Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome.

Oxidative stress plays a key role in the pathophysiology of post-cardiac arrest syndrome. Molecular hydrogen reduces oxidative stress and exerts anti-inflammatory effects in an animal model of cardiac arrest. However, its effect on human post-cardiac arrest syndrome is unclear. We consecutively enrolled five comatose post-cardiac arrest patients (three males; mean age, 65 ± 15 years; four cardiogenic, one septic cardiac arrest) and evaluated temporal changes in oxidative stress markers and cytokines with inhaled hydrogen. All patients were treated with target temperature management. Hydrogen gas inhalation (2% hydrogen with titrated oxygen) was initiated upon admission for 18 h. Blood hydrogen concentrations, plasma and urine oxidative stress markers (derivatives of reactive oxygen metabolites, biological antioxidant potential, 8-hydroxy-2'-deoxyguanosine, N ɛ-hexanoyl-lysine, lipid hydroperoxide), and cytokines (interleukin-6 and tumor necrosis factor-α) were measured before and 3, 9, 18, and 24 h after hydrogen gas inhalation. Arterial hydrogen concentration was measurable and it was equilibrated with inhaled hydrogen. Oxidative stress was reduced and cytokine levels were unchanged in cardiogenic patients, whereas oxidative stress was unchanged and cytokine levels were diminished in the septic patient. The effect of inhaled hydrogen on oxidative stress and cytokines in comatose post-cardiac arrest patients remains indefinite because of methodological weaknesses.

Early Lactate Clearance Is Associated With Improved Outcomes in Patients With Postcardiac Arrest Syndrome: A Prospective, Multicenter Observational Study (SOS-KANTO 2012 Study).

OBJECTIVES: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest. DESIGN: Ad hoc data analysis of a prospective, multicenter observational study. SETTING: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013. PATIENTS: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified. INTERVENTIONS: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement. MEASUREMENTS AND MAIN RESULTS: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14-4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46-3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01-2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission. CONCLUSIONS: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.

Sudden Death Phenomenon While Bathing in Japan　- Mortality Data.

BACKGROUND: Bath-related sudden cardiac arrest frequently occurs in Japan, but the mortality data have not been sufficiently reported.Methods and Results:This prospective cross-sectional observational study was conducted in the Tokyo Metropolis, Saga Prefecture and Yamagata Prefecture between October 2012 and March 2013 (i.e., in winter). We investigated the data for all occurrences in these areas for which the emergency medical system needed to be activated because of an accident or acute illness related to bathing. Emergency personnel enrolled the event when activation of the emergency medical system was related to bathing. Of the 4,599 registered bath-related events, 1,527 (33%) were identified as bath-related cardiac arrest events. Crude mortality (no. deaths per 100,000) during the observational period was 10.0 in Tokyo, 11.6 in Yamagata and 8.5 in Saga. According to the mortality data for age and sex, the estimated number of bath-related deaths nationwide was 13,369 in winter, for the 6 months from October (95% CI: 10,862-16,887). Most cardiac arrest events occurred in tubs filled with water with the face submerged in the water. This suggests that drowning plays a crucial role in the etiology of such phenomena. CONCLUSIONS: The estimated nationwide number of deaths was 13,369 (95% CI: 10,862-16,887) in winter, for the 6 months from October. Crude mortality during the winter season was 10.0 in Tokyo, 11.6 in Yamagata and 8.5 in Saga.

The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction　- First Pilot Study in Humans.

BACKGROUND: Hydrogen gas inhalation (HI) reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model of acute myocardial infarction (AMI). We designed a prospective, open-label, rater-blinded clinical pilot study in patients experiencing ST-elevated MI (STEMI).Methods and Results:The 20 patients with an initial diagnosis of STEMI were assigned to either an HI group (1.3% H2with 26% oxygen) or a control group (26% oxygen). There were no HI-related severe adverse events. In the full analysis set, the cardiac salvage index as evaluated using cardiac magnetic resonance imaging at 7 days after primary percutaneous coronary intervention (PCI), showed no significant between-group difference (HI: 50.0±24.3%; control: 60.1±20.1%; P=0.43). However, the improvement from day 7 in the HI group was numerically greater than that in the control group in some of the surrogate outcomes at 6-month follow-up, including the LV stroke volume index (HI: 9.2±7.1 mL/m2; control: -1.4±7.2 mL/m2; P=0.03) and the LV ejection fraction (HI: 11.0%±9.3%; control: 1.7%±8.3%; P=0.11). CONCLUSIONS: The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome　- First-in-Human Pilot Study.

BACKGROUND: Hydrogen gas inhalation (HI) ameliorates cerebral and cardiac dysfunction in animal models of post-cardiac arrest syndrome (PCAS). HI for human patients with PCAS has never been studied. METHODS AND RESULTS: Between January 2014 and January 2015, 21 of 107 patients with out-of-hospital cardiac arrest achieved spontaneous return of circulation. After excluding 16 patients with specific criteria, 5 patients underwent HI together with target temperature management (TTM). No undesirable effects attributable to HI were observed and 4 patients survived 90 days with a favorable neurological outcome. CONCLUSIONS: HI in combination with TTM is a feasible therapy for patients with PCAS. (Circ J 2016; 80: 1870-1873).

Prognostic factors of Streptococcus pneumoniae infection in adults.

OBJECTIVES: The mortality of severe sepsis has markedly decreased since the implementation of the Surviving Sepsis Campaign guidelines. The next logical step is to examine the necessity of individualized management guidelines for targeted therapy against specific bacteria. Streptococcus pneumoniae is the leading cause of community-acquired severe sepsis; however, little is known regarding the prognostic factors in adult patients with S pneumoniae sepsis. We aimed to identify prognostic factors in patients with S pneumoniae sepsis and to explore a subgroup of patients at high risk for death with detailed Sequential Organ Failure Assessment (SOFA) score analysis. METHODS: We retrospectively reviewed the records of patients with S pneumoniae infection treated between 1st January 2006 and 31st July 2012. We identified prognostic factors for 28-day mortality using univariate and multivariate logistic regression models. RESULTS: Of 171 patients (median age, 72 years) with S pneumoniae infection who were included in this study, the 28-day mortality was 17% (29/171). The SOFA score (odds ratio, 2.25; 95% confidence interval, 1.60-3.18; P < .001) and bacteremia (odds ratio, 19.0; 95% confidence interval, 4.06-90.20; P < .001) were identified as prognostic factors for the 28-day mortality. In a subgroup analysis with a cutoff value of the SOFA score determined by receiver operating characteristic analysis, patients with bacteremia and a SOFA score of at least 7 had a significantly higher mortality than did patients without bacteremia and a SOFA score lower than 7 (84% vs 0%, respectively). CONCLUSIONS: Bacteremia and a SOFA score at least 7 were independent prognostic factors of poor outcome in S pneumoniae sepsis.

Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management.

BACKGROUND: We have previously shown that hydrogen (H2) inhalation, begun at the start of hyperoxic cardiopulmonary resuscitation, significantly improves brain and cardiac function in a rat model of cardiac arrest. Here, we examine the effectiveness of this therapeutic approach when H2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM). METHODS AND RESULTS: Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, post-cardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O2 and normothermia (control); mechanically ventilated with 26% O2, 1.3% H2, and normothermia (H2); mechanically ventilated with 26% O2 and TTM (TTM); and mechanically ventilated with 26% O2, 1.3% H2, and TTM (TTM+H2). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in the H2 and TTM groups, and 85.7% in the TTM+H2 group. Combined therapy of TTM and H2 inhalation was superior to TTM alone in terms of neurological deficit scores at 24, 48, and 72 hours after ROSC, and motor activity at 7 days after ROSC. Neuronal degeneration and microglial activation in a vulnerable brain region was suppressed by both TTM alone and H2 inhalation alone, with the combined therapy of TTM and H2 inhalation being most effective. CONCLUSIONS: H2 inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H2 inhalation was more effective than TTM alone.

Inhalation of Hydrogen Gas Is Beneficial for Preventing Contrast-Induced Acute Kidney Injury in Rats.

Background: The present study aimed at investigating the effect of a novel antioxidant, hydrogen (H2) gas, on the severity of contrast-induced acute kidney injury (CIAKI) in a rat model. Methods: CIAKI was induced in rats by intravenous injection of a contrast medium, Ioversol, in addition to reagents inhibiting prostaglandin and nitric oxide synthesis. During the injection of these reagents, the rats inhaled H2 gas or control gas. Results: One day after the injection, serum levels of urea nitrogen were significantly lower in H2 gas-inhaling CIAKI rats (17.6 ± 2.3 mg/dl) than those in control gas-treated CIAKI rats (36.0 ± 7.3 mg/dl), although they both were elevated as compared to untreated rats (14.9 ± 0.9 mg/dl). Consistently, creatinine clearance in H2 gas-treated CIAKI rats was higher than that in control gas-treated counterparts. Renal histological analysis revealed that the formation of proteinaceous casts and tubular necrosis was improved by H2 gas inhalation. Mechanistic analyses showed that inhalation of H2 gas significantly reduced renal cell apoptosis, expression of cleaved caspase 3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in injured kidneys. Conclusion: Results suggest that H2 gas inhalation is effective in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis and oxidative stress. © 2015 S. Karger AG, Basel.

Estimated cerebral oxyhemoglobin as a useful indicator of neuroprotection in patients with post-cardiac arrest syndrome: a prospective, multicenter observational study.

INTRODUCTION: Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS). METHODS: The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurological status at 90 days. RESULTS: We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurological outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward elimination method confirmed that the oxy-Hb level was a significant predictor of good neurological outcomes (adjusted odds ratio: 1.27, 95% confidence interval (CI): 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurological outcomes (AUC: 0.87, 95% CI: 0.83 to 0.91; sensitivity: 77.3%; specificity: 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess according to AUC analysis. The significant trend for good neurological outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation upon hospital arrival (1st quartile: 0%; 2nd quartile: 16.7%; 3rd quartile: 29.4%; 4th quartile: 53.3%, P <0.05). CONCLUSIONS: The cerebral oxy-Hb level may predict neurological outcomes and is a simple and excellent indicator of neuroprotection in patients with PCAS. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000005065. Registered 1 April 2011.

Penetration of micafungin into the burn eschar in patients with severe burns.

Micafungin (MCFG) concentrations in the plasma and in burn eschar were investigated after daily intravenous infusion (1 h) of MCFG (200 mg) in three patients with severe burns. MCFG treatment was initiated more than 72 h after the burn injuries. The MCFG concentrations in the plasma were determined at the end of the first administration of MCFG, immediately before the second dosing, at the end of the MCFG infusion after at least 4 days from the initial treatment, and immediately before the subsequent dosing using high-performance liquid chromatography. In addition, the trough levels in burn eschar after both the initial administration and repeated administration were measured. The peak and trough levels in the plasma were comparable to or slightly lower than the reported values in healthy volunteers. The mean (range) MCFG concentrations in the burn eschar after initial administration and repeated administration were 1.41 µg/mL (<0.1-3.98 µg/mL) and 6.65 µg/mL (1.10-14.81 µg/mL), respectively. In most cases, the MCFG concentrations in the burn eschar, especially after repeated administration, were higher than the reported MIC90 of MCFG against the clinically important pathogenic species of Candida and Aspergillus. These results suggest that MCFG is capable of penetrating burn eschar.

Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening vascular disease without effective pharmaceutical therapy. Matrix metalloproteinases (MMPs) are implicated in the development of chronic vascular diseases including aneurysm, but the key effectors and mechanism of action remain unknown. To define further the role of MMPs in AAD, we screened circulating MMPs in AAD patients, and then generated a novel mouse model for AAD to characterize the mechanism of action. METHODS AND RESULTS: MMP9 and angiotensin II were elevated significantly in blood samples from AAD patients than in those from the patients with nonruptured chronic aortic aneurysm or healthy volunteers. Based on the findings, we established a novel AAD model by infusing angiotensin II to immature mice that had been received a lysyl oxidase inhibitor, ß-aminopropionitrile monofumarate. AAD was developed successfully in the thoracic aorta by angiotensin II administration to ß-aminopropionitrile monofumarate-treated wild-type mice, with an incidence of 20%, 80%, and 100% after 6, 12, and 24 hours, respectively. Neutrophil infiltrations were observed in the intima of the thoracic aorta, and the overexpression of MMP9 in the aorta was demonstrated by reverse transcription polymerase chain reaction, gelatin zymography, and immunohistochemistry. The incidence of AAD was reduced significantly by 40% following the administration of an MMP inhibitor and was almost blocked completely in MMP(-/-) mice without any influence on neutrophil infiltration. Neutrophil depletion by injection of anti-granulocyte-differentiation antigen-1 (anti-Gr-1) antibody also significantly decreased the incidence of AAD. CONCLUSIONS: These data suggest that AAD is initiated by neutrophils that have infiltrated the aortic intima and released MMP9 in response to angiotensin II.

Skew of plasma low- and high-density lipoprotein distributions to less dense subfractions in normotriglyceridemic chronic kidney disease patients on maintenance hemodialysis treatment.

BACKGROUND: Plasma levels of small, dense low-density lipoprotein (LDL) were reported to increase in chronic kidney disease (CKD) patients on hemodialysis (HD), but most of these patients were hypertriglyceridemic. Plasma levels of small, dense LDL are known to increase in hypertriglyceridemic subjects. Therefore, to investigate the direct effect of CKD on the distribution of LDL subfractions, we investigated the distribution of LDL subfractions in normotriglyceridemic CKD patients on HD. METHODS: The levels of plasma lipoprotein subfractions and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), which markedly influence the distributions of plasma LDL and high-density lipoprotein (HDL) subfractions, were compared between 40 HD patients and 40 normolipidemic controls. Plasma lipoproteins were subfractionated into seven subfractions by ultracentrifugation. RESULTS: Plasma levels of cholesterol (C) in remnant-like particle, which is equivalent to the triglyceride (TG)-rich lipoprotein remnant, were twice as high in HD patients as those in controls with matched TG levels. Plasma levels of C and TG in VLDL and IDL (intermediate density lipoprotein) were slightly higher in HD patients than in controls. The C/TG ratio of VLDL was significantly higher in HD patients than in controls. In comparison with the corresponding values in controls, the C and TG levels in low-density LDL and HDL2 in HD patients were high, whereas those in medium-density LDL, high-density LDL, and HDL3 were low. Plasma LCAT activity and CETP mass were lower in HD patients than in controls. CONCLUSION: Distribution of LDL and HDL skewed toward less dense fractions in normotriglyceridemic CKD patients on HD. A decrease in reverse C transport likely played an important role in these changes in the patients.

[Accidents during bathing].

Sudden death during bathing accounts for 10 to 15% of all out-of hospital cardiac arrests in Japan. Surveys in Tokyo revealed 1,085 victims of accidents during bathing transported by ambulance from October 1999 to March 2000. 53% of them were cardiac arrest and 25% were those who needed rescue from bath tub because of consciousness disturbance (rescued group). Clinical observation of the rescued group patients indicated they suffered from transient loss of consciousness probably because of elevated body temperature. The current hypothesis of the accidents during bathing is a unique type of heat illness exposed by high water temperature(41-43 degrees C). Geriatric population is vulnerable to the bathing induced heat illness.

Micafungin concentrations in the plasma and burn eschar of severely burned patients.

Micafungin concentrations in plasma and burn eschar after daily intravenous infusion (1 h) of micafungin (200 to 300 mg) were investigated for six patients with severe burns. Micafungin treatment was initiated more than 72 h after the burn injuries. The peak and trough levels in the plasma after the initial administration and repeated administrations for more than 4 days were comparable with or slightly lower than the reported values for healthy volunteers. Micafungin concentrations in the plasma and burn eschar were between 3.6 and >1,000 times higher than the reported MIC(90)s of micafungin against clinically important Candida and Aspergillus species.

Fever-induced ST-segment elevation in a syncopal patient with Brugada syndrome.

Brugada syndrome (BS) is associated with life-threatening ventricular tachyarrhythmias. Although a diagnosis of BS can be made by typical electrocardiographic (ECG) findings, these findings for BS vary depending on the patients' physiological conditions and are sometimes normalized or less evident. It is important for emergency physicians to recognize that the typical electrocardiographic findings of BS are not always manifested but sometimes are only unmasked in the presence of a specific condition.

[Indoor environment and heatstroke risk].

This paper describes the outline of heatstroke risk evaluation model for aged residents based on surveys done by the Heatstroke Surveillance Committee of Japanese Association for Acute Medicine and field measurements of indoor air temperature, humidity and so on. To reduce heatstroke of aged residents, promotion of thermal insulation, sun-shading, cross ventilation, air-condition of houses and living behavior of residents are needed.

The role of a real-time PCR technology for rapid detection and identification of bacterial and fungal pathogens in whole-blood samples.

The rapid diagnosis of pathogens and prompt initiation of appropriate antibiotic therapy are critical factors to reduce the morbidity and mortality associated with sepsis. In this study, we evaluated a multiplex polymerase chain reaction (PCR-M) test that detects bacteria and fungi in whole-blood specimens, comparing its features to those of a blood culture (BC). Following evaluation of the performance for sensitivity and specificity of PCR-M, 78 blood samples from 54 patients with suspected bacterial infections were evaluated. Whole-blood samples for PCR-M were collected at the same time as BC, and PCR-M results were compared with BC results. As a result, minimum sensitivity of the kit was 1-100 cfu/ml. The PCR-M test correctly identified specificity for 13 out of 14 strains blinded to the assay analyst. Of 78 blood samples examined, 56 (72%) were negative by both methods, and 22 (28%) were positive by at least one of the two methods. PCR-M detected organisms in 21 cases (27%) compared with 12 cases (15%) in BC. The correlation of positives between PCR-M and BC was 92% (11/12), and both methods identified the same organisms in these 11 cases. With higher positive rate compared with BC, PCR-M could detect and identify potentially significant microorganisms within a few hours by using a small volume of a single whole-blood sample. Early detection of microorganisms has the potential to facilitate early determination of appropriate treatment and antimicrobial selection.

[New evidences in the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care with Treatment Recommendations].

Key changes in Guideline 2010 by Japanese Resuscitation Council were described and the reasons of the change were explained based on 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care with Treatment Recommendations. In BLS, the value of chest compression was further emphasized and it became an initial skill of CPR In ALS, post resuscitation care was systemized by incorporating hypothermia, PCI, and other diagnostic and therapeutic modalities. Indication of hypothermia was further expanded to non-VF categories. Use of AED was expanded to infant. Education, Implementation and Teams were newly included as a chapter to promote the knowledge and skill of resuscitation science into the society.

Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit.

INTRODUCTION: Sepsis is a serious medical condition that requires rapidly administered, appropriate antibiotic treatment. Conventional methods take three or more days for final pathogen identification and antimicrobial susceptibility testing. We organized a prospective observational multicenter study in three study sites to evaluate the diagnostic accuracy and potential clinical utility of the SeptiFast system, a multiplex pathogen detection system used in the clinical setting to support early diagnosis of bloodstream infections. METHODS: A total of 212 patients, suspected of having systemic inflammatory response syndrome (SIRS) caused by bacterial or fungal infection, were enrolled in the study. From these patients, 407 blood samples were taken and blood culture analysis was performed to identify pathogens. Whole blood was also collected for DNA Detection Kit analysis immediately after its collection for blood culture. The results of the DNA Detection Kit, blood culture and other culture tests were compared. The chosen antimicrobial treatment in patients whose samples tested positive in the DNA Detection Kit and/or blood culture analysis was examined to evaluate the effect of concomitant antibiotic exposure on the results of these analyses. RESULTS: SeptiFast analysis gave a positive result for 55 samples, while 43 samples were positive in blood culture analysis. The DNA Detection Kit identified a pathogen in 11.3% (45/400) of the samples, compared to 8.0% (32/400) by blood culture analysis. Twenty-three pathogens were detected by SeptiFast only; conversely, this system missed five episodes of clinically significant bacteremia (Methicillin-resistant Staphylococcus aureus (MRSA), 2; Pseudomonas aeruginosa, 1; Klebsiella spp, 1; Enterococcus faecium, 1). The number of samples that tested positive was significantly increased by combining the result of the blood culture analysis with those of the DNA Detection Kit analysis (P = 0.01). Among antibiotic pre-treated patients (prevalence, 72%), SeptiFast analysis detected more bacteria/fungi, and was less influenced by antibiotic exposure, compared with blood culture analysis (P = 0.02). CONCLUSIONS: This rapid multiplex pathogen detection system complemented traditional culture-based methods and offered some added diagnostic value for the timely detection of causative pathogens, particularly in antibiotic pre-treated patients. Adequately designed intervention studies are needed to prove its clinical effectiveness in improving appropriate antibiotic selection and patient outcomes.