Outcome of Immediate Versus Early Antibiotics in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: Debate exists about the mortality benefit of administering antibiotics within either 1 or 3 hours of sepsis onset. We performed this meta-analysis to analyze the effect of immediate (0 to 1 hour after onset) versus early (1 to 3 hours after onset) antibiotics on mortality in patients with severe sepsis or septic shock. METHODS: This review was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searched databases included PubMed, EMBASE, Web of Science, and Cochrane Library, as well as gray literature. Included studies were conducted with consecutive adults with severe sepsis or septic shock who received antibiotics within each period and provided mortality data. Data were extracted by 2 independent reviewers and pooled with random effects. Two authors independently assessed quality of evidence across all studies with Cochrane's Grading of Recommendations Assessment, Development and Evaluation methodology and risk of bias within each study, using the Newcastle-Ottawa Scale. RESULTS: Thirteen studies were included: 5 prospective longitudinal and 8 retrospective cohort ones. Three studies (23%) had a high risk of bias (Newcastle-Ottawa Scale). Overall, quality of evidence across all studies (Grading of Recommendations Assessment, Development and Evaluation) was low. Pooling of data (33,863 subjects) showed no difference in mortality between patients receiving antibiotics in immediate versus early periods (odds ratio 1.09; 95% confidence interval 0.98 to 1.21). Analysis of severe sepsis studies (8,595 subjects) found higher mortality in immediate versus early periods (odds ratio 1.29; 95% confidence interval 1.09 to 1.53). CONCLUSION: We found no difference in mortality between immediate and early antibiotics across all patients. Although the quality of evidence across studies was low, these findings do not support a mortality benefit for immediate compared with early antibiotics across all patients with sepsis.

Violet 405-nm light: a novel therapeutic agent against common pathogenic bacteria.

BACKGROUND: The increasing incidence of healthcare-associated infections (HAIs) and multidrug-resistant organisms demonstrate the need for innovative technological solutions. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, and Pseudomonas aeruginosa in particular are common pathogens responsible for a large percentage of indwelling medical device-associated clinical infections. The bactericidal effects of visible light sterilization (VLS) using 405-nm is one potential therapeutic under investigation. MATERIALS AND METHODS: Light-emitting diodes of 405-nm were used to treat varying concentrations of S aureus, S pneumonia, E coli, and P aeruginosa. Irradiance levels between 2.71 ± 0.20 to 9.27 ± 0.36 mW/cm2 and radiant exposure levels up to 132.98 ± 6.68 J/cm2 were assessed. RESULTS: Dose-dependent effects were observed in all species. Statistically significant reductions were seen in both Gram-positive and Gram-negative bacteria. At the highest radiant exposure levels, bacterial log10 reductions were E coli-6.27 ± 0.54, S aureus-6.10 ± 0.60, P aeruginosa-5.20 ± 0.84, and S pneumoniae-6.01 ± 0.59. Statistically significant results (<0.001*) were found at each time point. CONCLUSIONS: We have successfully demonstrated high-efficacy bacterial reduction using 405-nm light sterilization. The VLS showed statistical significance against both Gram-positive and Gram-negative species with the given treatment times. The ß-lactam antibiotic-resistant E coli was the most sensitive to VLS, suggesting light therapy could a suitable option for sterilization in drug-resistant bacterial species. This research illustrates the potential of using VLS in treating clinically relevant bacterial infections.

Violet 405 nm light: A novel therapeutic agent against ß-lactam-resistant Escherichia coli.

BACKGROUND AND OBJECTIVE: Approximately 1.7 million patients are affected by hospital-acquired infections every year in the United States. The increasing prevalence of multidrug-resistant bacteria associated with these infections prompts the investigation of alternative sterilization and antibacterial therapies. One method currently under investigation is the antibacterial properties of visible light. This study examines the effect of a visible light therapy (VLT) on ß-lactam-resistant Escherichia coli, a common non-skin flora pathogen responsible for a large percentage of indwelling medical device-associated clinical infection. MATERIALS AND METHODS: 405 nm light-emitting diodes were used to treat varying concentrations of a common laboratory E. coli K-12 strain transformed with the pCIG mammalian expression vector. This conferred ampicillin resistance via expression of the ß-lactamase gene. Bacteria were grown on sterile polystyrene Petri dishes plated with Luria-Bertani broth. Images of bacterial growth colonies on plates were processed and analyzed using ImageJ. Irradiance levels between 2.89 ± 0.19 and 9.45 ± 0.63 mW cm(-2) and radiant exposure levels between 5.60 ± 0.39 and 136.91 ± 4.06 J cm(-2) were tested. RESULTS: VLT with variable irradiance and constant treatment time (120 minutes) demonstrated significant reduction (P < 0.001) in E. coli between an irradiance of 2.89 mW cm(-2) (81.70%) and 9.37 mW cm(-2) (100.00%). Similar results were found with variable treatment time with constant irradiance. Log10 reduction analysis produced between 1.98 ± 0.53 (60 minute treatment) and 6.27 ± 0.54 (250 minute treatment) log10 reduction in bacterial concentration (P < 0.001). CONCLUSIONS: We have successfully demonstrated a significant bacterial reduction using high intensity 405 nm light. Illustrating the efficacy of this technology against a ß-lactam-resistant E. coli is especially relevant to the need for novel methods of sterilization in healthcare settings. These results suggest that VLT using 405 nm light could be a suitable clinical option for eradication of ß-lactam-resistant E. coli. Visible light kills statistically significant concentrations of E. coli. Antibiotic-resistant Gram-negative bacteria exhibits sensitivity to 405 nm light. Greater than 6 log10 reduction in ß-lactam-resistant E. coli when treated with visible light therapy.

The utility of transcutaneous carbon dioxide measurements in the emergency department: A prospective cohort study.

BACKGROUND: Rapid identification of patients with occult injury and illness in the emergency department can be difficult. Transcutaneous carbon dioxide (TCO2) and oxygen (TO2) measurements may be non-invasive surrogate markers for the identification of such patients. OBJECTIVES: To determine if TCO2 or TO2 are useful adjuncts for identifying severe illness and the correlation between TCO2, lactate, and end tidal carbon dioxide (ETCO2). METHODS: Prospective TCO2 and TO2 measurements at a tertiary level 1 trauma center were obtained using a transcutaneous sensor on 300 adult patients. Severe illness was defined as death, intensive care unit (ICU) admission, bilevel positive airway pressure, vasopressor use, or length of stay >2 days. TCO2 and TO2 were compared to illness severity using t tests and correlation coefficients. RESULTS: Mean TO2 did not differ between severe illness (58.9, 95% CI 54.9-62.9) and non-severe illness (58.0, 95% CI 54.7-61.1). Mean TCO2 was similar between severe (34.6, 95% CI 33-36.2) vs non-severe illness (35.9, 95% CI 34.7-37.1). TCO2 was 28.7 (95% CI 24.0-33.4) for ICU vs. 35.9 (95% CI 34.9-36.9) for non-ICU patients. The mean TCO2 in those with lactate > 2.0 was 29.8 (95% CI 25.8-33.8) compared with 35.7 (95% CI 34.9-36.9) for lactate < 2.0. TCO2 was not correlated with ETCO2 (r = 0.32, 95% CI 0.22-0.42). CONCLUSION: TCO2 could be a useful adjunct for identifying significant injury and illness and patient outcomes in an emergency department (ED) population. TO2 did not predict severe illness. TCO2 and ETCO2 are only moderately correlated, indicating that they are not equivalent and may be useful under different circumstances.

Effect of Heliox on Respiratory Outcomes during Rigid Bronchoscopy in Term Lambs.

Objective To (1) compare physiologic changes during rigid bronchoscopy during spontaneous and mechanical ventilation and (2) evaluate the efficacy of a helium-oxygen (heliox) gas mixture as compared with room air during rigid bronchoscopy. Study Design Crossover animal study evaluating physiologic parameters during rigid bronchoscopy. Outcomes were compared with predicted computational fluid analysis. Setting Simulated ventilation via computational fluid dynamics analysis and term lambs undergoing rigid bronchoscopy. Methods Respiratory and physiologic outcomes were analyzed in a lamb model simulating bronchoscopy during foreign body aspiration to compare heliox with room air. The main outcome measures were blood oxygen saturation, heart rate, blood pressure, partial pressure of oxygen, and partial pressure of carbon dioxide. Computational fluid dynamics analysis was performed with SOLIDWORKS within a rigid pediatric bronchoscope during simulated ventilation comparing heliox with room air. Results For room air, lambs desaturated within 3 minutes during mechanical ventilation versus normal oxygen saturation during spontaneous ventilation ( P = .01). No improvement in respiratory outcomes was seen between heliox and room air during mechanical ventilation. Computational fluid dynamics analysis demonstrates increased turbulence within size 3.5 bronchoscopes when comparing heliox and room air. Meaningful comparisons could not be made due to the intolerance of the lambs to heliox in vivo. Conclusion During mechanical ventilation on room air, lambs desaturate more quickly during rigid bronchoscopy on settings that should be adequate. Heliox does not improve ventilation during rigid bronchoscopy.

Flow dynamics in pediatric rigid bronchoscopes using computer-aided design modeling software.

OBJECTIVES/HYPOTHESIS: Observed complications during rigid bronchoscopy, including hypercarbia and hypoxemia, prompted us to assess how well rigid bronchoscopes serve as an airway device. We performed computer-aided design flow analysis of pediatric rigid bronchoscopes to gain insight into flow dynamics. STUDY DESIGN: We made accurate three-dimensional computer models of pediatric rigid bronchoscopes and endotracheal tubes. SOLIDWORKS (Dassault Systemes, Vélizy-Villacoublay, France) flow analysis software was used to analyze fluid dynamics during pressure-controlled and volume-controlled ventilation. METHODS: Flow analysis was performed on rigid bronchoscopes and similar outer diameter endotracheal tubes comparing resistance, flow, and turbulence during two ventilation modalities and in common surgical scenarios. RESULTS: Increased turbulent flow was observed in bronchoscopes compared to more laminar flow in endotracheal tubes of similar outer diameter. Flow analysis displayed higher resistances in all pediatric bronchoscope sizes except one (3.0 bronchoscope) compared to similar-sized endotracheal tubes. Loss of adequate ventilation was observed if the bronchoscope was not assembled correctly or if increased peak inspiratory pressures were needed. Anesthesia flow to the patient was reduced by 63% during telescope insertion. CONCLUSIONS: Flow analysis illustrates increased turbulent flow and increased airflow resistance in all but one size of pediatric bronchoscopes compared to endotracheal tubes. This increased turbulence and resistance, along with the unanticipated gas distal exit pattern, may contribute to the documented hypercarbia and hypoxemia during procedures. These findings may explain why hypoxemia and hypercarbia are commonly observed during rigid bronchoscopy, especially when positive pressure ventilation is needed. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1940-1945, 2016.