Highlighted publications

Three or four of each year's publications are highlighted below.

For a complete list of the MiHAR Lab publications (2011-2015), including those of new members before they joined the Group, click here.


Year 2015

Chemotherapy-driven Dysbiosis in the Intestinal Microbiome

Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, Moreau P, Potel G, De La Cochetiere MF, Batard E, Knights D. Aliment Pharmacol Ther 2015;42:515-528.

Data have been collected in France during Emmanuel Montassier's PhD scholarship. Bioinformatics and statistical analyses have been deepened during his post-doctoral stay in Dan Knights Lab at the University of Minnesota Minneapolis. Although this study does not focus on antibiotics and bacterial resistance, it shows that the lab now masters powerful tools to study the role of intestinal microbiota in bacterial resistance (including network analysis and the computational prediction of the metagenome functional composition) . Other exciting results from this cohort are currently submitted for publication.


Systematic analysis of the relationship between antibiotic use and extended-spectrum beta-lactamase resistance in Enterobacteriaceae in a French hospital: a time series analysis.

Vibet MA, Roux J, Montassier E, Corvec S, Juvin ME, Ngohou C, Lepelletier D, Batard E. Eur J Clin Microbiol Infect Dis 2015; DOI 10.1007/s10096-015-2437-3

Combining data from the Microbiology lab, Pharmacy and Hospital Information System, we explored the relationship between antibiotic use and ESBL mediated resistance in nosocomial isolates of Enterobacteriaceae. As we suspected it from a previous litterature analysis, we did not find amoxicilin or amoxicillin-clavulanate to be linked with ESBL incidence, although 3rd and 4th generation cephalosporins and fluoroquinolones were. These results encourage us to compare the ecological effects of penicillins, cephalosporins and fluoroquinolones on the intestinal microbiota. Furthermore, our systematic analysis showed that ESBL resistance was linked to tetracycline use. This result is in line with a previous study where we found tetracyclines to be more used in hospitals with the highest rates of fluoroquinolone resistant Escherichia coli. Further works will be conducted on the impact of tetracycline use on cephalosporin and fluoroquinolone resistance.


Elaboration of a consensual definition of de-escalation allowing a ranking of beta-lactams.

Weiss E, Zahar JR, Lesprit P, Ruppe E, Leone M, Chastre J, Lucet JC, Paugam-Burtz C, Brun-Buisson C, Timsit JF. Clin Microbiol Infect 2015; 21 : 649.e1-649.e10.

Before joining the MiHAR Lab, Jean-Ralph Zahar co-authored this study which intended to rank beta-lactam antibiotics according to both their spectra and their potential to promote selective pressure. The consensus was reached through modified Delphi method involving French experts in the field of intensive care, infectious diseases and clinical microbiology. Interestingly, experts ranked amoxicillin-clavulanate and 3rd-generation cephalosporins in distinct positions (respectively #2 and #3). These results complete the list of critical antibiotics particularly prone to select bacterial resistance, that the French Agency Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) issued in 2013, and that included indiscriminately amoxicillin-clavulanate and 3rd-generation cephalosporins. Hence, this study reinforces our hypothesis that amoxicillin-clavulanate should be prefered to cephalosporins and fluoroquinolones for the empirical therapy of community-acquired lower respiratory tract infection. Our future experimental and clinical studies should help to confirm and complete this classification.


Challenges of controlling a large outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae in a French university hospital.

Semin-Pelletier B, Cazet L, Bourigault C, Juvin ME, Boutoille D, Raffi F, Hourmant M, Blancho G, Agard C, Connault J, Corvec S, Caillon J, Batard E, Lepelletier D. J Hosp Infect 2015; 89(4): 248-53.

This paper describes the incomplete success and high costs of control measures in a large outbreak of Carbapenemase-producing Klebsiella pneumoniae in Centre Hospitalier Universitaire de Nantes. Further works are currently conducted to understand the dynamics of this outbreak. Personalised control measures that we explore in the MiHAR Lab may help us to be more efficient and cost-effective when we face the next epidemics.


Year 2014


Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis - current evidence and potential clinical applications.

Touchefeu Y, Montassier E, Nieman K, Gastinne T, Potel G, Bruley des Varannes S, Le Vacon F, de La Cochetiere MF. Aliment Pharmacol Ther 2014; 40(5): 409-21

This paper reviewed the role of chemotherapy-induced alterations of the intestinal microbiota in mucositis. Future works will have to describe the interaction between antineoplastic chemotherapy, intestinal microbiota, the host mucosa and intestinal carriage of resistant bacteria.


Prolonged hospital stay, an adverse effect of strict national policy for controlling the spread of highly resistant microorganisms.

Birgand G, Schwarzinger M, Perozziello A, Lolom I, Pelat C, Armand-Lefevre L, Buzzi JC, Andremont A, Yazdanpanah Y, Lucet JC. Infect Control Hosp Epidemiol 2014; 35(11): 1427-9.

Before joining the MiHAR Lab, Gabriel Birgand showed that infection control measures for controlling the spread of Highly Resistant Organisms (HRO, including Carbapanemase Producing Enterobacteriaceae and Glycopeptide Resistant Enterococci) resulted in a great and highly significant increase of Length of Stay (LOS), from 21days in HRO-negative patients to 45 days in HRO-positive patients. Current infection control measures are resource-consuming, and they have to be optimized. Personalised strategies, based on host characteristics, antibacterial therapy and intestinal microbiota composition may help to decrease the burden of infection control measures.


16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation.

Montassier E, Batard E, Massart S, Gastinne T, Carton T, Caillon J, Le Fresne S, Caroff N, Hardouin JB, Moreau P, Potel G, Le Vacon F, de La Cochetiere MF. Microb Ecol 2014; 67(3): 690-9

This is the first Lab publication where we used High-Throughput 454 DNA Pyrosequencing for analysis, and the QIIME tools for bioinformatics. Here, we detailed the alterations of the intestinal microbiota, in non-Hodgkin's lymphoma patients undergoing bone marrow transplantation conditioning treatment. Microbiota diversity was decreased, and more than 50 taxa varied significantly between the prechemotherapy and postchemotherapy samples.


Increasing use of third-generation cephalosporins for pneumonia in the emergency department: may some prescriptions be avoided?

Goffinet N, Lecadet N, Cousin M, Peron C, Hardouin JB, Batard E, Montassier E. Eur J Clin Microbiol Infect Dis 2014; 33(7): 1095-9

Third-generation cephalosporins, as well as fluoroquinolones, are particularly prone to select resistance in Enterobacteriaceae. In a previous work based on quantities of antibiotics that were delivered by the hospital pharmacy , we showed that the use of 3rd-generation cephalosporins dramatically increased in the Emergency Department between 2002 and 2012, from 9.7% of total antibiotic use to 22.6% (estimate per year,+1.2±0.2%) [Montassier E, Corvec S, Hardouin JB, Potel G, Batard E. Use of fluoroquinolones and third-generation cephalosporins in the emergency department: an 11-year survey. Eur J Emerg Med 2014; 21(6): 442-6]. In this study, by reviewing patient charts, we observed a similar increase in patients treated in the ED for a community-acquired pneumonia, from 13.9 % of patients in 2002 to 29.5 % in 2012. This increase was independent from illness severity, comorbidities and previous antibacterial therapy. Moreover, we estimated that the 3rd-generation cephalosporin was avoidable - i.e. could have been replaced by an antibiotic less prone to select bacterial resistance, like an aminopenicillin -  in 80 % of patients. Since this work, we completed this study with a multicentric investigation, where we found that the proportion of patients treated with a 3rd-generation cephalosporin or a fluoroquinolone was highly variable among EDs [Batard E, Lecadet N, Goffinet N, Hardouin JB, Group TCS, Lepelletier D, Potel G, Montassier E. High variability among Emergency Departments in 3rd-generation cephalosporins and fluoroquinolones use for community-acquired pneumonia. Infection 2015]. Taken together, these results show that 3rd-generation cephalosporins, as well as fluoroquinolones, are overused in ED patients treated for a community-acquired pneumonia, with potential increased risk of intestinal carriage and secondary infection of ESBL producing Enterobacteriaceae.