Active Monitoring and Feedback to Improve Blood Culture Fill Volumes and Positivity Across a Large Integrated Health System.

BACKGROUND: The sensitivity of blood cultures increases with the volume of blood collected. However, hospitals face challenges in collecting adequate volume, and underfilled blood bottles are ubiquitous. METHODS: Blood bottle fill volumes were measured using an automated monitoring system across multiples sites (10 hospitals, 3 laboratories) within a large suburban/urban health system. Baseline fill volumes were measured for 4 months. A quality improvement program was then implemented over 36 months. Strategies to improve fill volumes included education, standardized data collection, novel and unblinded information cascades, targeted communication, and bottle markings for blood collectors. RESULTS: A total of 516 201 blood cultures were evaluated over 40 months. In the preimplementation period (January-April 2015), no hospitals collected the recommended 8-10 mL/bottle, and the average system fill volume was 2.3 mL. In the final postimplementation period (January-April 2018), 7 of 10 hospitals achieved ≥8 mL per bottle and the system average increased to 8.6 mL (P < .0001). The positivity rate increased 20%, from 7.39% to 8.85% (P < .001), whereas the contamination rate did not change and remained low. Compared to the preimplementation period, the odds of positive cultures containing potential pathogens increased to 1.18 (95% confidence interval, 1.05-1.32; P = .003). CONCLUSIONS: Here we show that underfilled blood cultures are extremely common but that operational and educational strategies can result in sustained improvements across a complex network of hospitals and laboratories. This leads to increased detection of pathogens, which can have tremendous impact on the management of bloodstream infections and sepsis.

Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells.

Exposure of animals to hyperoxia results in respiratory failure and death within 72 h. Histologic evaluation of the lungs of these animals demonstrates epithelial apoptosis and necrosis. Although the generation of reactive oxygen species (ROS) is widely thought to be responsible for the cell death observed following exposure to hyperoxia, it is not clear whether they act upstream of activation of the cell death pathway or whether they are generated as a result of mitochondrial membrane permeabilization and caspase activation. We hypothesized that the generation of ROS was required for hyperoxia-induced cell death upstream of Bax activation. In primary rat alveolar epithelial cells, we found that exposure to hyperoxia resulted in the generation of ROS that was completely prevented by the administration of the combined superoxide dismutase/catalase mimetic EUK-134 (Eukarion, Inc., Bedford, MA). Exposure to hyperoxia resulted in the activation of Bax at the mitochondrial membrane, cytochrome c release, and cell death. The administration of EUK-134 prevented Bax activation, cytochrome c release, and cell death. In a mouse lung epithelial cell line (MLE-12), the overexpression of Bcl-XL protected cells against hyperoxia by preventing the activation of Bax at the mitochondrial membrane. We conclude that exposure to hyperoxia results in Bax activation at the mitochondrial membrane and subsequent cytochrome c release. Bax activation at the mitochondrial membrane requires the generation of ROS and can be prevented by the overexpression of Bcl-XL.

Hyperoxia-induced apoptosis does not require mitochondrial reactive oxygen species and is regulated by Bcl-2 proteins.

Exposure of animals to hyperoxia results in lung injury that is characterized by apoptosis and necrosis of the alveolar epithelium and endothelium. The mechanism by which hyperoxia results in cell death, however, remains unclear. We sought to test the hypothesis that exposure to hyperoxia causes mitochondria-dependent apoptosis that requires the generation of reactive oxygen species from mitochondrial electron transport. Rat1a cells exposed to hyperoxia underwent apoptosis characterized by the release of cytochrome c, activation of caspase-9, and nuclear fragmentation that was prevented by the overexpression of Bcl-X(L.) Murine embryonic fibroblasts from bax(-/-) bak(-/-) mice were resistant to hyperoxia-induced cell death. The administration of the antioxidants manganese (III) tetrakis (4-benzoic acid) porphyrin, ebselen, and N-acetylcysteine failed to prevent cell death following exposure to hyperoxia. Human fibrosarcoma cells (HT1080) lacking mitochondrial DNA (rho(0) cells) that failed to generate reactive oxygen species during exposure to hyperoxia were not protected against cell death following exposure to hyperoxia. We conclude that exposure to hyperoxia results in apoptosis that requires Bax or Bak and can be prevented by the overexpression of Bcl-X(L). The mitochondrial generation of reactive oxygen species is not required for cell death following exposure to hyperoxia.