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OBJECTIVE: To assess the residual risk of waterborne contamination by Pseudomonas aeruginosa from a water network colonized by a single genotype [sequence type (ST) 299] despite the presence of antimicrobial filters in a medical intensive care unit (ICU). METHODS: During the first 19-month period since the ICU opened, contamination of the water network was assessed monthly by collecting water upstream of the filters. Downstream water was also sampled to assess the efficiency of the filters. P. aeruginosa isolates from patients were collected and compared with the waterborne ST299 P. aeruginosa by multiplex-rep polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. Cross-transmission events by other genotypes of P. aeruginosa were also assessed. RESULTS: Overall, 1.3% of 449 samples of filtered water were positive for P. aeruginosa in inoculum, varying between 1 and 104 colony-forming units/100 mL according to the tap. All P. aeruginosa hydric isolates belonged to ST299 and displayed fewer than two single nucleotide polymorphisms (SNPs). Among 278 clinical isolates from 122 patients, 10 isolates in five patients showed identical profiles to the hydric ST299 clone on both multiplex-rep PCR and PFGE, and differed by an average of fewer than five SNPs, confirming the water network reservoir as the source of contamination by P. aeruginosa for 4.09% of patients. Cross-transmission events by other genotypes of P. aeruginosa were responsible for the contamination of 1.75% of patients. DISCUSSION/CONCLUSION: Antimicrobial filters are not sufficient to protect patients from waterborne pathogens when the water network is highly contaminated. A microbiological survey of filtered water may be needed in units hosting patients at risk of P. aeruginosa infections, even when all water points-of-use are fitted with filters.
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Electroforesis en Gel de Campo Pulsado , Genotipo , Unidades de Cuidados Intensivos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Microbiología del Agua , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/clasificación , Humanos , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/transmisión , Filtración/instrumentación , Secuenciación Completa del Genoma , Tipificación Molecular , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Medición de RiesgoRESUMEN
OBJECTIVES: To evaluate the performances of the QMAC-dRAST GN (Gram-negative) kit for rapid antimicrobial sensitivity testing (AST) and two other methods, directly on positive blood-culture broth (PBCB), by comparison with a reference method: the MicroScan method based on broth microdilution on colonies isolated on PBCB subculture. METHODS: In total, 156 samples were collected prospectively from blood cultures positive for a Gram-negative rod. Each sample was tested with four AST techniques: (i) the QMAC dRAST GN kit, (ii) the disc diffusion (DD) method, (iii) the MicroScan method applied directly to PBCB; and (iv) MicroScan with isolates from PBCB subculture, as a reference. RESULTS: For 124 PBCB containing Enterobacterales, overall essential agreement (EA) and categorical agreement (CA) between the QMAC-dRAST on PBCB and the reference reached 95.7% and 93.5%, respectively. There were 3.0% very major errors (VME), 4.0% major errors (ME) and 2.8% minor errors (mE). A comparison of MicroScan on PBCB and the reference yielded 98.8% EA, 98.5% CA, and rates of 0.6% VME, 0.9% ME and 0.7% mE. The DD method on PBCB gave a CA of 95.8% and rates of 1.7% for VME, 2.0% for ME and 1.9% for mE. Results were obtained more rapidly for QMAC-dRAST (median of 6 h 37 min versus 18 h for the MicroScan and DD methods on PBCB). CONCLUSIONS: The QMAC-dRAST system provided rapid results well correlated with the reference method on PBCB containing Enterobacterales. Given the shorter time-to-results, the QMAC-dRAST system constitutes a fast and reliable alternative to conventional AST methods.
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Antibacterianos , Gammaproteobacteria , Pruebas de Sensibilidad Microbiana , Bacterias Gramnegativas , Factores de TiempoAsunto(s)
Farmacorresistencia Bacteriana Múltiple , Recto , Humanos , Recto/microbiología , Tamizaje Masivo , BacteriasRESUMEN
BACKGROUND: Three healthy volunteers carried similar quinolone-resistant E. coli (QREC) (pulsed field gel electrophoresis profiles) in their gut before and after 14 days ciprofloxacin treatment. Given the intensity of the selective pressure and the mutagenic properties of quinolones, we determined whether these strains had evolved at the phenotypic and/or genomic levels. MATERIAL AND METHODS: Commensal QREC from before day-0 (D0), and a month after 14 days of ciprofloxacin (D42) were compared in 3 volunteers. Growth experiments were performed; acetate levels, mutation frequencies, quinolone MICs and antibiotic tolerance were measured at D0 and D42. Genomes were sequenced and single nucleotide polymorphisms (SNPs) between D0 and D42 were analyzed using DiscoSNP and breseq methods. Cytoplasmic proteins were extracted, HPLC performed and proteins identified using X!tandem software; abundances were measured by mass spectrometry using the Spectral Counting (SC) and eXtraction Ion Chromatograms (XIC) integration methods. RESULTS: No difference was found in MICs, growth characteristics, acetate concentrations, mutation frequencies, tolerance profiles, phylogroups, O-and H-types, fimH alleles and sequence types between D0 and D42. No SNP variation was evidenced between D0 and D42 isolates for 2/3 subjects; 2 SNP variations were evidenced in one. At the protein level, very few significant protein abundance differences were identified between D0 and D42. CONCLUSION: No fitness, tolerance, metabolic or genomic evolution of commensal QREC was observed overtime, despite massive exposure to ciprofloxacin in the gut. The three strains behaved as if they had been unaffected by ciprofloxacin, suggesting that gut may act as a sanctuary where bacteria would be protected from the effect of antibiotics and survive without any detrimental effect of stress.
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Ciprofloxacina , Infecciones por Escherichia coli , Escherichia coli , Tracto Gastrointestinal/microbiología , Antibacterianos/farmacología , Ciprofloxacina/farmacología , Farmacorresistencia Bacteriana/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Fluoroquinolonas/farmacología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Context: Today, infective endocarditis (IE) caused by Enterococcus faecalis represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. Material and methods: To further study the in situ genetic microdiversity and its possible phenotypic manifestations in E. faecalis IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. Results: By sequencing a total of 58 E. faecalis genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors ebpA/B/C, and srtC, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the in-vitro phenotypic heterogeneity, growth, and early biofilm production. Conclusion: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses.
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Endocarditis Bacteriana/microbiología , Enterococcus faecalis/clasificación , Variación Genética , Infecciones por Bacterias Grampositivas/microbiología , Anciano , Anciano de 80 o más Años , Codón sin Sentido , Enterococcus faecalis/genética , Enterococcus faecalis/aislamiento & purificación , Femenino , Genoma Bacteriano , Válvulas Cardíacas/microbiología , Humanos , Masculino , Fenotipo , Eliminación de Secuencia , Secuenciación Completa del GenomaRESUMEN
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.
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Oftalmopatías , Síndrome de Stevens-Johnson , Corticoesteroides/uso terapéutico , Amnios , Oftalmopatías/etiología , Oftalmopatías/terapia , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/tratamiento farmacológicoRESUMEN
BACKGROUND: Escherichia coli bloodstream infections (BSIs) account for high mortality rates (5%-30%). Determinants of death are unclear, especially since the emergence of ESBL producers. OBJECTIVES: To determine the relative weight of host characteristics, bacterial virulence and antibiotic resistance in the outcome of patients suffering from E. coli BSI. METHODS: All consecutive patients suffering from E. coli BSI in seven teaching hospitals around Paris were prospectively included for 10 months. E. coli isolates were sequenced using Illumina NextSeq technology to determine the phylogroup, ST/ST complex (STc), virulence and antimicrobial resistance gene content. Risk factors associated with death at discharge or Day 28 were determined. RESULTS: Overall, 545 patients (mean ± SD age 68.5â±â16.5 years; 52.5% male) were included. Mean Charlson comorbidity index (CCI) was 5.6 (± 3.1); 19.6% and 12.8% presented with sepsis and septic shock, respectively. Portals of entry were mainly urinary (51.9%), digestive (41.9%) and pulmonary (3.5%); 98/545 isolates (18%) were third-generation cephalosporin resistant (3GC-R), including 86 ESBL producers. In-hospital death (or at Day 28) was 52/545 (9.5%). Factors independently associated with death were a pulmonary portal of entry [adjusted OR (aOR) 6.54, 95% CI 2.23-19.2, P = 0.0006], the iha_17 virulence gene (aOR 4.41, 95% CI 1.23-15.74, P = 0.022), the STc88 (aOR 3.62, 95% CI 1.30-10.09, P = 0.014), healthcare-associated infections (aOR 1.98, 95% CI 1.04-3.76, P = 0.036) and high CCI (aOR 1.14, 95% CI 1.04-1.26, P = 0.006), but not ESBL/3GC-R. CONCLUSIONS: Host factors, portal of entry and bacterial characteristics remain major determinants associated with mortality in E. coli BSIs. Despite a high prevalence of ESBL producers, antibiotic resistance did not impact mortality. (ClinicalTrials.gov identifier: NCT02890901.).
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Bacteriemia , Infecciones por Escherichia coli , Sepsis , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Escherichia coli/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Paris , Factores de Riesgo , Sepsis/tratamiento farmacológico , beta-Lactamasas/genéticaRESUMEN
BACKGROUND: Pseudomonas aeruginosa is a major bacterial pathogen responsible for hospital-acquired infections. Although its epidemiology is considered as non-clonal, certain international high-risk multidrug-resistant clones have been recognized. AIM: From the first report of an intra-hospital outbreak due to an SHV2a-producing P. aeruginosa strain, to describe the emergence of a new ST235-specific lineage harbouring this rare extended-spectrum ß-lactamase (ESBL). METHODS: Between May and October 2018, four patients hospitalized in the cardiovascular intensive care unit of a French teaching hospital were infected by a multidrug-resistant P. aeruginosa isolate. Serotype and antimicrobial susceptibility were tested; multi-locus sequence type (MLST), core genome MLST, and resistome were determined through whole genome sequencing. A phylogenetic analysis based on single nucleotide polymorphism was performed using available ST235 genomes. FINDINGS: The four strains were susceptible to colistin, ciprofloxacin, ceftazidime-avibactam, and ceftolozane-tazobactam. blaSHV2a was identified in each genome of this ST235-O11 serotype cluster that showed an identical cgMLST profile (0-2 out of 4162 different alleles). The phylogenic analysis of 162 ST235 genomes showed that only four other strains harboured a blaSHV2a, originating from France and USA, clustering together although being different from the outbreak strains. CONCLUSIONS: Among the ST235 P. aeruginosa strains, a sub-lineage sharing a common genetic background and harbouring the blaSHV2a ESBL seems to emerge from different locations, yielding secondary local outbreaks.
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Infección Hospitalaria/microbiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Proteínas Bacterianas/genética , Ceftazidima/farmacología , Cefalosporinas/farmacología , Ciprofloxacina/farmacología , Colistina/farmacología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Francia/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Tipificación de Secuencias Multilocus/métodos , Polimorfismo de Nucleótido Simple/genética , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/aislamiento & purificación , Tazobactam/farmacología , beta-Lactamasas/efectos de los fármacosAsunto(s)
Aldehído Oxidorreductasas/genética , Proteínas Bacterianas/genética , Endocarditis Bacteriana/microbiología , Enterococcus faecalis/genética , Genoma Bacteriano/genética , Infecciones por Bacterias Grampositivas/microbiología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/patología , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/aislamiento & purificación , Genotipo , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/patología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Recurrencia , Eliminación de Secuencia/genéticaAsunto(s)
Oftalmopatías/epidemiología , Trastornos Mentales/epidemiología , Enfermedades de la Uña/epidemiología , Síndrome de Stevens-Johnson/complicaciones , Adulto , Lentes de Contacto , Progresión de la Enfermedad , Oftalmopatías/etiología , Oftalmopatías/patología , Oftalmopatías/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Masculino , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Enfermedades de la Uña/etiología , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Esclerótica/patología , Piel/patología , Síndrome de Stevens-Johnson/psicologíaAsunto(s)
Oftalmopatías/diagnóstico , Ojo/inmunología , Pigmentación de la Piel/inmunología , Síndrome de Stevens-Johnson/complicaciones , Adolescente , Adulto , Anciano , Oftalmopatías/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndrome de Stevens-Johnson/inmunología , Adulto JovenRESUMEN
Plasmid prediction may be of great interest when studying bacteria of medical importance such as Enterobacteriaceae as well as Staphylococcus aureus or Enterococcus. Indeed, many resistance and virulence genes are located on such replicons with major impact in terms of pathogenicity and spreading capacities. Beyond strain outbreak, plasmid outbreaks have been reported in particular for some extended-spectrum beta-lactamase- or carbapenemase-producing Enterobacteriaceae. Several tools are now available to explore the 'plasmidome' from whole-genome sequences with various approaches, but none of them are able to combine high sensitivity and specificity. With this in mind, we developed PlaScope, a targeted approach to recover plasmidic sequences in genome assemblies at the species or genus level. Based on Centrifuge, a metagenomic classifier, and a custom database containing complete sequences of chromosomes and plasmids from various curated databases, PlaScope classifies contigs from an assembly according to their predicted location. Compared to other plasmid classifiers, PlasFlow and cBar, it achieves better recall (0.87), specificity (0.99), precision (0.96) and accuracy (0.98) on a dataset of 70 genomes of Escherichia coli containing plasmids. In a second part, we identified 20 of the 21 chromosomal integrations of the extended-spectrum beta-lactamase coding gene in a clinical dataset of E. coli strains. In addition, we predicted virulence gene and operon locations in agreement with the literature. We also built a database for Klebsiella and correctly assigned the location for the majority of resistance genes from a collection of 12 Klebsiella pneumoniae strains. Similar approaches could also be developed for other well-characterized bacteria.
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Genoma Bacteriano , Plásmidos/genética , Programas Informáticos , Cromosomas Bacterianos , Farmacorresistencia Bacteriana/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , Operón , Factores de Virulencia/genética , Secuenciación Completa del Genoma , Flujo de TrabajoRESUMEN
More than a century ago, Theodor Escherich isolated the bacterium that was to become Escherichia coli, one of the most studied organisms. Not long after, the strain began an odyssey and landed in many laboratories across the world. As laboratory culture conditions could be responsible for major changes in bacterial strains, we conducted a genome analysis of isolates of this emblematic strain from different culture collections (England, France, the United States, Germany). Strikingly, many discrepancies between the isolates were observed, as revealed by multilocus sequence typing (MLST), the presence of virulence-associated genes, core genome MLST, and single nucleotide polymorphism/indel analyses. These differences are correlated with the phylogeographic history of the strain and were due to an unprecedented number of mutations in coding DNA repair functions such as mismatch repair (MutL) and oxidized guanine nucleotide pool cleaning (MutT), conferring a specific mutational spectrum and leading to a mutator phenotype. The mutator phenotype was probably acquired during subculturing and corresponded to second-order selection. Furthermore, all of the isolates exhibited hypersusceptibility to antibiotics due to mutations in efflux pump- and porin-encoding genes, as well as a specific mutation in the sigma factor-encoding gene rpoS. These defects reflect a self-preservation and nutritional competence tradeoff allowing survival under the starvation conditions imposed by storage. From a clinical point of view, dealing with such mutator strains can lead microbiologists to draw false conclusions about isolate relatedness and may impact therapeutic effectiveness. IMPORTANCE Mutator phenotypes have been described in laboratory-evolved bacteria, as well as in natural isolates. Several genes can be impacted, each of them being associated with a typical mutational spectrum. By studying one of the oldest strains available, the ancestral Escherich strain, we were able to identify its mutator status leading to tremendous genetic diversity among the isolates from various collections and allowing us to reconstruct the phylogeographic history of the strain. This mutator phenotype was probably acquired during the storage of the strain, promoting adaptation to a specific environment. Other mutations in rpoS and efflux pump- and porin-encoding genes highlight the acclimatization of the strain through self-preservation and nutritional competence regulation. This strain history can be viewed as unintentional experimental evolution in culture collections all over the word since 1885, mimicking the long-term experimental evolution of E. coli of Lenski et al. (O. Tenaillon, J. E. Barrick, N. Ribeck, D. E. Deatherage, J. L. Blanchard, A. Dasgupta, G. C. Wu, S. Wielgoss, S. Cruveiller, C. Médigue, D. Schneider, and R. E. Lenski, Nature 536:165-170, 2016, https://doi.org/10.1038/nature18959) that shares numerous molecular features.
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INTRODUCTION: Sialendoscopy has changed the management of obstructive sialadenitis. Nowadays, minimally invasive techniques evolve to preserve salivary gland function. Intraductal lithotripsy allows stones fragmentation and retrieval without opening the salivary duct. We report our experience with the StoneBreaker (SB), a new lithotripter with improvement using a sterile bag that permits reuse of the SB without passing to sterilization. TECHNICAL NOTE: The non-sterilized SB was used into a sterile camera sleeve in 5 patients, 3 submandibular lithiases and 2 parotid lithiases. Technique and outcomes were described with a review of the literature. An explanatory video of the procedure was performed. DISCUSSION: Complete fragmentation was achieved and all fragments were extracted without any ductal damage. Utilization of the sterile sleeve did not change the SB efficiency and the procedure duration. The use of a sterile bag allowed several consecutive procedures with a single non-sterilized handpiece. However, the gas cartridge change may be more delicate when more than 80 impacts are needed. Patients remained symptoms and stones free one month after surgery.
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Aire Comprimido , Litotricia/instrumentación , Litotricia/métodos , Cálculos de las Glándulas Salivales/terapia , Desinfección , Endoscopía/instrumentación , Endoscopía/métodos , Humanos , Proyectos Piloto , Datos Preliminares , Estudios Retrospectivos , Conductos Salivales/diagnóstico por imagen , Conductos Salivales/patología , Cálculos de las Glándulas Salivales/complicaciones , Sialadenitis/etiología , Sialadenitis/terapiaRESUMEN
INTRODUCTION: The ameloblastic fibro-odontoma (FOA) is a rare benign tumor representing 1-3% of odontogenic tumors. The FOA affects young patients before the age of 20. Surgical treatment allows usually for recovery. Recurrence and malignant transformation are possible. OBSERVATION: A 3-year-old patient, with no medical and surgical history, was referred for a painless swelling of the right cheek progressing for several months. Radiographic examination showed a large mixed lesion. Buccal and lingual cortices were blown out. Surgical resection was performed under general anesthesia. Microscopically, the lesion consisted of dental tissue composed of mature dentin and enamel and of an epithelial component. These elements allowed for the diagnosis of ameloblastic fibro-odontoma. The postoperative course was uneventful. DISCUSSION: The management of this 3-year-old patient was delayed due to late consultation. The size of the lesion, that included all dental structures of sector 4, was big considering the very young age of the patient. The primary conservative surgical treatment allowed for preservation of teeth and of the inferior alveolar nerve, the only sequelae being the removal of the germ of the tooth no 44 directly involved in the tumor.
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Neoplasias Mandibulares/patología , Odontoma/patología , Preescolar , Femenino , Humanos , Neoplasias Mandibulares/cirugía , Odontoma/cirugíaRESUMEN
In neonatal intensive care units, topical agents represent an increasing part of the infection control armamentarium. Fifty-one coagulase-negative staphylococci (CNS) isolated from catheter-associated bloodstream infections in very preterm neonates were investigated in this study: 41.2% exhibited decreased susceptibility to at least one antiseptic (chlorhexidine 12%, benzalkonium 24%, acriflavine 33%) and 61% were resistant to mupirocin. QacA/B, mupA and both genes were detected by polymerase chain reaction in 59%, 63% and 49% of CNS, respectively. Seventy-six percent of Staphylococcus epidermidis (5/5 pulsed-field-gel electrophoresis subgroups) and 11% of Staphylococcus capitis (1/3 subgroups) were multi-resistant. Skin antisepsis using low-concentration aqueous formulations and off-label mupirocin indications should benefit from a stewardship programme.
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Antibacterianos/farmacología , Antiinfecciosos Locales/farmacología , Farmacorresistencia Bacteriana , Recien Nacido Extremadamente Prematuro , Mupirocina/farmacología , Infecciones Estafilocócicas/epidemiología , Staphylococcus/efectos de los fármacos , Bacteriemia/epidemiología , Bacteriemia/microbiología , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , ADN Bacteriano/genética , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Reacción en Cadena de la Polimerasa , Infecciones Estafilocócicas/microbiología , Staphylococcus/genética , Staphylococcus/aislamiento & purificaciónRESUMEN
A series of 10 dose confirmation studies was conducted to evaluate the persistent activity of an extended-release injectable (ERI) formulation of eprinomectin against single point challenge infections of gastrointestinal and pulmonary nematodes of cattle. The formulation, selected based on the optimal combination of high nematode efficacy, appropriate plasma profile, and satisfactory tissue residue levels, includes 5% poly(D,L-lactide-co-glycolic)acid (PLGA) and is designed to deliver eprinomectin at a dose of 1.0mg/kg bodyweight. Individual studies, included 16-30 cattle blocked based on pre-treatment bodyweight and randomly allocated to treatment with either ERI vehicle or saline (control), or the selected Eprinomectin ERI formulation. Treatments were administered once at a dose volume of 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder. In each study, cattle were challenged with a combination of infective stages of gastrointestinal and/or pulmonary nematodes 100, 120 or 150 days after treatment and were processed for parasite recovery according to standard techniques 25-30 days after challenge. Based on parasite counts, Eprinomectin ERI (1mg eprinomectin/kg bodyweight) provided >90% efficacy (p<0.05) against challenge with Cooperia oncophora and Cooperia surnabada at 100 days after treatment; against challenge with Ostertagia ostertagi, Ostertagia lyrata, Ostertagia leptospicularis, Ostertagia circumcincta, Ostertagia trifurcata, Trichostrongylus axei, and Cooperia punctata at 120 days after treatment; and against challenge with Haemonchus contortus, Bunostomum phlebotomum, Oesophagostomum radiatum and Dictyocaulus viviparus at 150 days after treatment. Results of a study to evaluate eprinomectin plasma levels in cattle treated with the Eprinomectin ERI formulation reveal a characteristic second plasma concentration peak and a profile commensurate with the duration of efficacy. These results confirm that the Eprinomectin ERI formulation can provide high levels of parasite control against a range of nematodes of cattle for up to 5 months following a single treatment.
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Antinematodos/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Ivermectina/análogos & derivados , Infecciones por Nematodos/veterinaria , Animales , Antinematodos/sangre , Antinematodos/farmacocinética , Bovinos , Femenino , Inyecciones , Ivermectina/sangre , Ivermectina/farmacocinética , Ivermectina/uso terapéutico , Masculino , Nematodos/fisiología , Infecciones por Nematodos/tratamiento farmacológico , Distribución Aleatoria , Factores de TiempoRESUMEN
The therapeutic efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against induced infections of developing fourth-stage larval or adult gastrointestinal and pulmonary nematodes of cattle in a series of six studies under two identical protocols (three each for developing fourth-stage larvae or adults) conducted in the USA, Germany or the UK (two studies at each location, one per stage). Each study initially included 16 nematode-free cattle. The cattle were of various breeds or crosses, weighed 109-186.5 kg prior to treatment, and were approximately 4-7 months old. The animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: eprinomectin ERI vehicle (control) at 1 mL/50 kg body weight or eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of eight and eight animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, cattle were infected with a combination of infective third-stage larvae or eggs of gastrointestinal and pulmonary nematodes. Inoculation was scheduled so that the nematodes were expected to be fourth-stage larvae or adults at the time of treatment. For parasite recovery, all study animals were humanely euthanized and necropsied 14-15 (adult infections) or 21-22 days after treatment (developing fourth-stage larval infections). When compared with the vehicle-treated control counts, efficacy of eprinomectin ERI against developing fourth-stage larvae and adults was ≥98% (p<0.05) for the following nematodes: Dictyocaulus viviparus, Bunostomum phlebotomum, Cooperia curticei, C. oncophora, C. surnabada, C. punctata, Haemonchus contortus, H. placei, Nematodirus helvetianus, Oesophagostomum radiatum, Oes. venulosum, Ostertagia leptospicularis, O. ostertagi, O. circumcincta, O. pinnata, O. trifurcata (developing fourth-stage larval infections only), Strongyloides papillosus, Trichostrongylus axei, T. colubriformis, and Trichuris ovis (adult infections only). All animals accepted the treatment well. No adverse reaction to treatments was observed in any animal in any study.
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Antinematodos/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Ivermectina/análogos & derivados , Infecciones por Nematodos/veterinaria , Animales , Antinematodos/administración & dosificación , Bovinos , Enfermedades de los Bovinos/parasitología , Femenino , Inyecciones , Ivermectina/administración & dosificación , Ivermectina/uso terapéutico , Larva , Masculino , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/parasitología , Distribución Aleatoria , Resultado del TratamientoRESUMEN
Although discordant phenotypes in monozygotic twins with developmental disorder are not an exception, underlying genetic discordance is rarely reported. Here, we report on the clinical and cytogenetic details of 4-year-old female monozygotic twins with discordant phenotypes. Twin 1 exhibited global developmental delay, overweight and hyperactivity. Twin 2 had an autistic spectrum disorder. Molecular karyotyping in twin 1 identified a 2p25.3 deletion, further confirmed by Fluorescence in situ hybridization (FISH) analysis on leukocytes. Interestingly, array comparative genomic hybridization was normal in twin 2 but FISH analysis using the same probe as twin 1 showed mosaicism with one-third of cells with a 2p25.3 deletion, one-third of cells with a 2p25.3 duplication, and one-third of normal cells. Genotyping with microsatellite markers confirmed the monozygosity of the twins. We propose that the chromosome imbalance may be due to a mitotic non-allelic recombination occurring during blastomeric divisions of a normal zygote. Such event will result in three distinct cell populations, whose proportion in each embryo formed after separation from the zygote may differ, leading to discordant chromosomal anomalies between twins. We also discuss that the MYTL1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins.
Asunto(s)
Trastorno Autístico/genética , Cromosomas Humanos Par 2 , Discapacidades del Desarrollo/genética , Enfermedades en Gemelos/genética , Proteínas de la Membrana/genética , Mosaicismo , Proteínas Musculares/genética , Proteínas del Tejido Nervioso/genética , Factores de Transcripción/genética , Gemelos Monocigóticos/genética , Trastorno Autístico/fisiopatología , Preescolar , Hibridación Genómica Comparativa , Discapacidades del Desarrollo/fisiopatología , Enfermedades en Gemelos/fisiopatología , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Fenotipo , Recombinación GenéticaRESUMEN
BACKGROUND: Deletions of chromosome 19 have rarely been reported, with the exception of some patients with deletion 19q13.2 and Blackfan-Diamond syndrome due to haploinsufficiency of the RPS19 gene. Such a paucity of patients might be due to the difficulty in detecting a small rearrangement on this chromosome that lacks a distinct banding pattern. Array comparative genomic hybridisation (CGH) has become a powerful tool for the detection of microdeletions and microduplications at high resolution in patients with syndromic mental retardation. METHODS AND RESULTS: Using array CGH, this study identified three interstitial overlapping 19q13.11 deletions, defining a minimal critical region of 2.87 Mb, associated with a clinically recognisable syndrome. The three patients share several major features including: pre- and postnatal growth retardation with slender habitus, severe postnatal feeding difficulties, microcephaly, hypospadias, signs of ectodermal dysplasia, and cutis aplasia over the posterior occiput. Interestingly, these clinical features have also been described in a previously reported patient with a 19q12q13.1 deletion. No recurrent breakpoints were identified in our patients, suggesting that no-allelic homologous recombination mechanism is not involved in these rearrangements. CONCLUSIONS: Based on these results, the authors suggest that this chromosomal abnormality may represent a novel clinically recognisable microdeletion syndrome caused by haploinsufficiency of dosage sensitive genes in the 19q13.11 region.