotics on the latter leads to a probable rupture of this barrier and a loss of this resistance to colonization. In addition, each antibiotherapy does not impact the digestive microbiota equally and it seems that antibiotics with high anti-anaerobic activity or high biliary elimination are the most impacting. It is therefore essential, at a time of multidrug resistance, to focus on the influence of antibiotics on the digestive microbiota and the emergence and carriage of BMR.
Ceftriaxone and cefotaxime are two injectable injectable third-generation cephalosporins (C3G) commonly used in clinical practice. Despite their similar spectrum of action, it should be noted that they have substantially different pharmacokinetic properties, especially with regard to their half-life and their elimination routes (mainly urinary for cefotaxime, mixed: biliary and urinary for ceftriaxone). Some works have already been interested in this topic. Grohs et al. carried out a comparative study between ceftriaxone and cefotaxime on the emergence of AmpC hyperproducing enterobacteria (HL-CASE). This single-site study demonstrated that, at a hospital level, the preferential use of cefotaxime rather than ceftriaxone had collective and ecological benefits at the service level. Indeed, their results conclude that resistance development is weaker, as well as more limited carriage of HL-CASE Enterobacterial strains by replacing ceftriaxone with cefotaxime. It should be noted, however, that the modification of prescribing practices of C3G has been coupled with various measures to limit the emergence of AmpC hyperproductive enterobacteria (reinforcement of hygiene rules, awareness of the health care team at EBLSE, control of antibiotic ...).
In a context where the emergence of multidrug-resistant bacteria continues to increase, it seems appropriate to conduct a study to compare the impact of the use of ceftriaxone or cefotaxime on the emergence of BMR at the individual level. In the absence of a study clearly establishing the link between C3G types (ceftriaxone, cefotaxime) and the emergence of BMR and in line with the above research, this study aims to compare the microbiological impact of the use of either of these two C3Gs (in terms of emergence of bacterial resistance and impact on the diversity and quantity of digestive digestive bacteria). The study will have two periods: Period 1 during which patients hospitalized in the emergency department or in internal medicine and receiving C3G antibiotics will receive ceftriaxone, and the period 2 during which cefotaxime is cephalosporin used in first intention in these same patients.
Thus, this research project, by focusing on these 5 parameters in patients treated with ceftriaxone or cefotaxime, should make it possible to prove the influence of these antibiotherapies on the carriage of BMR (deleterious action on the diversity and the quantity of the intestinal bacterial flora, resulting in an increase in the relative fecal abundance of these BMRs promoting their carriage). In addition, the hypothesis is that, contrary to current data, cefotaxime is found at sufficiently high concentrations in the feces to have an impact on the microbiota equivalent to that of ceftriaxone, despite less significant biliary elimination.
This study therefore aims to compare their impacts on the microbiota and in particular on the emergence of multidrug-resistant bacteria (BMR) and enteropathogens such as Clostridium difficile.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cefotaxime | Active comparator | Other: Cefotaxime |
| Ceftriaxone | Active comparator | Other: Ceftriaxone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient ≥ 18 years old
- Patient hospitalized in the department of internal medicine within the Hospital Group Paris Saint-Joseph
- Patient with probabilistic or documented C3G infection
- Patient affiliated to a social security scheme
- Francophone patient
Key exclusion criteria (8 listed)
- Patient with allergy to cephalosporins
- Inclusion time greater than 24 hours after initiation of antibiotic therapy
- Patient having been hospitalized in the 3 months preceding the inclusion
- Patient who received antibiotic treatment within 3 weeks prior to inclusion
- Patient being included in another study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CefotaximePatients with C3G antibiotic therapy will receive cefotaxime. On the day of inclusion (T0, + 24 hours), a stool culture is performed on the first stool issued after the start of antibiotic therapy to detect BMR carriage and to evaluate the initial flora and fecal abundance initial relative in culturable multiresistant bacteria. In the absence of stool emission by the patient, an eswab rectal swab will be performed. 72 hours (± 24 hours, T1) after the start of antibiotic therapy, a stool sample will be taken and at the end of antibiotic therapy (+ 24 hours, T2) or during the oral relay to evaluate the modification of the initial flora and the relative fecal abundance of culturable multiresistant bacteria. In the case of "normal" transit (daily bowel movement), the bowel movement 72 hours after the start of antibiotic therapy will be analyzed. In the absence of stool emission by the patient, an eswab rectal swab will be performed. | Other | Cefotaxime |
| CeftriaxonePatients with C3G antibiotic therapy will receive ceftriaxone. On the day of inclusion (T0, + 24 hours), a stool culture is performed on the first stool issued after the start of antibiotic therapy to detect BMR carriage and to evaluate the initial flora and fecal abundance initial relative in culturable multiresistant bacteria. In the absence of stool emission by the patient, an eswab rectal swab will be performed. 72 hours (± 24 hours, T1) after the start of antibiotic therapy, a stool sample will be taken and at the end of antibiotic therapy (+ 24 hours, T2) or during the oral relay to evaluate the modification of the initial flora and the relative fecal abundance of culturable multiresistant bacteria. In the case of "normal" transit (daily bowel movement), the bowel movement 72 hours after the start of antibiotic therapy will be analyzed. In the absence of stool emission by the patient, an eswab rectal swab will be performed. | Other | Ceftriaxone |
Primary outcome
Emergence of enterococci resistant to vancomycin
Time frame: 24 Hours after the end of atnibiotherapy
Emergence of EBLSE
Time frame: 24 Hours after the end of atnibiotherapy
Emergence of Clostridium difficile
Time frame: 24 Hours after the end of atnibiotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benoit PILMIS, MD principal investigator
Fondation Hôpital Saint-Joseph
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cefotaxime and Ceftriaxone in people with Infection, Bacterial, run by Fondation Hôpital Saint-Joseph at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Emergence of enterococci resistant to vancomycin (time frame: 24 Hours after the end of atnibiotherapy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2021.