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Le Touquet – Paris-Plage, France

Fournier S.,Central Infection Control Team | Lepainteur M.,Central Infection Control Team | Kassis-Chikhani N.,Infection Control Unit | Huang M.,Central Infection Control Team | And 5 more authors.
Journal of Travel Medicine | Year: 2012

Assistance Publique-Hôpitaux de Paris launched a specific strategy to survey and control the spread of emerging multidrug-resistant bacteria such as carbapenemase-producing Enterobacteria (CPE). Among the 63 CPE events that occurred between 2004 and 2011, 87% involved patients with a link with cross-border exchanges, justifying the recommendation to screen and isolate such patients. © 2012 International Society of Travel Medicine.

Truffot-Pernot C.,University Pierre and Marie Curie | Veziris N.,University Pierre and Marie Curie | Veziris N.,Laboratoire Of Bacteriologie Hygiene
Revue des Maladies Respiratoires | Year: 2011

This review describes current developments for the bacteriological diagnosis of active tuberculosis. It deals mainly with molecular methods, describing their performance and how they can be integrated into more traditional diagnostic approaches. At present, microscopic examination and culture are still essential for the diagnosis of TB and to guide therapeutic decisions. Nucleic acid amplification and line probe assays speed up the identification and susceptibility testing of mycobacteria in AFB smear positive specimens or in culture. They are also efficient for comparison of M. tuberculosis strains with each other (genotyping). On the other hand, at present, molecular tests are not applicable for diagnosis in smear negative specimens and even less so for diagnosis of culture-negative tuberculosis. The use of serology for antibody/antigen detection is not useful and it is not appropriate to assays based on the release of interferon-γ release as they are currently available. Notable progress has been made but more sensitive diagnostic tests for TB are still urgently needed. © 2011 SPLF.

Ycart B.,University Grenoble alpes | Ycart B.,Laboratoire dExcellence TOUCAN Toulouse Cancer | Veziris N.,CNRS Immunology and Infectious Disease Center | Veziris N.,Laboratoire Of Bacteriologie Hygiene | Veziris N.,Colorado State University
PLoS ONE | Year: 2014

Estimation methods for mutation rates (or probabilities) in Luria-Delbrück fluctuation analysis usually assume that the final number of cells remains constant from one culture to another. We show that this leads to systematically underestimate the mutation rate. Two levels of information on final numbers are considered: either the coefficient of variation has been independently estimated, or the final number of cells in each culture is known. In both cases, unbiased estimation methods are proposed. Their statistical properties are assessed both theoretically and through Monte-Carlo simulation. As an application, the data from two well known fluctuation analysis studies on Mycobacterium tuberculosis are reexamined. © 2014 Ycart, Veziris.

Pantel A.,University Pierre and Marie Curie | Petrella S.,University Pierre and Marie Curie | Veziris N.,University Pierre and Marie Curie | Veziris N.,Laboratoire Of Bacteriologie Hygiene | And 10 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012

Fluoroquinolone (FQ) resistance is emerging in Mycobacterium tuberculosis. The main mechanism of FQ resistance is amino acid substitution within the quinolone resistance-determining region (QRDR) of the GyrA subunit of DNA gyrase, the sole FQ target in M. tuberculosis. However, substitutions in GyrB whose implication in FQ resistance is unknown are increasingly being reported. The present study clarified the role of four GyrB substitutions identified in M. tuberculosis clinical strains, two located in the QRDR (D500A and N538T) and two outside the QRDR (T539P and E540V), in FQ resistance. We measured FQ MICs and also DNA gyrase inhibition by FQs in order to unequivocally clarify the role of these mutations in FQ resistance. Wild-type GyrA, wild-type GyrB, and mutant GyrB subunits produced from engineered gyrB alleles by mutagenesis were overexpressed in Escherichia coli, purified to homogeneity, and used to reconstitute highly active gyrase complexes. MICs and DNA gyrase inhibition were determined for moxifloxacin, gatifloxacin, ofloxacin, levofloxacin, and enoxacin. All these substitutions are clearly implicated in FQ resistance, underlining the presence of a hot spot region housing most of the GyrB substitutions implicated in FQ resistance (residues NTE, 538 to 540). These findings help us to refine the definition of GyrB QRDR, which is extended to positions 500 to 540. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Veziris N.,University Pierre and Marie Curie | Veziris N.,Laboratoire Of Bacteriologie Hygiene | Truffot C.,University Pierre and Marie Curie | Mainardi J.-L.,University Pierre and Marie Curie | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Although beta-lactam antibiotics are not considered as antituberculous drugs, it has been recently shown that the combination of carbapenems and clavulanate is bactericidal in vitro. We evaluated in a murine model of tuberculosis the activity of carbapenems alone and combined with clavulanate against Mycobacterium tuberculosis. Swiss mice infected intravenously with 3 × 10 5 M. tuberculosis H37Rv were treated for 4 weeks with clavulanate alone or imipenem, meropenem, and ertapenem alone or combined with clavulanate, whereas a positive control group was treated with isoniazid, and a negative control group was held without treatment. The combination of imipenem or meropenem plus clavulanate significantly improved survival. Among groups of mice with 100% survival, only isoniazid reduced lung CFU counts; the carbapenem-clavulanate combinations did not prevent bacterial growth. Although less active than isoniazid, the combinations of imipenem or meropenem plus clavulanate improved the survival of mice infected with M. tuberculosis and should be further evaluated. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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