Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

A novel CPR-assist device vs. established chest compression techniques in infant CPR: A manikin study.

INTRODUCTION: Guidelines for infant CPR recommend the two-thumb encircling hands technique (TTT) and the two-finger technique (TFT) for chest compression. Some devices have been designed to assist with infant CPR, but are often not readily available. Syringe plungers may serve as an alternative infant CPR assist device given their availability in most hospitals. In this study, we aimed to determine whether CPR using a syringe plunger could improve CPR quality measurements on the Resusci-Baby manikin compared with traditional methods of infant CPR. METHODS: Compression area with a diameter of 1 to 2 cm is recommended in previous infant CPR device researches. In this is a randomized crossover manikin study, we examined the efficacy of the Syringe Plunger Technique (SPT) which uses the plunger of the 20 ml syringe with a 2 cm diameter flat piston, commonly available in hospital, for infant External Chest Compressions (ECC). Participants performed TTT, TFT and SPT ECC on Resusci® Baby QCPR® according to 2020 BLS guidelines. RESULTS: Sixty healthcare providers participated in this project. The median (IQR) ECC depths in the TTT, TFT and SPT in the first minute were 41 mm (40-42), 40 mm (38-41) and 40 mm (39-41), respectively, with p < 0.001. The median (IQR) ECC recoil in the TTT, TFT and SPT groups in the first minute was 15% (1-93), 64% (18-96) and 53% (8-95), respectively, with p = 0.003. The result in the second minute had similar findings. The SPT had the best QCPR score and less fatigue. CONCLUSION: The performance of chest compression depth and re-rebound ratio was statistically different among the three groups. TTT has good ECC depth and depth accuracy but poor recoil. TFT is the complete opposite. SPT can achieve a depth close to TTT and has a good recoil performance as TFT. Regarding comprehensive performance, SPT obtains the highest QCPR score, and SPT is also less fatigued. SPT may be an effective alternative technique for infant CPR.

Triage body temperature and its influence on patients with acute myocardial infarction.

BACKGROUND: Fever can occur after acute myocardial infarction (MI). The influence of body temperature (BT) after hospital arrival on patients with acute MI has rarely been investigated. METHODS: Patients who were diagnosed with acute MI in the emergency department (ED) of a tertiary teaching hospital between 1 January 2020 and 31 December 2020 were enrolled. Based on the tympanic temperature obtained at the ED triage, patients were categorized into normothermic (35.5°C-37.5°C), hypothermic (< 35.5°C), or hyperthermic (> 37.5°C) groups. The primary outcome was in-hospital cardiac arrest (IHCA), while the secondary outcomes were adverse events. Statistical significance was set at p < 0.05. RESULTS: There were 440 enrollees; significant differences were found among the normothermic (n = 369, 83.9%), hypothermic (n = 27, 6.1%), and hyperthermic (n = 44, 10.0%) groups in the triage respiratory rate (median [IQR]) (20.0 [4.0] cycles/min versus 20.0 [4.0] versus 20.0 [7.5], p = 0.009), triage heart rate (88.0 [29.0] beats/min versus 82.0 [28.0] versus 102.5 [30.5], p < 0.001), presence of ST-elevation MI (42.0% versus 66.7% versus 31.8%, p = 0.014), need for cardiac catheterization (87.3% versus 85.2% versus 72.7%, p = 0.034), initial troponin T level (165.9 [565.2] ng/L versus 49.1 [202.0] versus 318.8 [2002.0], p = 0.002), peak troponin T level (343.8 [1405.9] ng/L versus 218.7 [2318.2] versus 832.0 [2640.8], p = 0.003), length of ICU stay (2.0 [3.0] days versus 3.0 [8.0] versus 3.0 [9.5], p = 0.006), length of hospital stay (4.0 [4.5] days versus 6.0 [15.0] versus 10.5 [10.8], p < 0.001), and infection during hospitalization (19.8% versus 29.6% versus 63.6%, p < 0.001) but not in IHCA (7.6% versus 14.8% versus 11.4%, p = 0.323) or any adverse events (50.9% versus 48.1% versus 63.6%, p = 0.258). Multivariable analysis showed no significant association of triage BT with IHCA or any major complication. CONCLUSION: Triage BT did not show a significant association with IHCA or adverse events in patients with acute MI. However, triage BT could be associated with different clinical presentations and should warrant further investigation.

Biomechanical analysis of force distribution in one-handed and two-handed adult chest compression: a randomised crossover observational study.

INTRODUCTION: The standard method of chest compression for adults is a two-handed procedure. One-handed external chest compression (ECC) is used in some situations such as during transport of patients who had an out-of-hospital cardiac arrest, but the quality of one-handed ECC is still not well known. The distribution of force is related to the quality of chest compression and may affect the risk of injury. This study aimed to determine the differences in the quality and potential safety concern between one-handed ECC and two- handed ECC. METHODS: In this randomised crossover study, participants recruited from National Cheng Kung University Hospital and the ambulance team from the fire bureau were asked to perform one-handed and two-handed ECC on the Resusci Anne manikin according to standard 2015 ECC guidelines. The MatScan Pressure Measurement system was used to investigate the compression pressure and force distribution. RESULTS: Two-handed ECC had better results than one-handed ECC in terms of the median (IQR) depth (51.00 (41.50-54.75) mm vs 42.00 (27.00-49.00) mm, p=0.018), the proportion of depth accuracy (82.05% (13.95%-99.86%) vs 11.17% (0.00%-42.13%), p=0.028) and the proportion of incomplete recoil (0.23% (0.01%-0.44%) vs 2.42% (0.60%-4.21%), p=0.002). The maximum force (45.72 (36.10-80.84) kgf vs 35.64 (24.13-74.34) kgf, p<0.001) and ulnar-radial force difference (7.13 (-16.58 to 21.07) kgf vs 23.93 (11.19-38.74) kgf, p<0.001) showed statistically significant differences. The perceived fatigue of two-handed ECC versus one-handed ECC was 5.00 (3.00-6.00) vs 6.00 (5.00-8.00), p<0.001. CONCLUSION: The quality of one-handed ECC, based on depth and recoil, is worse than that of standard two-handed ECC. The pressure and force distribution of one-handed ECC result in greater ulnar pronation of the hand than that of two-handed ECC. One-handed ECC more easily causes operator fatigue. Acknowledging these findings and adjusting training for one-handed ECC would potentially improve the quality of cardiopulmonary resuscitation during transport.

Biomechanical analysis of force distribution in one-handed and two-handed child chest compression- a randomized crossover observational study.

BACKGROUND: Even force distribution would generate efficient external chest compression (ECC). Little research has been done to compare force distribution between one-hand (OH) and two-handed (TH) during child ECC. Therefore, this study was to investigate force distribution, rescuer perceived fatigue and discomfort/pain when applying OH and TH ECC in children. METHODS: Crossover manikin study. Thirty-five emergency department registered nurses performed lone rescuer ECC using TH and OH techniques, each for 2 min at a rate of at least 100 compressions/min. A Resusci Junior Basic manikin equipped with a MatScan pressure measurement system was used to collect data. The perceived exertion scale (modified Borg scale) and numerical rating scale (NRS) was applied to evaluate the fatigue and physical pain of delivering chest compressions. RESULTS: The maximum compression force (kg) delivered was 56.58 ± 13.67 for TH and 45.12 ± 7.90 for OH ECC (p <  0.001). The maximum-minimum force difference force delivered by TH and OH ECC was 52.24 ± 13.43 and 41.36 ± 7.57, respectively (p <  0.001). The mean caudal force delivered by TH and OH ECC was 29.45 ± 16.70 and 34.03 ± 12.01, respectively (p = 0.198). The mean cranial force delivered by TH and OH ECC was 27.13 ± 11.30 and 11.09 ± 9.72, respectively (p <  0.001). The caudal-cranial pressure difference delivered by TH and OH ECC was 19.14 ± 15.96 and 26.94 ± 14.48, respectively (p = 0.016). The perceived exertion and NRS for OH ECC was higher than that of the TH method (p < 0.001, p = 0.004, respectively). CONCLUSIONS: The TH method produced greater compression force, had more efficient compression, and delivered a more even force distribution, and produced less fatigue and physical pain in the rescuer than the OH method. TRIAL REGISTRATION: The Cheng Kung University Institutional Review Board A-ER-103-387. http://nckuhirb.med.ncku.edu.tw/sitemap.php.

Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects.

BACKGROUND: Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. RESULTS: Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1-2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. CONCLUSIONS: We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

How does the side of approach impact the force delivered during external chest compression?

BACKGROUND: We investigated the biomechanics of four external chest compression (ECC) approaches involving different sides of approach and hand placement during cardiopulmonary resuscitation (CPR). METHODS: A total of 60 participants (30 women and 30 men) with CPR certification performed standard continuous 2-min ECC on a Resusci Anne manikin with real-time feedback in four scenarios: rescuer at the manikin's right side with right hand chest contact (RsRc), rescuer at the manikin's right side with left hand chest contact (RsLc), rescuer at the manikin's left side with left hand chest contact (LsLc), and rescuer at the manikin's left side with right hand chest contact (LsRc). Pressure distribution maps of the palm, peak compression pressure, and compression forces were analysed. RESULTS: The participants' mean age, height, and weight was 24.8 ± 4.8 years, 165.8 ± 8.7 cm, and 62.7 ± 13.5 kg, respectively. Of the participants, 58 and 2 were right- and left-handed, respectively. Significant between-scenario differences were observed in ulnar-side palm pressure. Ulnar-radial pressure differences were higher in the LsLc and RsRc groups than in the LsRc and RsLc groups (0.69 ± 0.62 and 0.73 ± 050 kg/cm2 vs. 0.49 ± 0.49 and 0.50 ± 0.59 kg/cm2; respectively; p < 0.05). Ulnar-radial force differences were higher in the LsLc and RsRs groups than in the sLsLc and RsRs groups. CONCLUSIONS: The higher differences in pressure and force under the LsLc and RsRc approaches may lead to higher risks of potential injury. When performing standard-quality ECC, the LsRc and RsLc approaches, in which compression pressure and force are better distributed, may be more suitable than RsRc or LsLc.

Association of ABO Blood Type with Bleeding Severity in Patients with Acute Gastroesophageal Variceal Bleeding.

Background and Objectives: ABO blood types have been implicated as potential risk factors for various hemorrhagic diseases. No study has investigated the association between gastroesophageal variceal bleeding and ABO blood types. We aimed to evaluate the impact of ABO blood types on mortality and bleeding risk in acute gastroesophageal variceal bleeding. Materials and Methods: This is a retrospective observational study. Patients presenting with acute gastroesophageal varices bleeding diagnosed by endoscopy were enrolled, and were divided by blood type into a type O group and non-type O group. The outcomes were death within 30 days and the proportion of further bleeding. We used generalized linear mixed-effects models to analyze the outcomes. Results: A total of 327 patients and 648 records of emergency room visits were included. The 30-day mortality was 14.8% (21 of 142 patients) in the type O group, and 16.2% (30 of 185 patients) in the non-type O group (p = 0.532). Further bleeding within 30 days occurred in 34 cases (12.6%) in the type O group, and in 26 cases (6.9%) in the non-type O group (p = 0.539). Conclusions: There was no significant difference in blood transfusion volume in 24 h, recurrent bleeding rates, or mortality between patients with blood type O and those with non-type O.

Impact of climate change on disaster events in metropolitan cities -trend of disasters reported by Taiwan national medical response and preparedness system.

BACKGROUND: Taiwan is geographically located in a zone that is vulnerable to earthquakes, typhoons, floods, and landslide hazards and has experienced various disasters. Six Regional Emergency Medical Operation Centers (REMOCs) are integrated and administered by the Ministry of Health and Welfare (MOHW) to be responsible for emergency situations during disastrous events, such as the emission of chemical toxicants, traffic accidents, industrial materials containment, and typhoons. OBJECTIVE: To analyze events reported by the six REMOCs during the 2014 to 2018 for the government policy reference. METHODS: Data were collected from injured and death toll reports provided by local designated hospitals in the emergency medical reporting system. Disaster events were categorized into three categories: natural disaster (NDs), disasters associated with technology (DTs), and disasters associated with security/violence/others (DSVOs). The three categories were further subdivided into sub-categories. Variables considered for trend analyses included the number of wounded and deaths, event characteristics, date/time, and triage. The frequency of disaster events among the six REMOCs was compared using the chi-square test. We used the global information system (GIS) to describe the distribution of events in Taiwan metropolitan cities. The α-level was set at 0.05. RESULTS: Of 580 events during the study period, the distribution of disaster characteristics in the jurisdictions of the six REMOCs were different. The majority of disaster events were DTs (64.5%), followed by NDs (24.5%) and DSVOs (11.0%). Events for the three disaster categories in the six REMOCs were different (χ2-test, p < 0.001). Furthermore, for the Taipei branch (Northern Taiwan), other NDs, especially heatwaves and cold spells, were most reported in New Taipei City (92.2%) and showed an increasing annual trend; for the Kaohsiung branch (Southern Taiwan), DT events were the most reported, especially in Kaohsiung City; and for the Taichung branch (Central Taiwan), DSVOs were the most reported, especially in Taichung City. CONCLUSION: Our data revealed that extreme weather precautions reported in the Taipei branch were increasing. Disaster characteristics were different in each metropolitan city. Upgrading the ability to respond to natural disasters is ineluctable.

Differential effects of inappropriate empirical antibiotic therapy in adults with community-onset gram-positive and gram-negative aerobe bacteremia.

Bacteremia is associated with high morbidity and mortality, which contribute substantially to health care costs. A beneficial influence of appropriate empirical antimicrobial therapy (EAT) on patient outcome is evidenced; However, the evidence highlighting a comparison of clinical manifestations and of the effects of inappropriate EAT between Gram-positive and Gram-negative bacteremia is insufficient. In a retrospective 6-year cohort study, the total 2053 adults (Gram-positive, 566; Gram-negative 1487) presenting with community-onset monomicrobial aerobes bacteremia were recruited. Inappropriate EAT was defined as the first dose of an appropriate antimicrobial agent not being administered within the first 24 h after blood cultures were drawn. Although the bacteremia severity (a Pitt bacteremia score) at onset, comorbidity severity (the McCabe-Johnson classification), and 28-day mortality rate were similar in the two groups. Furthermore, after adjustment of independent predictors of 28-day mortality respectively recognized by the multivariate regression model in Gram-negative and Gram-positive groups, the Kaplan-Meier curve and Cox regression analysis revealed a significant difference (adjust odds ratio [AOR], 2.68; P < 0.001) between appropriate and inappropriate EAT in the Gram-negative group, but not in the Gram-positive group (AOR, 1.54; P = 0.06). Conclusively, patients with Gram-positive and Gram-negative bacteremia exhibited the similar presentation in bacteremia severity, but a greater impact of inappropriate EAT on survival of patients with Gram-negative aerobe bacteremia was evidenced.

Differential impacts of inappropriate empirical therapy on ED patients with Staphylococcus aureus and streptococci bacteremia.

BACKGROUND: Staphylococcus aureus (S. aureus) and streptococci are leading Gram-positive pathogens causing community-onset bacteremia. The comparisons of initial presentations and impacts of inappropriate empirical antimicrobial therapy (EAT) on clinical outcomes between the two pathogens are lacking. METHODS: In a 6-year cohort study, adult patients with community-onset monomicrobial S. aureus or streptococci bacteremia in the emergency department (ED) were studied. Clinical variables were collected retrospectively from medical records; the primary outcome was 4-week mortality after ED arrival. The Cox regression model was studied for effects of inappropriate EAT on 4-week mortality, after adjustment of independent predictors of 4-week mortality recognized by the multivariate regression model. RESULTS: A difference of clinical manifestations between S. aureus (291 patients) and streptococci (223) bacteremia was exhibited, in terms of bacteremia sources and comorbidity types, but bacteremia and comorbidity severity at ED arrival were similar. Furthermore, a longer period of the time-to-defervescence and hospitalization as well as more frequencies of septic metastasis were disclosed in S. aureus bacteremia, compared to streptococcal bacteremia. Of note, a significant impact (adjusted odds ratio [ORa], 2.23; 95% confidence interval [CI], 1.25-3.96) of inappropriate EAT on 4-week mortality was evidenced in S. aureus bacteremia, but not in streptococcal bacteremia (ORa, 2.88; 95% CI, 0.85-9.86). CONCLUSIONS: For adults having community-onset monomicrobial bacteremia, the similarity of bacteremia and comorbidity severity at ED arrivals were observed between causative microorganisms of S. aureus and streptococci, but a crucial impact of inappropriate EAT on short-term mortality was only observed in S. aureus.

Age-Related Trends in Adults with Community-Onset Bacteremia.

To understand the epidemiological variation in bacteremia characteristics among differently aged populations, adults with community-onset bacteremia during a 6-year period were studied in a retrospective cohort. A total of 2,349 bacteremic patients were stratified into four age categories: young adults (18 to 44 years old; 196 patients; 8.3%), adults (45 to 64 years old; 707 patients; 30.1%), the elderly (65 to 84 years old; 1,098 patients; 46.7%), and the oldest old (≥85 years old; 348 patients; 14.8%). Age-related trends in critical illness (a Pitt bacteremia score of ≥4) at bacteremia onset, antibiotic-resistant pathogens (extended-spectrum ß-lactamase [ESBL]-producing Escherichia coli, Klebsiella species, and Proteus mirabilis [EKP]; methicillin-resistant Staphylococcus aureus [MRSA]; and levofloxacin nonsusceptible EKP), inappropriate empirical antibiotic therapy (EAT), and 4-week mortality rate were observed. Using a multivariate regression model, critical illness at bacteremia onset (adjusted odds ratio [AOR], 9.03; P < 0.001) and inappropriate EAT (AOR, 2.67; P < 0.001) were the two leading predictors of 4-week mortality. Moreover, ESBL-producing EKP (AOR, 12.94; P < 0.001), MRSA (AOR, 8.66; P < 0.001), and levofloxacin-nonsusceptible EKP (AOR, 4.27; P < 0.001) were linked to inappropriate EAT. In conclusion, among adults with community onset bacteremia, significant positive age-related trends were noted in antibiotic-resistant pathogens and bacteremia severity, which were related to the increasing incidence of inappropriate EAT and 4-week mortality with age. Thus, different empirical antimicrobial regimens should be considered for distinct age groups.

Clinical Benefit of Appropriate Empirical Fluoroquinolone Therapy for Adults with Community-Onset Bacteremia in Comparison with Third-Generation-Cephalosporin Therapy.

Both fluoroquinolones (FQs) and third-generation cephalosporins (3rd-GCs) are commonly prescribed to treat bloodstream infections, but comparative efficacies between them were rarely studied. Demographics and clinical characteristics of 733 adults with polymicrobial or monomicrobial community-onset bacteremia empirically treated by an appropriate FQ (n = 87) or 3rd-GC (n = 646) were compared. A critical illness (respectively, 8.0% versus 19.0%; P = 0.01), an initial syndrome with severe sepsis (33.3% versus 50.3%; P = 0.003), or a fatal outcome at 28 days (4.6% versus 10.5%; P = 0.08) was less common in the FQ group. A total of 645 (88.0%) patients were febrile at initial presentation, and the FQ group with (FQ group versus 3rd-GC group, respectively, 7.6 days versus 12.0 days; P = 0.04) and without (3.8 days versus 5.4 days; P = 0.001) a critical illness had a shorter time to defervescence than the 3rd-GC group. By the propensity scores, 87 patients with appropriate FQ therapy were matched with 435 treated by 3rd-GC therapy at a ratio of 1:5, and there were no significant differences in terms of bacteremia severity, comorbidity severity, major comorbidities, causative microorganisms, and bacteremia sources between groups. Moreover, crude mortality rates at 28 days (FQ group versus 3rd-GC group, respectively, 4.6% versus 7.8%; P = 0.29) did not differ significantly. However, the time to defervescence was shorter in the FQ group (4.2 ± 3.6 versus 6.2 ± 7.6 days; P < 0.001). Conclusively in the adults with community-onset bacteremia, appropriate empirical FQ therapy was related to shorter time to defervescence than with 3rd-GC therapy, at least for those without a critical illness.

Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia.

BACKGROUND: Early administration of appropriate antimicrobials has been correlated with a better prognosis in patients with bacteremia, but the optimum timing of early antibiotic administration as one of the resuscitation strategies for severe bacterial infections remains unclear. METHODS: In a retrospective cohort study, adults with community-onset bacteremia at the emergency department (ED) were analyzed. Effects of different cutoffs of time to appropriate antibiotic (TtAa) administration after arrival at the ED on 28-day mortality were examined, after adjustment for independent predictors of mortality identified by multivariate regression analysis. RESULTS: Among 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96 hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54-0.65, all P < 0.001), after adjustment of the following prognostic factors: fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score (PBS) ≥4) on arrival at the ED, polymicrobial bacteremia, extended-spectrum beta-lactamase-producer bacteremia, underlying malignancies or liver cirrhosis, and bacteremia caused by pneumonia or urinary tract infections. The adverse impact of TtAa on 28-day mortality was most evident at the cutoff of 48 hours, as the lowest AOR was identified (0.54, P < 0.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48 hours in mildly ill (PBS = 0; AOR 0.47; P = 0.04) and moderately ill (PBS = 1-3; AOR 0.55; P = 0.02) patients, but shifted to 1 hour in critically ill patients (PBS ≥4; AOR 0.56; P < 0.001). CONCLUSIONS: The time from triage to administration of appropriate antimicrobials is one of the primary determinants of mortality. The optimum timing of appropriate antimicrobial administration is the first 48 hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1 hour after critically ill patients arrive at the ED.

Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation.

IFN-γ mediates chemically induced skin inflammation; however, the mechanism by which IFN-γ-producing cells are recruited to the sites of inflammation remains undefined. Secretion of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, from damaged cells may promote immune cell recruitment. We hypothesized that MIF triggers an initial step in the chemotaxis of IFN-γ-producing cells in chemically induced skin inflammation. Using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears, MIF expression was examined, and its role in this process was investigated pharmacologically. The cell populations targeted by MIF, their receptor expression patterns, and the effects of MIF on cell migration were examined. TPA directly caused cytotoxicity accompanied by MIF release in mouse ear epidermal keratinocytes, as well as in human keratinocytic HaCaT cells. Treatment with the MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester considerably attenuated TPA-induced ear swelling, leukocyte infiltration, epidermal cell proliferation, and dermal angiogenesis. Inhibition of MIF greatly diminished the dermal infiltration of IFN-γ(+) NKT cells, whereas the addition of exogenous TPA and MIF to NKT cells promoted their IFN-γ production and migration, respectively. MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation. In TPA-induced skin inflammation, MIF is released from damaged keratinocytes and then triggers the chemotaxis of CD74(+)CXCR2(+) NKT cells for IFN-γ production.

Clinical features and impact of empirical therapy in cirrhotic adults with community-onset bacteremia.

OBJECTIVES: The objectives were to investigate the clinical characteristics of community-onset bacteremia in cirrhotic adults visiting the emergency department (ED), as well as the clinical impact of empirical antibiotics on their outcome. METHODS: Cirrhotic adults with community-onset bacteremia who visited the ED from January 2005 to December 2009 were included retrospectively. Clinical data and outcome were collected from the medical chart. The in vitro susceptibility was measured by the broth microdilution method. RESULTS: Of the 246 bacteremic episodes in cirrhotic patients, the major sources of bacteremia included intraabdominal infections (111, 45.1%), primary bacteremia (43, 17.5%), urinary tract infection (39, 15.9%), and soft tissue infection (22, 8.9%). Of the 258 bacteremic pathogens identified, Escherichia coli (83 isolates, 33.7%) and Klebsiella pneumoniae (61, 23.6%) were the most common microorganisms. In the multivariate analysis, delayed appropriate antibiotic therapy (>72 hours; odds ratio [OR], 4.29; P=.003), serum creatinine greater than 1.5 mg/dL at the ED (OR, 3.12; P=.005), severe sepsis (OR, 3.61; P=.01), Pittsburgh bacteremia score of at least 4 (OR, 2.66; P=.04), bacteremia due to pneumonia (OR, 5.44; P=.02), and a comorbidity of diabetes mellitus (OR, 3.54; P=.004) were independently associated with the 28-day mortality. CONCLUSIONS: Focusing on cirrhotic adults with community-onset bacteremia, we emphasized that the cirrhosis severity is one of the critical factors when choosing empirical antimicrobial therapy and that the strategy of empirical therapy is warranted for cirrhotic adults with severe decompensation (Child's C group). For critically ill patients, especially in those with Child's C group, only piperacillin/tazobactam, ertapenem, or imipenem treatment was warranted because of susceptibility rate of greater than 90%.