PubMed 2-Chloro-5,6-dihydro-7H-cyclopenta[b]pyridin-7-one2-Chloro-5,6-dihydro-7H-cyclopenta[b]pyridin-7-one ID:https://www.ncbi.nlm.nih.gov/pubmed/12711626 which causes systemic inflammatory response. IL-6 reaches a peak about 6 h after an insult. CRP and PCT are produced by the stimulation of IL-6; therefore, their peaks are delayed by 24?8 h after the peak of IL-6. The measurement of IL-6 enables early diagnosis of SIRS. Furthermore, IL-6 has been reported to reflect the severity and outcome in patients with sepsis [25-27]. PCT has been highlighted as the most promising biomarker; however, thus far, its usefulness has been reported mainly from Europe [28]. PCT measurement was also approved by health insurance in Japan from 2006. However, PCT is known to increase in noninfectious inflammation, including postsurgery or posttrauma; thus, its value for the diagnosis of sepsis is inconsistent [29]. The current cutoff values for CRP, IL-6, and PCT are presented in Additional file 1: Table III-1-1 as references for sepsis diagnosis. However, these values vary with different measurement methods, and therefore, the results should be interpreted with caution. IL-6 measurement is not yet covered by health insurance in Japan. Measurement of endotoxin is theoretically useful for diagnosing gram-negative bacterial infection; however, no measurement system for accurate detection has been established yet. Mainly turbidimetric time assay in Japan and endotoxin activity assay with Food and Drug Administration approval in Europe and the United States are used as endotoxin measurement methods. Both methods were reported to produce results that correlate with the severity of sepsis [30]; however, their sensitivity and specificity are far insufficient for the diagnosis of sepsis. However, current efforts to study the combination of several biomarkers may lead to the discovery 1-(Cyclopropylsulfonyl)-1,4-diazepane of a useful biomarker for s12998-016-0127-6 the diagnosis of sepsis.Abbreviations:ESICM: European Society of Intensive Care Medicine ATS: American Thoracic Society SIS: Surgical Infection Society CDC: Center for Disease Control and Prevention MODS: multiple organ dysfunction score SOFA: sequential organ failure assessmentDiagnosis of infectionCQ1: How should microbiological specimens be sampled? A1: We recommend obtaining blood culture samples before starting antimicrobial administration (1D). We recommend obtaining specimen samples from the suspected infectious source aseptically and immediately send them for Gram staining, culturing, and antimicrobial sensitivity testing (1D).Oda et al. Journal of Intensive Care 2014, 2:55 http://www.jintensivecare.com/content/2/1/Page 6 ofComment: As patients with severe sepsis/septic shock have a high possibility of having bacteremia, blood culture to determine the causative microorganism should be performed before empirical antimicrobials are administered [31]. Cerebrospinal fluid should be obtained in cases of suspected meningitis after excluding the possibility of intracranial hypertension. Bronchoscopic or blind bronchoalveolar lavage fluid samples should be obtained in cases of suspected ventilator-associated pneumonia for quantitative culture [32]. Tracheal aspiration might be acceptable if a patient has neither previous antimicrobial therapy nor risks of harboring antimicrobial-resistant pathogens [33,34]. In cases of suspected central venous catheter-associated bacteremia, we recommend obtaining PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22763976 two sets of blood culture samples, one set from the indwelling catheter and another set from the catheter tip [35]. Any sampling should be performed before, but without delay.