Impact of exposure of methicillin-resistant Staphylococcus aureus to polyhexanide in vitro and in vivo.

Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increase the need to develop alternative decolonization molecules. The absence of reported adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as topical antiseptic. In the present study we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced-susceptibility to polyhexanide by prolonged-stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes, and with concomitant decreased susceptibility to daptomycin and other cell-wall active antibiotics. However, the in vitro emergence of reduced-susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine antiseptic. During in vivo polyhexanide clinical decolonization treatment, neither polyhexanide reduced-susceptibility nor chlorhexidine cross-resistance were observed. Together, these observations suggest that polyhexanide could be used safely for decolonisation of carriers of chlorhexidine-resistant S. aureus strains but highlight the need for careful use of polyhexanide at low antiseptic concentrations

Clonal diversity and detection of carbapenem resistance encoding genes among multidrug-resistant Acinetobacter baumannii isolates recovered from patients and environment in two intensive care units in a Moroccan hospital

Background Carbapenem-resistant Acinetobacter baumannii has recently been defined by the World Health Organization as a critical pathogen. The aim of this study was to compare clonal diversity and carbapenemase-encoding genes of A. baumannii isolates collected from colonized or infected patients and hospital environment in two intensive care units (ICUs) in Morocco. Methods The patient and environmental sampling was carried out in the medical and surgical ICUs of Mohammed V Military teaching hospital from March to August 2015. All A. baumannii isolates recovered from clinical and environmental samples, were identified using routine microbiological techniques and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Antimicrobial susceptibility testing was performed using disc diffusion method. The carbapenemase-encoding genes were screened for by PCR. Clonal relatedness was analyzed by digestion of the DNA with low frequency restriction enzymes and pulsed field gel electrophoresis (PFGE) and the multi locus sequence typing (MLST) was performed on two selected isolates from two major pulsotypes. Results A total of 83 multidrug-resistant A. baumannii isolates were collected: 47 clinical isolates and 36 environmental isolates. All isolates were positive for the bla OXA51-like and bla OXA23-like genes. The coexistence of bla NDM-1 /bla OXA-23-like and bla OXA 24-like /bla OXA-23-like were detected in 27 (32.5%) and 2 (2.4%) of A. baumannii isolates, respectively. The environmental samples and the fecally-colonized patients were significantly identified (p < 0.05) as the most common sites of isolation of NDM-1-harboring isolates. PFGE grouped all isolates into 9 distinct clusters with two major groups (0007 and 0008) containing up to 59% of the isolates. The pulsotype 0008 corresponds to sequence type (ST) 195 while pulsotype 0007 corresponds to ST 1089.The genetic similarity between the clinical and environmental isolates was observed in 80/83 = 96.4% of all isolates, belonging to 7 pulsotypes. Conclusion This study shows that the clonal spread of environmental A. baumannii isolates is related to that of clinical isolates recovered from colonized or infected patients, being both associated with a high prevalence of the bla OXA23-like and bla NDM-1genes. These findings emphasize the need for prioritizing the bio-cleaning of the hospital environment to control and prevent the dissemination of A. baumannii clonal lineages

French database of children and adolescents with Prader-Willi syndrome

<p>Abstract</p> <p>Background</p> <p>Prader-Willi syndrome (PWS) is a rare multisystem genetic disease leading to severe complications mainly related to obesity. We strongly lack information on the natural history of this complex disease and on what factors are involved in its evolution and its outcome. One of the objectives of the French reference centre for Prader-Willi syndrome set-up in 2004 was to set-up a database in order to make the inventory of Prader-Willi syndrome cases and initiate a national cohort study in the area covered by the centre.</p> <p>Description</p> <p>the database includes medical data of children and adolescents with Prader-Willi syndrome, details about their management, socio-demographic data on their families, psychological data and quality of life of the parents. The tools and organisation used to ensure data collection and data quality in respect of good clinical practice procedures are discussed, and main characteristics of our Prader-Willi population at inclusion are presented.</p> <p>Conclusion</p> <p>this database covering all the aspects of PWS clinical, psychological and social profiles, including familial psychological and quality of life will be a powerful tool for retrospective studies concerning this complex and multi factorial disease and could be a basis for the design of future prospective multicentric studies. The complete database and the Stata.do files are available to any researcher wishing to use them for non-commercial purposes and can be provided upon request to the corresponding author.</p

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

Molecular characterization of carbapenem-resistant Gram-negative bacilli clinical isolates in Algeria

Nadjette Bourafa,1&ndash;3 Wafaa Chaalal,1,4 Sofiane Bakour,1 Rym Lalaoui,1 Nafissa Boutefnouchet,2 Seydina M Diene,1 Jean-Marc Rolain1 1Aix Marseille Universite, MEPHI, IHU-Mediterranee Infection, Marseille, France; 2Laboratoire de Microbiologie et Biochimie Appliqu&eacute;e, D&eacute;partement de Biochimie, Facult&eacute; des Sciences, Universit&eacute; Badji Mokhtar Annaba, Algeria; 3D&eacute;partement de Biologie, Facult&eacute; des Sciences de la Nature et de la Vie, Universit&eacute; Mohamed Cherif Messaadia-Souk-ahras, Algeria; 4Laboratoire de Microbiologie Appliqu&eacute;e, Facult&eacute; des Sciences de la Nature et de la Vie, Universit&eacute; d&rsquo;Oran, Es Senia, Oran, Algeria Objectives: The aims of this study were to investigate the occurrence of carbapenem-resistant Gram-negative bacilli (GNB) isolated from inpatients and outpatients in Algeria between July and September 2015, and to screen their resistance mechanisms and genetic relatedness.Materials and methods: A total of 68 non-redundant isolates were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) antibiotic susceptibility testing was performed using disk diffusion and Etest methods. Carbapenemase activity was carried out using modified Carba NP test, EDTA assay, and the modified Hodge test. Molecular characterization of carbapenemases and extended-spectrum &beta;-lactamase (ESBL) genes were detected by standard PCR and sequencing. Genotyping of carbapenem-resistant isolates was performed by multilocus sequence typing (MLST) analysis.Results: Of the 68 GNB isolates, 13 (19%) showed reduced susceptibility to carbapenems, including, four Klebsiella pneumoniae, one Escherichia coli, six Acinetobacter baumannii, and two Pseudomonas aeruginosa. blaOXA-48 gene was detected in the five Enterobacteriaceae isolates, and blaOXA-23 was identified in all A. baumannii isolates. OprD mutations were revealed in the two P. aeruginosa isolates. A total of 11 out of the 13 carbapenem-resistant GNB were detected in inpatients, and the two remaining strains were isolated from outpatients. Molecular typing showed the presence of four sequence types (STs) among the OXA-48-producing K.&nbsp;pneumoniae isolates: ST101, ST147, ST163, and ST2017. ST533 was identified for the OXA-48 producing E. coli isolate. All of the A. baumannii and P. aeruginosa were assigned to the international clonal lineages ST2 and ST654, respectively.Conclusion: This study reports the first detection of the epidemic multidrug-resistant lineage, K. pneumoniae ST147 coproduced blaOXA-48 and ESBL genes in Algeria and represents the first description of OXA-48-producing E. coli ST533 and K. pneumoniae ST163 and ST2017. In addition, this study describes for the first time the emergence of OXA-48-producing E. coli and K. pneumoniae in the community in Algeria, leading to major problems for managing microbial infections. Keywords: Gram-negative bacilli, carbapenem resistance, epidemic lineages, Algeri