Clinical 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. 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.