Respiratory Virus-Specific Nasopharyngeal Lipidome Signatures and Severity in Infants With Bronchiolitis: A Prospective Multicenter Study.

BACKGROUND: In infant bronchiolitis, recent evidence indicates that respiratory viruses (eg, respiratory syncytial virus [RSV], rhinovirus [RV]) contribute to the heterogeneity of disease severity. Of the potential pathobiological molecules, lipids serve as signaling molecules in airway inflammation. However, little is known about the role of the airway lipidome in between-virus heterogeneity and disease severity. METHODS: In this multicenter prospective study of 800 infants hospitalized for RSV or RV bronchiolitis, we analyzed nasopharyngeal lipidome data. We examined discriminatory lipids between RSV and RV infection and the association of the discriminatory lipids with bronchiolitis severity, defined by positive pressure ventilation (PPV) use. RESULTS: We identified 30 discriminatory nasopharyngeal lipid species and 8 fatty acids between RSV and RV infection. In the multivariable models adjusting for patient-level confounders, 8 lipid species-for example, phosphatidylcholine (18:2/18:2) (adjusted odds ratio [aOR], 0.23 [95% confidence interval {CI}, .11-.44]; false discovery rate [FDR] = 0.0004) and dihydroceramide (16:0) (aOR, 2.17 [95% CI, 1.12-3.96]; FDR = 0.04)-were significantly associated with the risk of PPV use. Additionally, 6 fatty acids-for example, eicosapentaenoic acid (aOR, 0.27 [95% CI, .11-.57]; FDR = 0.01)-were also significantly associated with the risk of PPV use. CONCLUSIONS: In infants hospitalized for bronchiolitis, the nasopharyngeal lipidome plays an important role in the pathophysiology of between-virus heterogeneity and disease severity.

Characteristics of the pulmonary opacities on chest CT associated with difficulty in short-term liberation from veno-venous ECMO in patients with severe ARDS.

BACKGROUND: It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (< 14 days). METHODS: This multicenter retrospective study was conducted in adult patients initiated on V-V ECMO for severe ARDS between January 2014 and June 2022. The pulmonary opacities on CT at the time of initiation of the ECMO support were evaluated in a blinded manner, focusing on the following three characteristics of the opacities: (1) their distribution (focal/diffuse on the dorso-ventral axis or unilateral/bilateral on the left-right axis); (2) their intensity (pure ground glass/pure consolidation/mixed pattern); and (3) the degree of fibroproliferation (signs of traction bronchiectasis or reticular opacities). RESULTS: Among the 153 patients, 72 (47%) were successfully liberated from ECMO in the short term, while short-term liberation failed in the remaining 81 (53%) patients. Multivariate logistic regression analysis showed that the presence of mixed-pattern pulmonary opacities and signs of traction bronchiectasis, but not the distribution of the opacities, were independently associated with difficulty in short-term liberation (OR [95% CI]; 4.8 [1.4-16.5] and 3.9 [1.4-11.2], respectively). CONCLUSIONS: The presence of a mixed pattern of the pulmonary opacities and signs of traction bronchiectasis on the chest CT were independently associated with difficulty in short-term liberation from V-V ECMO in severe ARDS patients.

Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome.

BACKGROUND: The lung microbiome maintains the homeostasis of the immune system within the lungs. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; however, the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients. METHODS: We analyzed the lung microbiome from the bronchoalveolar lavage fluid (BALF) of patients with ARDS and control subjects. We measured the copy numbers of 16S rRNA and the serum and BALF cytokines (interleukin [IL]-6, IL-8, receptor for advanced glycation end products, and angiopoietin-2). RESULTS: We analyzed 47 mechanically ventilated patients diagnosed with (n = 40) or without (n = 7; control) ARDS. The alpha diversity was significantly decreased in ARDS patients compared with that of the controls (6.24 vs. 8.07, P = 0.03). The 16S rRNA gene copy numbers tended to be increased in the ARDS group compared with the controls (3.83 × 106 vs. 1.01 × 105 copies/mL, P = 0.06). ARDS patients were subdivided into the hospital survivor (n = 24) and non-survivor groups (n = 16). Serum IL-6 levels were significantly higher in the non-survivors than in the survivors (567 vs. 214 pg/mL, P = 0.027). The 16S rRNA copy number was significantly correlated with serum IL-6 levels in non-survivors (r = 0.615, P < 0.05). The copy numbers and relative abundance of betaproteobacteria were significantly lower in the non-survivors than in the survivors (713 vs. 7812, P = 0.012; 1.22% vs. 0.08%, P = 0.02, respectively). Conversely, the copy numbers of Staphylococcus, Streptococcus and Enterobacteriaceae were significantly correlated with serum IL-6 levels in the non-survivors (r = 0.579, P < 0.05; r = 0.604, P < 0.05; r = 0.588, P < 0.05, respectively). CONCLUSIONS: The lung bacterial burden tended to be increased, and the alpha diversity was significantly decreased in ARDS patients. The decreased Betaproteobacteria and increased Staphylococcus, Streptococcus and Enterobacteriaceae might represent a unique microbial community structure correlated with increased serum IL-6 and hospital mortality. TRIAL REGISTRATION: The institutional review boards of Hiroshima University (Trial registration: E-447-4, registered 16 October 2019) and Kyoto Prefectural University of Medicine (Trial registration: ERB-C-973, registered 19 October 2017) approved an opt-out method of informed consent.

Rapid-onset plasma leakage of extracorporeal oxygenation membranes possibly due to hyperbilirubinemia.

Extracorporeal membrane oxygenation (ECMO) is an emerging tool for supporting cardiopulmonary function in patients with cardiorespiratory failure or arrest. The oxygenator of the ECMO circuit requires effective oxygenation and removal of carbon dioxide from the blood. Major problems that can occur with the oxygenator include plasma leakage, one of the late-onset serious complications necessitating device replacement. However, the rapid onset of plasma leakage is rare. We present a 1-year-old boy with acute respiratory failure due to Pneumocystis and Aspergillus pneumonia. He presented with tachypnea, tachycardia, and hypoxemia despite the ventilatory support, and was therefore placed on venoarterial ECMO with a drainage catheter from the right internal jugular vein (12 Fr) and a return catheter to the right internal carotid artery (10 Fr). Extracorporeal circulation was initiated at a blood flow of 1 L/min (145 mL/kg/min) and a sweep gas flow of 1 L/min with FiO2 of 0.7. Although he was successfully weaned from the venoarterial ECMO on day 15 with an improvement of cardiopulmonary function, he was later placed on venoarterial ECMO again because of the progression of pulmonary hypertension. Laboratory tests showed increased concentrations of hepatic enzymes and hyperbilirubinemia (total bilirubin 31.6 mg/dL). Six hours after starting ECMO circulation, plasma leakage from the oxygenator occurred. Although we replaced the oxygenator with a new one, the replacement showed plasma leakage after 6 h. Disassembly of the oxygenator revealed congestion from bilirubin in the membrane fibers. We described a case of repeated, rapid-onset plasma leakage after implementation of ECMO. Hyperbilirubinemia was likely associated with the plasma leakage of this patient.

Pediatric cardiorespiratory failure successfully managed with venoarterial-venous extracorporeal membrane oxygenation: a case report.

BACKGROUND: Venoarterial-venous extracorporeal membrane oxygenation (VAV ECMO) configuration is a combined procedure of extracorporeal membrane oxygenation (ECMO). The proportion of cardiac and respiratory support can be controlled by adjusting arterial and venous return. Therefore, VAV ECMO can be applicable as a bridging therapy in the transition from venoarterial (VA) to venovenous (VV) ECMO. CASE PRESENTATION: We present an 11-year-old girl with chemotherapy-induced myocarditis requiring extracorporeal cardiorespiratory support. She showed progressive hypotension, tachycardia, hyperlactemia, and tachypnea under support of catecholamines. Echocardiography showed severe left ventricular hypokinesis with an ejection fraction of 30 %. She was placed on VA ECMO with a drainage catheter from the right femoral vein (19.5 Fr) and a return catheter to the right femoral artery (16.5 Fr). Extracorporeal circulation was initiated at a blood flow of 2.0 L/min (59 mL/kg/min). On day 31, although cardiac function had improved, persistent pulmonary failure made weaning from VA ECMO difficult. We planned transition from VA ECMO to VAV ECMO to ensure gradual tapering of extracorporeal cardiac support while evaluating cardiopulmonary function. An additional return cannula (13.5 Fr) was inserted from the right internal jugular vein, which was connected to the circuit branch from the original returning cannula. We then gradually shifted the blood from the femoral artery to the right internal jugular vein over 24 h. She was successfully switched from VA to VV ECMO via VAV ECMO. CONCLUSIONS: VAV ECMO might be an option in ensuring oxygenation to the coronary circulation and allowing time to adequately evaluate cardiac function during transition from VA to VV ECMO. Further investigations using larger cohorts are necessary to validate the efficacy of VAV ECMO as a bridging therapy in the transition from VA to VV ECMO.

External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study.

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82-0.93) and 0.83 (0.76-0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83-0.96) and 0.67 (0.55-0.79) for the low, 0.63 (0.54-0.74) and 0.67 (0.55-0.79) for the moderate, and 0.27 (0.17-0.37) and 1.00 (1.00-1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.

Temperature management using an intervascular cooling device for a COVID-19 patient with refractory hyperthermia.

COVID-19 is a life-threatening disease complicated by hyperinflammation followed by multi-organ failure. Although refractory hyperthermia in COVID-19 contributes to an unfavorable prognosis, little is known about effective interventions. We present a case of successful temperature management using an intravascular cooling device in a patient with COVID-19 who developed refractory hyperthermia.

Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity risk.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics. METHODS: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data. RESULTS: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungiM.restrictavirusRSV/RV, B) fungiM.restrictavirusRSV, C) fungiM.globosavirusRSV/RV, D) funginot-detectedvirusRSV/RV mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05). INTERPRETATION: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics. FUNDING: This study was supported by the National Institutes of Health.

Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study.

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography−tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06−0.76), glycine (adjOR 0.25, 95%CI 0.07−0.85), and glutamate (adjOR 0.25, 95%CI 0.07−0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82−0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

Proteins produced by Streptococcus species in the lower respiratory tract can modify antiviral responses against influenza virus in respiratory epithelial cells.

Seasonal influenza spreads during winter in temperate countries. Primary viral pneumoniae resulting from aggravation triggers acute respiratory distress syndrome, which is a serious respiratory disorder. We have identified a unique pattern of lung microbiota in patients with the syndrome. In this study, we hypothesized that the unique microbiota was also associated with primary influenza viral pneumoniae. Bacterial culture supernatants of Streptococcus oralis and Streptococcus mitis detected from the patients significantly increased viral replication (maximum 10-fold increase) in lung epithelial cells. Our results suggest that the lung environment microbiota is significantly involved in viral replication.

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome.

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM.

Patient-ventilator asynchrony, impact on clinical outcomes and effectiveness of interventions: a systematic review and meta-analysis.

BACKGROUND: Patient-ventilator asynchrony (PVA) is a common problem in patients undergoing invasive mechanical ventilation (MV) in the intensive care unit (ICU), and may accelerate lung injury and diaphragm mis-contraction. The impact of PVA on clinical outcomes has not been systematically evaluated. Effective interventions (except for closed-loop ventilation) for reducing PVA are not well established. METHODS: We performed a systematic review and meta-analysis to investigate the impact of PVA on clinical outcomes in patients undergoing MV (Part A) and the effectiveness of interventions for patients undergoing MV except for closed-loop ventilation (Part B). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ClinicalTrials.gov, and WHO-ICTRP until August 2020. In Part A, we defined asynchrony index (AI) ≥ 10 or ineffective triggering index (ITI) ≥ 10 as high PVA. We compared patients having high PVA with those having low PVA. RESULTS: Eight studies in Part A and eight trials in Part B fulfilled the eligibility criteria. In Part A, five studies were related to the AI and three studies were related to the ITI. High PVA may be associated with longer duration of mechanical ventilation (mean difference, 5.16 days; 95% confidence interval [CI], 2.38 to 7.94; n = 8; certainty of evidence [CoE], low), higher ICU mortality (odds ratio [OR], 2.73; 95% CI 1.76 to 4.24; n = 6; CoE, low), and higher hospital mortality (OR, 1.94; 95% CI 1.14 to 3.30; n = 5; CoE, low). In Part B, interventions involving MV mode, tidal volume, and pressure-support level were associated with reduced PVA. Sedation protocol, sedation depth, and sedation with dexmedetomidine rather than propofol were also associated with reduced PVA. CONCLUSIONS: PVA may be associated with longer MV duration, higher ICU mortality, and higher hospital mortality. Physicians may consider monitoring PVA and adjusting ventilator settings and sedatives to reduce PVA. Further studies with adjustment for confounding factors are warranted to determine the impact of PVA on clinical outcomes. Trial registration protocols.io (URL: https://www.protocols.io/view/the-impact-of-patient-ventilator-asynchrony-in-adu-bsqtndwn , 08/27/2020).

Rhythm-control therapy for new-onset atrial fibrillation in critically ill patients: A post hoc analysis from the prospective multicenter observational AFTER-ICU study.

BACKGROUND: Sustained new-onset atrial fibrillation (AF) in the intensive care unit has been reported to be associated with poor outcomes. However, in critical illness, whether rhythm-control therapy can achieve sinus rhythm (SR) restoration is unknown. This study aimed to assess the impact of rhythm-control therapy on SR restoration for new-onset AF in critically ill patients. METHODS: This post-hoc analysis of a prospective multicenter observational study involving 32 Japan intensive care units compared patients with and without rhythm-control therapy for new-onset atrial fibrillation (AF) and conducted a multivariable analysis using Cox proportional hazards regression analysis including rhythm-control therapy as a time-varying covariate for SR restoration. RESULTS: Of 423 new-onset AF patients, 178 patients (42%) underwent rhythm-control therapy. Among those patients, 131 (31%) underwent rhythm-control therapy within 6 h after AF onset. Magnesium sulphate was the most frequently used rhythm-control drug. The Cox proportional hazards model for SR restoration showed that rhythm-control therapy had a significant positive association with SR restoration (adjusted hazard ratio: 1.46; 95% confidence interval: 1.16-1.85). However, the rhythm-control group had numerically higher hospital mortality than the non-rhythm-control group (31% vs. 23%, p = 0.09). CONCLUSIONS: Rhythm-control therapy for new-onset AF in critically ill patients was associated with SR restoration. However, patients with rhythm-control therapy had poorer prognosis, possibly due to selection bias. These findings may provide important insight for the design and feasibility of interventional studies assessing rhythm-control therapy in new-onset AF.

Frequency and Risk Factors for Reverse Triggering in Pediatric Acute Respiratory Distress Syndrome during Synchronized Intermittent Mandatory Ventilation.

Rationale: Reverse triggering (RT) occurs when respiratory effort begins after a mandatory breath is initiated by the ventilator. RT may exacerbate ventilator-induced lung injury and lead to breath stacking.Objectives: We sought to describe the frequency and risk factors for RT among patients with acute respiratory distress syndrome (ARDS) and identify risk factors for breath stacking.Methods: We performed a secondary analysis of physiologic data from children on synchronized intermittent mandatory pressure-controlled ventilation enrolled in a single-center randomized controlled trial for ARDS. When children had a spontaneous effort on esophageal manometry, waveforms were recorded and independently analyzed by two investigators to identify RT.Results: We included 81,990 breaths from 100 patient-days and 36 patients. Overall, 2.46% of breaths were RTs, occurring in 15/36 patients (41.6%). A higher tidal volume and a minimal difference between neural respiratory rate and set ventilator rate were independently associated with RT (P = 0.001) in multivariable modeling. Breath stacking occurred in 534 (26.5%) of 2,017 RT breaths and in 14 (93.3%) of 15 patients with RT. In multivariable modeling, breath stacking was more likely to occur when total airway Δpressure (peak inspiratory pressure - positive end-expiratory pressure [PEEP]) at the time patient effort began, peak inspiratory pressure, PEEP, and Δpressure were lower and when patient effort started well after the ventilator-initiated breath (higher phase angle) (all P < 0.05). Together, these parameters were highly predictive of breath stacking (area under the curve, 0.979).Conclusions: Patients with higher tidal volume who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking >25% of the time.Clinical trial registered with ClinicalTrials.gov (NCT03266016).

Prognosis of pathogen-proven acute respiratory distress syndrome diagnosed from a protocol that includes bronchoalveolar lavage: a retrospective observational study.

BACKGROUND: To treat patients with acute respiratory distress syndrome (ARDS), it is important to diagnose specific lung diseases and identify common risk factors. Our facility focuses on using bronchoalveolar lavage (BAL) to identify precise risk factors and determine the causative pathogen of ARDS within 24 h of intensive care unit (ICU) admission. This study evaluated the prognoses of pathogen-proven ARDS patients who were diagnosed or identified with risk factors using a diagnostic protocol, which included BAL, compared with the prognoses of pathogen-unproven ARDS patients. METHODS: This retrospective observational study was conducted in the ICU at a tertiary hospital from October 2015 to January 2019. We enrolled patients with respiratory distress who were on mechanical ventilation for more than 24 h in the ICU and who were subjected to our diagnostic protocol. We compared the disease characteristics and mortality rates between pathogen-proven and pathogen-unproven ARDS patients. RESULTS: Seventy ARDS patients were included, of whom, 50 (71%) had pathogen-proven ARDS as per our protocol. Mortality rates in both the ICU and the hospital were significantly lower among pathogen-proven ARDS patients than among pathogen-unproven ARDS patients (10% vs. 50%, p = 0.0006; 18% vs. 55%, p = 0.0038, respectively). Pathogen-proven ARDS patients were independently associated with hospital survival (adjusted hazard ratio, 0.238; 95% confidence interval, 0.096-0.587; p = 0.0021). CONCLUSIONS: Our diagnostic protocol, which included early initiation of BAL, enabled diagnosing pathogen-proven ARDS in 71% of ARDS patients. These patients were significantly associated with higher hospital survival rates. The diagnostic accuracy of our diagnostic protocol, which includes BAL, remains unclear.

Impact of inappropriate empiric antimicrobial therapy on mortality in pediatric patients with bloodstream infection: a retrospective observational study.

Inappropriate empiric antibiotic therapy for bloodstream infection could be associated with mortality in adults. However, data for pediatric patients have been scarce. The purpose of this study was to investigate the impact of an inappropriate empiric antibiotic therapy on mortality in pediatric patients with bloodstream infection. We retrospectively analyzed the data of pediatric patients with consecutive positive blood culture in the university hospital between 2007 and 2016. The association between the use of inappropriate empiric therapy and mortality was investigated. A total of 247 bacteremia events in 223 pediatric patients were analyzed. Overall, 208 (84%) events were hospital acquired and 16 (6%) patients died within 28 days. The most frequent causative microorganisms were Gram-positive bacteria (150 events, 61%), followed by Gram-negative bacteria (90 events, 36%) and Candida spp. (7 events, 3%). Inappropriate empiric antibiotic therapy was prescribed within 48 h in 34 (16%) events. Significantly better 28-day survival rates were obtained in patients that received appropriate empiric antibiotic therapy compared with those who received inappropriate therapy (p = 0.004). Multivariate Cox regression analysis showed that inappropriate empiric antibiotic therapy was an independent prognostic factor of 28-day mortality (hazard ratio, 4.39; 95% confidence interval, 1.48-11.94; p = 0.01), after adjusting for age and McCabe score. Inappropriate empiric antibiotic therapy was associated with poor 28-day mortality in pediatric patients with bloodstream infection. Strategies to increase appropriate selection of empiric antibiotic therapy might be an option for improving survival in pediatric patients with bloodstream infection.