Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study.

QUESTION: Is broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders? METHODS: We performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events. RESULTS: 39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5-5.9; p<0.001) and IPTW analysis (OR 4.6, 95% CI 2.9-7.5; p<0.001). Broad-spectrum antibiotic use by either analysis was also associated with longer hospital stay, greater cost and increased CDI. Healthcare-associated pneumonia was not associated with mortality independent of broad-spectrum antibiotic use. In manual review we identified antibiotic-associated events in 17.5% of mortality cases. CONCLUSION: Broad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia.

Community-acquired pneumonia management and outcomes in the era of health information technology.

Pneumonia continues to be a leading cause of hospitalization and mortality. Implementation of health information technology (HIT) can lead to cost savings and improved care. In this review, we examine the literature on the use of HIT in the management of community-acquired pneumonia. We also discuss barriers to adoption of technology in managing pneumonia, the reliability and quality of electronic health data in pneumonia research, how technology has assisted pneumonia diagnosis and outcomes research. The goal of using HIT is to develop and deploy generalizable, real-time, computerized clinical decision support integrated into usual pneumonia care. A friendly user interface that does not disrupt efficiency and demonstrates improved clinical outcomes should result in widespread adoption.

Antibiotic Use and Outcomes After Implementation of the Drug Resistance in Pneumonia Score in ED Patients With Community-Onset Pneumonia.

BACKGROUND: To guide rational antibiotic selection in community-onset pneumonia, we previously derived and validated a novel prediction tool, the Drug-Resistance in Pneumonia (DRIP) score. In 2015, the DRIP score was integrated into an existing electronic pneumonia clinical decision support tool (ePNa). METHODS: We conducted a quasi-experimental, pre-post implementation study of ePNa with DRIP score (2015) vs ePNa with health-care-associated pneumonia (HCAP) logic (2012) in ED patients admitted with community-onset pneumonia to four US hospitals. Using generalized linear models, we used the difference-in-differences method to estimate the average treatment effect on the treated with respect to ePNa with DRIP score on broad-spectrum antibiotic use, mortality, hospital stay, and cost, adjusting for available patient-level confounders. RESULTS: We analyzed 2,169 adult admissions: 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015; inadequate initial empirical antibiotics were prescribed in 1.1% and 0.5%, respectively (P = .12). A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 and 33.0% in 2015 (P < .001). Vancomycin days of therapy per 1,000 patient days in 2012 were 287.3 compared with 238.8 in 2015 (P < .001). In the primary analysis, the average treatment effect among patients using the DRIP score was a reduction in broad-spectrum antibiotic use (OR, 0.62; 95% CI, 0.39-0.98; P = .039). However, the average effects for ePNa with DRIP on mortality, length of stay, and cost were not statistically significant. CONCLUSIONS: Electronic calculation of the DRIP score was more effective than HCAP criteria for guiding appropriate broad-spectrum antibiotic use in community-onset pneumonia.

Heparan sulfates mediate pressure-induced increase in lung endothelial hydraulic conductivity via nitric oxide/reactive oxygen species.

We investigated the nonlinear dynamics of the pressure vs. hydraulic conductivity (L(p)) relationship in lung microvascular endothelial cells and demonstrate that heparan sulfates, an important component of the endothelial glycocalyx, participate in pressure-sensitive mechanotransduction that results in barrier dysfunction. The pressure vs. L(p) relationship was complex, possessing both time- and pressure-dependent components. Pretreatment of lung capillary endothelial cells with heparanase III completely abolished the pressure-induced increase in L(p). This extends our (7) previous observation regarding heparan sulfates as mechanotransducers for shear stress. Inhibition of nitric oxide (NO) synthase with L-NAME (N(G)-nitro-L-arginine methyl ester HCl) and intracellular scavenging of reactive oxygen species (ROS) by TBAP [tetrakis-(4-benzoic acid) porphorin] significantly attenuated the pressure-induced L(p) response. Intracellular NO/ROS were visualized using the fluorescent dye, 2'7'-dichlorofluorescein diacetate (DCFA), and cells demonstrated a pressure-induced increase in intracellular fluorescence. Heparanase pretreatment significantly reduced the pressure-induced increase in intracellular fluorescence, suggesting that cell-surface heparan sulfates directly participate in mechanotransduction that results in NO/ROS production and increased permeability. This is the first report to demonstrate a role for heparan sulfates in pressure-mediated mechanotransduction and barrier regulation. These observations may have important clinical implications during conditions where pulmonary microvascular pressure is elevated.

Digital imaging system and virtual instrument platform for measuring hydraulic conductivity of vascular endothelial monolayers.

We have developed an automated, digital imaging system, controlled by two virtual instruments, to measure hydraulic conductivity (Lp) of cultured endothelial monolayers. Live digital images of multiple independent experiments were captured by custom-designed video processing software running in National Instruments LabVIEW 6.1. Fluid displacement data are automatically displayed in real time as both volumetric flux (Jv) and hydraulic conductivity (Lp). A separate data analysis program is used to display permeability values from stored displacement measurements and displays Jv or Lp of each monolayer. Optional statistical filters have been included to aid in data analysis. This new digital permeability system is able to measure flux rates over a dynamic range from 10(-9) cm/s/cm H2O to 10(-4) cm/s/cm H2O. Values obtained for cultured lung microvascular Lp are nearly identical to other cultured endothelial monolayers and also to values obtained in-vivo using the Landis-Michel technique and the split-drop method. The use of a commercially available platform allows the system configuration to be easily modified to suit the experimental needs. The technical development of this system is described in detail.