Impact of Cefotaxime and Ceftriaxone on the Emergence and Carrying of Multidrug-Resistant Bacteria
Impact of Cefotaxime and Ceftriaxone on the Emergence and Carrying of Multidrug-Resistant Bacteria
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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