Alzheimer’s disease (AD) is an age-related dementia, with the pathological hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as a contributing factor to the cognitive decline observed in AD. We hypothesized that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial respiration is impaired early in synaptic terminals, which are vital to cognitive performance, preferentially in cognitive centers of the brain. We compared oxygen consumption in synaptosomal and perikaryal mitochondria prepared from the cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice. Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in the cerebral cortex specifically in synaptosomal fraction, while the perikaryal mitochondria were unaffected. Neither mitochondrial fraction was affected in the cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic defect in synaptic terminals of mice overexpressing mutant beta-amyloid, in particular in an area of the brain important to cognition, points to an early role of mitochondrial defects in the onset of cognitive deficits in AD.
Purpose
Colonization of methicillin-resistant Staphylococcus aureus (MRSA) can be detected via nasal screens. Evidence indicates that negative MRSA nasal screens may be used to de-escalate anti-MRSA antibiotics in pulmonary infections. In the ICU, universal decolonization with intranasal mupirocin is implemented to reduce MRSA infection risk. This study aimed to determine whether mupirocin administration affects the reliability of MRSA PCR nasal screens.
Methods
This retrospective study divided subjects based on timing of intranasal mupirocin administration—before and after MRSA screen. Subjects with confirmed pulmonary infection that received vancomycin, blood/respiratory cultures, and had MRSA PCR screen collected were included. Subjects with concurrent infection requiring vancomycin or MRSA infection in prior 30 days were excluded. Primary outcome of this non-inferiority study was the negative predictive value (NPV) of the screen. Secondary outcomes included the positive predictive value (PPV), sensitivity, and specificity of the screen and duration of vancomycin.
Results
Ultimately, 125 subjects were included in each group. The NPV in the group receiving mupirocin before screen was 95.2%, whereas the NPV in the group receiving mupirocin after screen was 99%. The difference between groups was -3.8% (90% CI -7.8%-0.2%; p=0.31), which failed to meet non-inferiority criteria. The secondary outcomes of PPV, sensitivity and specificity of the screen were similar in both groups. The duration of vancomycin was significantly longer in subjects receiving mupirocin before screen (3 days vs. 2 days; p<0.05).
Conclusion
Intranasal mupirocin prior to the screen may reduce NPV in pulmonary infections. Approach de-escalation of vancomycin based on screen results with caution.
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