Genome-Scale Identification Method Applied to Find Cryptic Aminoglycoside Resistance Genes in Pseudomonas aeruginosa

BACKGROUND:The ability of bacteria to rapidly evolve resistance to antibiotics is a critical public health problem. Resistance leads to increased disease severity and death rates, as well as imposes pressure towards the discovery and development of new antibiotic therapies. Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology. RESULTS:We have applied a new genomic method, Scalar Analysis of Library Enrichments (SCALEs), to identify genomic regions that, given increased copy number, may lead to aminoglycoside resistance in Pseudomonas aeruginosa at the genome scale. We report the result of selections on highly representative genomic libraries for three different aminoglycoside antibiotics (amikacin, gentamicin, and tobramycin). At the genome-scale, we show significant (p<0.05) overlap in genes identified for each aminoglycoside evaluated. Among the genomic segments identified, we confirmed increased resistance associated with an increased copy number of several genomic regions, including the ORF of PA5471, recently implicated in MexXY efflux pump related aminoglycoside resistance, PA4943-PA4946 (encoding a probable GTP-binding protein, a predicted host factor I protein, a delta 2-isopentenylpyrophosphate transferase, and DNA mismatch repair protein mutL), PA0960-PA0963 (encoding hypothetical proteins, a probable cold shock protein, a probable DNA-binding stress protein, and aspartyl-tRNA synthetase), a segment of PA4967 (encoding a topoisomerase IV subunit B), as well as a chimeric clone containing two inserts including the ORFs PA0547 and PA2326 (encoding a probable transcriptional regulator and a probable hypothetical protein, respectively). CONCLUSIONS:The studies reported here demonstrate the application of new a genomic method, SCALEs, which can be used to improve understanding of the evolution of antibiotic resistance in P. aeruginosa. In our demonstration studies, we identified a significant number of genomic regions that increased resistance to multiple aminoglycosides. We identified genetic regions that include open reading frames that encode for products from many functional categories, including genes related to O-antigen synthesis, DNA repair, and transcriptional and translational processes

Aging as a predictor of nursing workload in Intensive Care Unit: results from a Brazilian Sample

OBJECTIVE Verify if aging is an independent predictor of NW in ICU, according to age groups, and its predictive value as a determinant of NW in ICU. METHODS Study was conducted from 2012 to 2016. A convenience sample composed by patients (age ≥ 18) admitted to nine ICU belonging to a Brazilian hospital, was analyzed. Age was assumed as an independent variable and NW (measured by the Nursing Activities Score - NAS) as dependent. Linear regression model and ROC curve were used for the analysis. RESULTS 890 participants (361 older people), mostly males (58.1%). The mean NAS score was higher among older participants in comparison to adults (p=0.004) but not within categories of aging (p=0.697). Age was responsible for 0.6% of NAS score. Each year of age increases NAS score in 0.081 points (p=0.015). However, age was not a good predictor of NAS score (AUC = 0.394; p=0.320). CONCLUSION The care of older people in ICU is associated with an increase in NW, compared to adults. Aging can be considered an associated factor but not a good predictor of NW in ICU.OBJETIVO Verificar si el envejecimiento es un predictor independiente de la Carga de Trabajo de Enfermería (CTE) en la Unidad de Cuidados Intensivos (UCI), según grupos etarios y su valor predictivo como determinante de la CTE en la UCI. MÉTODOS Se analizó una muestra de conveniencia compuesta por pacientes (edad ≥ 18) ingresados en nueve UCI pertenecientes a un hospital brasileño. La edad se asumió como variable independiente y como variable dependiente la carga de trabajo de enfermería -medida por el sistema Nursing Activities Score (NAS) de puntuación de actividades de enfermería. Para el análisis, se utilizaron el modelo de regresión lineal y la curva ROC. RESULTADOS 890 participantes (361 adultos mayores), en su mayoría varones (58,1%). La puntuación NAS promedio fue mayor entre los participantes adultos mayores en comparación con los adultos (p=0,004), pero no en las categorías de envejecimiento (p=0,697). La edad fue responsable del 0,6% de la puntuación NAS. Cada año de edad aumenta la puntuación NAS en 0,081 puntos (p=0,015). Sin embargo, la edad no resultó un buen predictor de la puntuación NAS (AbC=0,394; p=0,320). CONCLUSIÓN El cuidado de los adultos mayores en UCI se asocia con un aumento de la CTE en comparación con los adultos. El envejecimiento puede considerarse un factor asociado, pero no un buen predictor de la CTE en UCI.OBJETIVO Verificar se a idade é um preditor independente de Carga de trabalho de Enfermagem (CTE) em Unidade de Terapia Intensiva (UTI), de acordo com o grupo etário e qual sua capacidade preditiva como determinante de maior CTE em UTI. MÉTODO O estudo foi realizado entre 2012 e 2016. Amostra de conveniência composta por pacientes (idade ≥ 18) admitidos em nove UTI de um hospital universitário brasileiro. A idade foi considerada como variável independente e a CTE (mensurada pelo Nursing Activities Score ‒ NAS) como dependente. Os dados foram analisados por meio de análise de regressão linear e curva ROC. RESULTADOS 890 participantes (361 idosos), em sua maioria homens (58,1%). A média do NAS foi maior entre os idosos em comparação aos adultos (p=0,004), mas não entre os grupos etários (p=0,697). A idade foi responsável por 0,6% da pontuação do NAS. Para cada 1 ano de aumento da idade, a pontuação do NAS aumentou em 0,081 pontos (p=0,015). No entanto, a idade não foi um bom preditor de maior CTE (AUC = 0,394; p=0,320). CONCLUSÃO O cuidado de idosos em UTI está associado à maior CTE. A idade pode ser considerada um fator associado, mas não um bom preditor de CTE em UTI