Demographic and infection characteristics of patients with carbapenem-resistant Enterobacteriaceae in a community hospital: Development of a bedside clinical score for risk assessment.

BACKGROUND: The objective of this study was to identify risk factors associated with the presence of carbapenem-resistant Enterobacteriaceae (CRE) infections to develop a clinical prediction model that can be used at patient bedside to identify subjects likely infected with a CRE pathogen. METHODS: This case-control study included patients aged ≥18 years admitted to Novant Health Forsyth Medical Center between January 1, 2012, and December 31, 2013, with CRE infections (cases) or non-CRE infections (controls). Controls were matched to their corresponding resistant case (3:1) based on pathogen, place of likely acquisition, isolate source, year of admission, and level of care. A risk prediction model was developed using variables independently associated with CRE isolation. Sensitivities and specificities were obtained at various point cutoffs, and a determination of the receiver operator characteristic (ROC) area under the curve (AUC) was performed. RESULTS: A total of 164 subjects were included. Independent risk factors for CRE included recent antibiotic therapy, recent immunosuppression, and Charlson Comorbidity Index score ≥4. Adjusted odds ratios were 13.37 (95% confidence interval [CI], 4.16-61.19), 6.69 (95% CI, 1.85-29.65), and 3.30 (95% CI, 1.34-8.40), respectively. Diagnostic performance of various score cutoffs for the model indicated a score ≥5 correlated with the highest accuracy (79%). The ROC AUC was 0.83. CONCLUSION: The risk prediction model displayed good discrimination and was an excellent predictor of CRE infection.

Respiratory plasticity after perinatal hyperoxia is not prevented by antioxidant supplementation.

Perinatal hyperoxia attenuates the hypoxic ventilatory response in rats by altering development of the carotid body and its chemoafferent neurons. In this study, we tested the hypothesis that hyperoxia elicits this plasticity through the increased production of reactive oxygen species (ROS). Rats were born and raised in 60% O(2) for the first two postnatal weeks while treated with one of two antioxidants: vitamin E (via milk from mothers whose diet was enriched with 1000 IU vitamin E kg(-1)) or a superoxide dismutase mimetic, manganese(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP; via daily intraperitoneal injection of 5-10 mg kg(-1)); rats were subsequently raised in room air until studied as adults. Peripheral chemoreflexes, assessed by carotid sinus nerve responses to cyanide, asphyxia, anoxia and isocapnic hypoxia (vitamin E experiments) or by hypoxic ventilatory responses (MnTMPyP experiments), were reduced after perinatal hyperoxia compared to those of normoxia-reared controls (all P<0.01); antioxidant treatment had no effect on these responses. Similarly, the carotid bodies of hyperoxia-reared rats were only one-third the volume of carotid bodies from normoxia-reared controls (P <0.001), regardless of antioxidant treatment. Protein carbonyl concentrations in the blood plasma, measured as an indicator of oxidative stress, were not increased in neonatal rats (2 and 8 days of age) exposed to 60% O(2) from birth. Collectively, these data do not support the hypothesis that perinatal hyperoxia impairs peripheral chemoreceptor development through ROS-mediated oxygen toxicity.

Respiratory plasticity in response to changes in oxygen supply and demand.

Aerobic organisms maintain O(2) homeostasis by responding to changes in O(2) supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O(2) supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O(2) capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O(2) supply and demand.