Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality. METHODS: We conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI). RESULTS: A total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were - 10 (95% confidence interval [CI]: -28 to 8, p = 0.282), - 7.8 (95% CI: -26 to 10, p = 0.401), and - 11 (95% CI: -26 to 3, p = 0.131), respectively. CONCLUSIONS: JSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

Prognostic value of serum high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of serum high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases. METHODS: We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system. RESULTS: Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, serum HMGB1 level of 8 ng/mL, and serum histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, serum HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: - 0.05 to 0.78, p = 0.08). CONCLUSIONS: Serum HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Emergency appendectomy versus elective appendectomy following conservative treatment for acute appendicitis: a multicenter retrospective clinical study by the Japanese Society for Abdominal Emergency Medicine.

PURPOSE: To establish the best treatment strategy for acute appendicitis. METHODS: We collected data on 2142 appendectomies performed in 2017 and compared the backgrounds and surgical outcomes of patients who underwent early surgery (ES) (< 48 h) with those managed with non-ES (> 48 h). We performed a risk factor analysis to predict postoperative complications and subgroup analysis to propose a standard treatment strategy. RESULTS: The incidence of postoperative complications was significantly higher in the ES group than in the non-ES group, and significantly lower in the laparoscopic surgery group than in the laparotomy group. Surgical outcomes, including the incidence of postoperative complications, were comparable after acute surgery (< 12 h) and subacute surgery (12-48 h), following antibiotic treatment. The risk factors for postoperative complications in the ES group were a higher age, history of abdominal surgery, perforation, high C-reactive protein level, histological evidence of gangrenous or perforated appendicitis, a long operation time, and intraoperative complications. The risk factors for postoperative complications in the non-ES group were perforation and unsuccessful conservative treatment. CONCLUSIONS: Non-early appendectomy is feasible for acute appendicitis but should be applied with care in patients with risk factors for postoperative complications or failure of pretreatment, including diabetes mellitus, abscess formation, and perforation.

Survey on the current status of the indication and implementation protocols for bile replacement in patients with external biliary drainage with special reference to infection control.

PURPOSE: This survey of bile replacement (BR) was conducted on patients with external biliary drainage to assess the current status of indication and implementation protocol of BR with special reference to infection control. METHODS: A 12-item questionnaire regarding the performance of perioperative BR was sent to 124 institutions in Japan. RESULTS: BR was performed in 29 institutions, and the indication protocol was introduced in 19. BR was performed preoperatively in 11 institutions, pre- and postoperatively in 12, and postoperatively in 6. The methods used for BR administration included oral intake (n = 10), nasogastric tube (n = 1), enteral nutrition tube (n = 3), oral intake and enteral nutrition tube (n = 6), oral intake or nasogastric tube (n = 2), nasogastric tube and enteral nutrition tube (n = 2), and oral intake or nasogastric tube and enteral nutrition tube (n = 5). In 10 of 29 institutions, isolation of multidrug-resistant organisms and a high bacterial load were considered contraindications for the use of BR. Seven institutions experienced environmental contamination. CONCLUSIONS: Given the different implementation of BR among institutions, the appropriate indication and protocols for BR should be established for infection control.

Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa.

BACKGROUND: In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear. METHODS: We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L. RESULTS: Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases. CONCLUSIONS: Hypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

Analysis of the association between resolution of disseminated intravascular coagulation (DIC) and treatment outcomes in post-marketing surveillance of thrombomodulin alpha for DIC with infectious disease and with hematological malignancy by organ failure.

BACKGROUND: Although disseminated intravascular coagulation (DIC) is life-threatening, any organ failure associated with DIC resolution and outcomes have been unclear. PATIENTS AND METHODS: A total of 2795 DIC patients (infection: 1990, hematological malignancy: 805) were analyzed in the post-marketing surveillance of thrombomodulin alpha (TM-α). The background factors of sequential organ failure assessment (SOFA) and antithrombin (AT) were investigated in DIC with infectious disease for their association with DIC resolution and outcome using κ statistics, indicating DIC resolution and survival or DIC non-resolution and non-survival. The same analyses were performed for total bilirubin, creatinine, lactate dehydrogenase, and underlying disease in DIC with hematological malignancy. RESULTS: In DIC with infectious disease, higher SOFA score severity was closely correlated with lower overall survival in both the DIC resolution and non-resolution groups, but AT activity was not. κ coefficients were 0.234, 0.295, and 0.311 for the SOFA score 0-6, 7-12, and 13-24 groups, respectively. In DIC with hematological malignancy, κ coefficients of total bilirubin were 0.251 and 0.434, and those of creatinine were 0.283 and 0.437 in the normal and abnormal groups, respectively, showing better concordance in the abnormal group than in the normal. Other factors had poor concordance. CONCLUSION: In DIC with infectious disease, DIC resolution is an important therapeutic target in patients who have higher SOFA score severity. In DIC with hematological malignancy, DIC resolution is similarly important in patients with abnormality of bilirubin and/or creatinine. TRIAL REGISTRATION: The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of the post-marketing surveillance data.

Significance of body temperature in elderly patients with sepsis.

BACKGROUND: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. METHODS: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study.

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134-2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia. CONCLUSIONS: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission.

BACKGROUND: Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. METHODS: This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. RESULTS: Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). CONCLUSIONS: Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Prognostic Accuracy of Quick SOFA is different according to the severity of illness in infectious patients.

BACKGROUND: Sepsis-3 proposed the quick Sequential Organ Failure Assessment (qSOFA) to identify sepsis patients likely to have poor outcome. The clinical utility of qSOFA still remains controversial because its predictive accuracy for mortality is quite different across the validation studies. We hypothesized that one of the major causes for these controversial findings was the heterogeneity in severity across the studies, and evaluated the association between severity of illness and the prognostic accuracy of qSOFA. MATERIALS AND METHODS: This was a post hoc analysis of a prospective nationwide cohort of consecutive adult patients with sepsis in 59 intensive care units in Japan. Regression trees analysis for survival was used to classify patients according to severity of illness as determined by SOFA score on registration. We conducted receiver operating characteristic (ROC) analyses and evaluated the differences in the area under the ROC curve (AUROC). As a subgroup analysis, we conducted the above evaluations in emergency department (ED) and non-ED patients separately. RESULTS: We included 1114 patients fulfilling the criteria and classified them into three subsets according to severity. The AUROC for mortality was significantly different according to the severity of illness (p = 0.007), with the highest AUROC being in the low-severity subset (patients with SOFA score ≤ 7). Interestingly, our subgroup analysis revealed that a significant difference in the AUROC of qSOFA was observed only in ED patients. CONCLUSION: This study suggested that lower severity of illness was associated with the relatively higher prognostic accuracy of qSOFA, especially in ED patients.

Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study.

BACKGROUND: Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. METHODS: This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. RESULTS: In total, 1184 patients (median age 73 years, interquartile range (IQR) 64-81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6-11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21-26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12-46) days. Approximately 37% of the patients were discharged home after recovery. CONCLUSION: Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742 . Registered on 16 November 2015.

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan.

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum ß-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with ß-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.

The approval of revised diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis.

As proposed diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis has been approved and revised, the contents and changes are informed.

Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: Comparison of data from nationwide surveillance studies conducted in 2010 and 2014-2015.

A nationwide survey was conducted in Japan from 2014 to 2015 to investigate the antimicrobial susceptibility of pathogens isolated from surgical site infections (SSI). The resulting data were compared with that obtained in an earlier survey, conducted in 2010. Seven main organisms were collected, and 883 isolates were studied. A significant reduction in methicillin resistance was observed among Staphylococcus aureus isolates, dropping from 72.5% in 2010 to 53.8% in 2014-2015 (p < 0.001). MRSA isolates with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL accounted for 1.2% of all MRSA isolates, which was significantly lower than in 2010 (9.7%, p = 0.029). Of the Escherichia coli isolates, 23.0% produced an extended spectrum ß-lactamase (ESBL) in the 2014-2015 survey, which was a significant increase from 9.5% in 2010 (p = 0.011). The geometric mean MICs for ESBL-producing isolates were 0.07 µg/mL for meropenem, 9.51 µg/mL for tazobactam/piperacillin, 0.15 µg/mL for flomoxef, and 1.56 µg/mL for gentamycin. There was a significant increase in the isolation rate of non-fragilis Bacteroides among Bacteroides fragilis group species between the two study periods (35.2% vs. 53.1%, p = 0.007). More than 90% of isolates belonging to the B. fragilis group remained susceptible to tazobactam/piperacillin, meropenem, and metronidazole. In contrast, lower levels of susceptibility were observed for cefmetazole (49.6%), moxifloxacin (61.9%), and clindamycin (46.9%). Non-fragilis Bacteroides isolates had lower rates of antibiotic susceptibility compared with B. fragilis. Overall, the surveillance data clarified trends in antimicrobial susceptibility for organisms commonly associated with SSI.

Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis.

Disseminated intravascular coagulation (DIC) is a serious disease that, in the presence of underlying disease, causes persistent, generalized, marked coagulation activation. Early treatment based on an appropriate diagnosis is very important for improving patients' prognosis, to which end diagnostic criteria play a key role. Several criteria have been proposed, but each has its strengths and weaknesses, and improved criteria are needed. Widespread use of coagulofibrinolytic markers has elucidated that the pathology of DIC differs greatly as a function of the underlying disease. Thus, discriminating use of DIC diagnostic criteria that take underlying diseases into account is important. DIC diagnostic criteria that are well known in Japan include the Japanese Ministry of Health and Welfare's old DIC diagnostic criteria (JMHW criteria), the International Society on Thrombosis and Haemostasis's DIC diagnostic criteria (ISTH criteria), and the Japanese Association for Acute Medicine's acute-stage DIC diagnostic criteria (JAAM criteria). Those criteria have their respective drawbacks: the sensitivity of the ISTH criteria is poor, the JAAM criteria cannot be applied to all underlying diseases, and the JMHW criteria have poor sensitivity in the case of infections, do not use molecular markers, and result in misdiagnosis. The Japanese Society on Thrombosis and Hemostasis's newly proposed provisional draft DIC diagnostic criteria (new criteria) use diagnostic criteria classifications of "hematopoietic disorder type", "infectious type", and "basic type" based on the underlying pathology. For the hematopoietic disorder type the platelet count is omitted from the score, while for the infectious type, fibrinogen is omitted from the score. Also, points are added if the platelet count decreases with time. In the new criteria, molecular markers and antithrombin activity have been newly included, and as a countermeasure for misdiagnosis, 3 points are deducted if there is liver failure. In this paper, we discuss various problems encountered with DIC diagnosis, and we describe the new criteria together with the events that led to their creation. These new diagnostic criteria take into account the underlying diseases of wide area, and we expect that they will serve clinicians well due to the above adaptations and improvements.