Evidence for Induction of Integron-Based Antibiotic Resistance by the SOS Response in a Clinical Setting

Bacterial resistance to β-lactams may rely on acquired β-lactamases encoded by class 1 integron-borne genes. Rearrangement of integron cassette arrays is mediated by the integrase IntI1. It has been previously established that integrase expression can be activated by the SOS response in vitro, leading to speculation that this is an important clinical mechanism of acquiring resistance. Here we report the first in vivo evidence of the impact of SOS response activated by the antibiotic treatment given to a patient and its output in terms of resistance development. We identified a new mechanism of modulation of antibiotic resistance in integrons, based on the insertion of a genetic element, the gcuF1 cassette, upstream of the integron-borne cassette blaOXA-28 encoding an extended spectrum β-lactamase. This insertion creates the fused protein GCUF1-OXA-28 and modulates the transcription, the translation, and the secretion of the β-lactamase in a Pseudomonas aeruginosa isolate (S-Pae) susceptible to the third generation cephalosporin ceftazidime. We found that the metronidazole, not an anti-pseudomonal antibiotic given to the first patient infected with S-Pae, triggered the SOS response that subsequently activated the integrase IntI1 expression. This resulted in the rearrangement of the integron gene cassette array, through excision of the gcuF1 cassette, and the full expression the β-lactamase in an isolate (R-Pae) highly resistant to ceftazidime, which further spread to other patients within our hospital. Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria

Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients

MODERN WP2 study group: Caroline Brossier, Elodie von Dach, Gesuele Renzi, Jacques Schrenzel, Stefanie Bunk, Siri Goepel, Florian Hölzl, Michael Eib, Ingo B.Autenrieth, Álvaro Pascual, Xavier Bertrand, Jelle Scharringa, Patrick Musicha.[Objectives] This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient.[Methods] Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis.[Results] We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3–14.1).[Conclusions] ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings.[Clinical study registration] German Clinical Trials Register, DRKS-ID: DRKS00013250.This study was part of a Joint Programming Initiative on Antimicrobial Resistance collaborative research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. AC681055), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1830) and Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03). As part of a separate research project, Marlieke de Kraker has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nos 115523, 115620 and 115737 (Combatting Bacterial Resistance in Europe projects (COMBACTE)), resources of which are composed of financial contribution from the European Union's 7th Framework Programme (FP7/2007±2013) and the European Federation of Pharmaceutical Industries and associations companies' in-kind contribution. Also, Elena Salamanca, Mercedes Delgado and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative Programme Intelligence Growth 2014-2020.Peer reviewe

High Prevalence of Mansonella perstans Filariasis in Rural Senegal.

Large parts of African and American countries are colonized by Mansonella, a very common but poorly described filarial nematode. Bloodsucking flies of the genus Culicoides are suspected to be the vector of Mansonella perstans, but no study in Senegal has confirmed that Culicoides can transmit the parasite. Designed specific real-time quantitative polymerase chain reaction (qPCR) can be used to identify microfilaria in stained blood smears. This study was performed in July and December 2010 in the southeastern Senegal, which is known to be endemic for M. perstans. We analyzed 297 blood smears from febrile and afebrile resident people by qPCR. The global prevalence of M. perstans was approximately 14.5% in both febrile and afebrile individuals. The age group of > 30 years had the highest prevalence (22.0%). No Culicoides among 1,159 studied specimens was positive for M. perstans and its vector in Senegal still requires identification

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Activité in vitro de la tigécycline vis-à-vis de 1234 souches bactériennes isolées au CHRU de Besançon, programme TEST 2004-2012

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Metronidazole increases the emergence of ciprofloxacin- and amikacin-resistant Pseudomonas aeruginosa by inducing the SOS response.

International audienc

Et après, qu’est-ce qui va changer ? Changements climatiques, biodiversité, santé humaine... ce que l’avenir pourrait nous réserver

National audienceDe quelques millions de personnes il y a 10 000 ans, la population humaine a atteint 1,7 milliard au début du XXe siècle et dépasse actuellement 7 milliards. La question de l’approvisionnement en nourriture, en eau et en énergie se pose de manière de plus en plus aiguë, avec des inégalités croissantes entre pays et à l’intérieur de chaque pays, qui sous-tendent la plupart des conflits actuels. Si tous les habitants de la planète avaient le standard de vie moyen des États-Unis ou de l’Australie, il faudrait plusieurs planètes pour couvrir l’ensemble de leurs besoins en ressources et en recyclage.Cette notion d’empreinte écologique conduit à la destruction d’écosystèmes majeurs qui hébergent une grande part d’une biodiversité mondiale en dégradation accélérée. La question se pose : comment enrayer puis inverser l’érosion de la biodiversité tout en pourvoyant aux besoins de l’humanité ? Dans le contexte du changement climatique, cette question sera abordée sous l’angle des impacts écologique mais aussi sanitaire : vagues de chaleur, diffusion des vecteurs de maladies transmissibles, bactéries qui deviennent résistantes aux antibiotiques et que l’on retrouve dans nos rivières, nos lacs, nos champs, et sont considérées comme des contaminants émergents

Rapid antibiotic susceptibility testing on blood cultures using MALDI-TOF MS.

Antibiotic resistance is a major public health problem requiring the early optimization of antibiotic prescriptions. Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) has been shown to accurately identify bacteria from positive blood culture. Here, we developed a rapid detection of Escherichia coli resistance to amoxicillin (AMX) and cefotaxime (CTX) from positive blood culture based on MALDI-TOF MS. Potential sparing of broad-spectrum antibiotics was also evaluated. We tested 103 E. coli-positive blood cultures. Blood cultures were subculture 1-hour in antibiotic-free rich liquid media before further incubation with and without AMX for 2.5 h or CTX for 2 h. Protein extracts associated with an internal control were spotted on a MALDI-TOF target and spectra were analyzed with the MBT-ASTRA prototype software (Bruker Daltonik GmbH, Bremen, Germany). Bacterial growth ratio was calculated from the AUC spectra obtained in the presence and absence of the antibiotic and compared to a threshold which classified E. coli as susceptible or resistant. Results were interpreted with MICs determined using agar dilution method as reference technique. MBT-ASTRA recognized 95% and 84% of the AMX- and CTX-susceptible isolates, respectively. Overall, quantitative analysis of mass spectra allows susceptibility testing within 4 hours after the positivity of blood culture with E. coli. At the first report of positive blood culture, MALDI-TOF MS would then provide the prescribers with the bacterial identification and the susceptibility to AMX and CTX, thus limiting the use of broad-spectrum compounds