Colistin, rifampicin, and meropenem administered as single agents in a model of pneumonia caused by a carbapenem-resistant Acinetobacter baumannii

International audienc

Observatoire Régional du Pneumocoque en région Pays de la Loire : résistance de Streptococcus pneumoniae aux antibiotiques en 2011

National audienc

Propriétés antibactériennes d’extraits de propolis contre des souches de Staphylococcus aureus sensibles ou résistantes à la méthicilline

La résistance aux antibiotiques est devenue l\u27un des problèmes majeurs de santé publique du XXIème siècle. Il existe donc un réel intérêt thérapeutique dans la recherche de composés ou d\u27extraits naturels capables de limiter cette résistance. La propolis est un mélange complexe composé de substances résineuses collectées par les abeilles sur différentes parties des plantes et arbres, de cires et de sécrétions salivaires de l\u27abeille. Elle sert principalement à colmater les interstices des parois de la ruche et comme véritable arme chimique contre les microorganismes. La propolis est utilisée depuis longtemps en médecine traditionnelle puisqu\u27elle possède des propriétés pharmacologiques intéressantes notamment antioxydante, anti-inflammatoire mais aussi antimicrobienne. Un échantillon de propolis, composé de 24 lots collectés en France (majoritairement dans le sud-ouest) en 2010 et 2011, a été extrait par différents solvants : EtOH 70%, MeOH, DCM et DCM/MeOH/eau 31/19/4 (mixte). La composition chimique des extraits a préalablement été déterminée au moyen d’analyses HPLC/DAD/MS et RMN 1H et 13C. L\u27activité antibactérienne a été évaluée sur des bactéries responsables d\u27infections nosocomiales, et plus spécifiquement sur 13 souches de Staphylococcus aureus [ATCC25923, six isolats cliniques de souches résistantes à la méthiciline (SARM) et six isolats cliniques de souches sensibles à la méthiciline (SASM)] par détermination de la concentration minimum d\u27inhibition (CMI) en milieu gélosé [1]. Les résultats ont montré que, parmi les quatre extraits, le DCM et le "mixte" présentaient une bonne activité antibactérienne contre S. aureus (SA) avec des CMI respectives de 60±10 et 67±15 µg/mL mais également sur quasiment toutes les souches SARM et SASM testées (CMI entre 30 et 97 µg/mL). Ces bonnes activités des extraits DCM et mixte peuvent être reliées à des teneurs élevées en polyphénols totaux et en flavonoïdes [1]. Diverses études ont en effet montré que ce type de mélange complexe, riche en polyphénols, était plus actif que les composés isolés les constituant. Les polyphénols agiraient ainsi de façon synergique, potentialisant l\u27activité antibactérienne de ces extraits [2]. D\u27autres études, menées in vitro, ont par ailleurs mis en évidence un réel synergisme entre propolis et antibiotiques [3], [4]. Ainsi, ces extraits de propolis présentent-ils un réel potentiel dans une lutte alternative contre des infections à staphylocoques.   Références [1]          S. Boisard et al., "Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis", Evid. Based Complement. Alternat. Med., vol. 2015, p. e319240, 2015. [2]          A. Kujumgiev, I. Tsvetkova, Y. Serkedjieva, V. Bankova, R. Christov, et S. Popov, "Antibacterial, antifungal and antiviral activity of propolis of different geographic origin", J. Ethnopharmacol., vol. 64, no 3, p. 235‑240, 1999. [3]          S. Stepanović, N. Antić, I. Dakić, et M. Švabić-Vlahović, "In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs", Microbiol. Res., vol. 158, no 4, p. 353‑357, 2003. [4]          A. Fernandes Júnior, E. C. Balestrin, J. E. C. Betoni, R. de O. Orsi, M. de L. R. de S. da Cunha, et A. C. Montelli, "Propolis: anti-Staphylococcus aureus activity and synergism with antimicrobial drugs", Mem. Inst. Oswaldo Cruz, vol. 100, no 5, p. 563‑566, 2005

Report of the laboratory confirmation of cases from the CDTUB Pobé, Benin

In 2009, 420 diagnostic samples (corresponding to 301 patients suspected of M. ulcerans infection) from the Centre de Dépistage et de Traitement de l’Ulcère de Buruli of Benin were subjected to IS2404 PCR at the Centre Hospitalier Universitaire of Angers. 180 samples (corresponding to 141 patients) were confirmed positive to M. ulcerans infection by PCR

M. ulcerans infection diagnosis by fine needle aspiration

Date du colloque&nbsp;: 04/2009</p

High throughput screening for identification of mycolactone targets : Relations between M. ulcerans and nervous system

Buruli ulcer is an infectious disease transmitted by arthropod vectors harboring Mycobacterium ulcerans, a mycobacterium which belong to the same family of bacteria causing tuberculosis and leprosy. The infection causes painless swelling and severe skin lesions. One key feature of M. ulcerans bacterium is its ability to secrete a necrotic toxin, the mycolactone within small lipophilic vesicles, which are critical for the bacterial induced cytotoxicity. The biological knowledge as well as the preventive and therapeutic means for this invalidating disease is still very limited.   Our first approach was to investigate whether the mycolactone toxin could be involved in the neutralization of pain by acting directly on the peripheral nervous system without causing destruction of nervous fibers. By use of live time fluorescence microscopy and appropriate markers, we showed that the addition of toxin at sub-toxic dose provokes modification of ionic currents of neuron cells. Based on this ability of the toxin, a molecular high throughput methodology was developed for the screening of a genome wide siRNA library and small molecules inhibitors to enable the search of the cellular targets for the toxin. The cell-based assay relies on automated confocal microscopy on macrophages coupled with dedicated image analysis. These two screening allowed us to identify a putative toxin target, and a toxin inhibitor. A binding assay confirmed that the putative target is a receptor of the toxin. Together these results allowed us to build a potential signaling pathway activated by the mycolactone and implicated in ionic channel activities.   The second approach was to confirm this model in the mouse model of M. ulcerans infection and its role in the hypoesthesia of the lesions. Toxin inhibitor, daily administered to mice, which were experimentally infected by M. ulcerans, conducted to the absence of the hypoesthesia of the lesions. Furthermore, a histological study of neuronal fibers did not show a destruction of neuronal cells. Moreover, in vitro studies have showed that M. ulcerans are able to colonize neuronal cells. Then, these results suggested that the hypoesthesia of the M. ulcerans lesions could be caused by a non-destructive process of nervous cells.

Discordance in the minimal inhibitory concentrations of ertapenem for Enterobacter cloacae: Vitek 2 system versus Etest and agar dilution methods

Our objective was to compare the ertapenem minimal inhibitory concentrations (MICs) for Enterobacter cloacae isolates categorized intermediate or resistant to ertapenem when measured with the Vitek 2 system, with the MICs for these isolates when measured by two methods performed in agar medium: the Etest and agar plate dilution method (APDM). Overall, 50 E. cloacae isolates were included in the study. The mean MIC of ertapenem was 2.92±1.77μg/ml according to the Vitek 2 system, 0.94±0.84μg/ml according to the Etest strips, and 0.93±0.62μg/ml according to the APDM. Furthermore, the MICs determined by the Vitek 2 system were higher than the MICs determined by the two other methods for 96% of strains. Lastly, according to the Etest strips and APDM, 42% of E. cloacae were susceptible to ertapenem. No carbapenemase was identified by the screening method used. Using the Vitek 2 system to determine ertapenem MICs for E. cloacae can have potential consequences in terms of additional carbapenemase-detecting tests and antimicrobial therapy. It would be interesting to determine if the Vitek 2 system is more effective for the detection of carbapenemase producers with low-level carbapenem resistance than the two methods performed in agar medium

Aromatic and Terpenic Compounds Loaded in Lipidic Nanocapsules: Activity against Multi-drug Resistant Acinetobacter baumannii Assessed in vitro and in a Murine Model of Sepsis.

Given the spread of multidrug resistance and the number of antibiotics in development, finding new antibacterial strategies becomes necessary. One of these strategies is to use extracts of essential oils that are a potential reservoir of effective antibacterial molecules. The objective of the study was to evaluate the possibility of administering to animal, mixtures of carvacrol and eugenol (phenols), cinnamaldehyde (aldehyde) and/or β-caryophyllene (alkene) encapsulated in lipid nanocapsules to provide an optimal bio distribution and antimicrobial efficacy. These suspensions were tested in vitro and the results showed an important antibacterial activity against A. baumannii, a multidrugresistant microorganism responsible for outbreaks in intensive care units, similar to the activity of non-encapsulated mixtures. Subsequently, the suspensions activities were assessed with a murine model of sepsis using the same A.Baumannii strain. These preliminary results showed a mice survival varying from 45% to 55%. It is the first time that antimicrobial essential oils can be administered intraperitonneally via nanomedicine. These results are encouraging and further studies are needed to pursue the development of this strategy