The Japan Society for Surgical Infection: guidelines for the prevention, detection, and management of gastroenterological surgical site infection, 2018.

BACKGROUND: The guidelines for the prevention, detection, and management of gastroenterological surgical site infections (SSIs) were published in Japanese by the Japan Society for Surgical Infection in 2018. This is a summary of these guidelines for medical professionals worldwide. METHODS: We conducted a systematic review and comprehensive evaluation of the evidence for diagnosis and treatment of gastroenterological SSIs, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Modifications were made to the guidelines in response to feedback from the general public and relevant medical societies. RESULTS: There were 44 questions prepared in seven subject areas, for which 51 recommendations were made. The seven subject areas were: definition and etiology, diagnosis, preoperative management, prophylactic antibiotics, intraoperative management, perioperative management, and wound management. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the results of the meta-analysis, recommendations were graded using the Delphi method to generate useful information. The final version of the recommendations was published in 2018, in Japanese. CONCLUSIONS: The Japanese Guidelines for the prevention, detection, and management of gastroenterological SSI were published in 2018 to provide useful information for clinicians and improve the clinical outcome of patients.

Current status of post-operative infections due to antimicrobial-resistant bacteria after digestive tract surgery in Japan: Japan Postoperative Infectious Complications Survey in 2015 (JPICS'15).

PURPOSE: We herein report the findings of the Japan Postoperative Infectious Complication Survey in 2015 (JPICS'15), which evaluated the rate of post-operative infections and colonization due to antimicrobial-resistant (AMR) bacteria after digestive tract surgery. METHODS: This survey by the Japan Society of Surgical Infection included patients undergoing digestive tract surgery at 28 centers between September 2015 and March 2016. Data included patient background characteristics, type of surgery, contamination status, and type of post-operative infections, including surgical site infections (SSIs), remote infections (RIs), and colonization. RESULTS: During the study period, 7,565 surgeries (of 896 types) were performed; among them, 905 cases demonstrated bacteria after digestive tract surgery. The survey revealed that post-operative infections or colonization by AMR bacteria occurred in 0.9% of the patient cohort, constituting 7.5% of post-operative infections, including 5.6% of SSIs and 1.8% of RIs. Extended-spectrum ß-lactamase-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the predominant AMR bacteria isolated from patients after digestive tract surgery. Patients infected with AMR bacteria had a poor prognosis. CONCLUSION: Our results reveal that 7.5% of the post-operative infections were due to AMR bacteria, indicating the need for antibacterial coverage against AMR bacteria in patients with critical post-operative infections.

Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial.

PURPOSES: This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection. METHOD: We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI. RESULTS: Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, - 0.30; 90% CI - 4.80 to 4.19% [95% CI - 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable. CONCLUSION: To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.

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.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos).

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018.

The Tokyo Guidelines 2013 (TG13) include new topics in the biliary drainage section. From these topics, we describe the indications and new techniques of biliary drainage for acute cholangitis with videos. Recently, many novel studies and case series have been published across the world, thus TG13 need to be updated regarding the indications and selection of biliary drainage based on published data. Herein, we describe the latest updated TG13 on biliary drainage in acute cholangitis with meta-analysis. The present study showed that endoscopic transpapillary biliary drainage regardless of the use of nasobiliary drainage or biliary stenting, should be selected as the first-line therapy for acute cholangitis. In acute cholangitis, endoscopic sphincterotomy (EST) is not routinely required for biliary drainage alone because of the concern of post-EST bleeding. In case of concomitant bile duct stones, stone removal following EST at a single session may be considered in patients with mild or moderate acute cholangitis except in patients under anticoagulant therapy or with coagulopathy. We recommend the removal of difficult stones at two sessions after drainage in patients with a large stone or multiple stones. In patients with potential coagulopathy, endoscopic papillary dilation can be a better technique than EST for stone removal. Presently, balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is used as the first-line therapy for biliary drainage in patients with surgically altered anatomy where BE-ERCP expertise is present. However, the technical success rate is not always high. Thus, several studies have revealed that endoscopic ultrasonography-guided biliary drainage (EUS-BD) can be one of the second-line therapies in failed BE-ERCP as an alternative to percutaneous transhepatic biliary drainage where EUS-BD expertise is present.

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.

Socioeconomic effects of surgical site infection after cardiac surgery in Japan.

PURPOSE: Surgical site infection (SSI) increases medical costs and prolongs hospitalization; however, there has been no multicenter study examining the socioeconomic effects of SSI after cardiovascular surgery in Japan. METHODS: A retrospective 1:1 matched, case-controlled study on hospital stay and health care expenditure after cardiovascular surgery was performed in four hospitals. Patients selected for the study had undergone coronary artery bypass grafting and/or valve surgery between April, 2006 and March, 2008. Data were obtained for 30 pairs of patients. RESULTS: The mean postoperative stay for the SSI group was 49.1 days, being 3.7 times longer than that for the non-SSI group. The mean postoperative health care expenditure for the SSI group was ¥ 2,763,000 (US$27,630), being five times higher than that for the non-SSI group. Charges for drug infusion and hospitalization for inpatient care were significantly higher for the SSI group than for the non-SSI group. The increased health care expenditure was mainly attributed to the cost of antibiotics and antimicrobial agents. CONCLUSION: SSI after cardiovascular surgery not only prolonged the length of hospital stay, but also increased medical expenditure. Thus, the prevention of SSI after cardiovascular surgery is of great socioeconomic importance.

TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis.

In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were first published in the Journal of Hepato-Biliary-Pancreatic Surgery. The fundamental policy of TG07 was to achieve the objectives of TG07 through the development of consensus among specialists in this field throughout the world. Considering such a situation, validation and feedback from the clinicians' viewpoints were indispensable. What had been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. In June 2010, we set up the Tokyo Guidelines Revision Committee for the revision of TG07 (TGRC) and started the validation of TG07. We also set up new diagnostic criteria and severity assessment criteria by retrospectively analyzing cases of acute cholangitis and cholecystitis, including cases of non-inflammatory biliary disease, collected from multiple institutions. TGRC held meetings a total of 35 times as well as international email exchanges with co-authors abroad. On June 9 and September 6, 2011, and on April 11, 2012, we held three International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines. Through these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria, and the new severity assessment criteria, new flowcharts of the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been added, new recommendations for gallbladder drainage and antimicrobial therapy, and the role of surgical intervention. Management bundles for acute cholangitis and cholecystitis were introduced for effective dissemination with the level of evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the grade of recommendations. TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The bundles for the management of acute cholangitis and cholecystitis are presented in a separate section in TG13. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Nationwide surveillance of antimicrobial susceptibility patterns of pathogens isolated from surgical site infections (SSI) in Japan.

To investigate the trends of antimicrobial resistance in pathogens isolated from surgical site infections (SSI), a Japanese surveillance committee conducted the first nationwide survey. Seven main organisms were collected from SSI at 27 medical centers in 2010 and were shipped to a central laboratory for antimicrobial susceptibility testing. A total of 702 isolates from 586 patients with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4 %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among S. aureus was 72.0 %. Vancomycin MIC 2 µg/ml strains accounted for 9.7 %. In Escherichia coli, 11 of 95 strains produced extended-spectrum ß-lactamase (Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains produced metallo-ß-lactamase. In P. aeruginosa, the resistance rates were 7.4 % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group, the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and IPM, and 0 % to metronidazole (Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0 %). MIC90 of P. aeruginosa isolated 15 days or later after surgery rose in TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of Anesthesiologists (ASA) score ≥3, the resistance rates of P. aeruginosa to TAZ/PIPC and CAZ were higher than in patients with ASA ≤2. The data obtained in this study revealed the trend of the spread of resistance among common species that cause SSI. Timing of isolation from surgery and the patient's physical status affected the selection of resistant organisms.

Length of stay and cost for surgical site infection after abdominal and cardiac surgery in Japanese hospitals: multi-center surveillance.

PURPOSE: This study evaluated the influence of surgical site infections (SSIs) after abdominal or cardiac surgery on the post-operative duration of hospitalization and cost. METHODS: A retrospective 1:1 matched case-control study of length of stay and healthcare expenditures for patients who were discharged from nine hospitals, between April 1, 2006 and March 31, 2008, after undergoing abdominal or cardiac surgery and who did and did not have a SSI. RESULTS: Information was obtained from 246 pairs of patients who had undergone abdominal surgery and 27 pairs of patients who had undergone cardiac surgery. Overall, the mean post-operative hospitalization was 20.7 days longer and the mean post-operative healthcare expenditure was $8,791 higher in the SSI group than for the SSI-free group. Among the patients who had undergone abdominal surgery, development of SSI extended the average hospitalization by 17.6 days and increased the average healthcare expenditure by $6,624. Among the patients who had undergone cardiac surgery, SSI extended the post-operative hospitalization by an average of 48.9 days and increased the post-operative healthcare expenditure by an average of $28,534. CONCLUSIONS: Under the current healthcare system in Japan, the development of SSI after abdominal surgery necessitates extension of hospitalization two-fold and increases the post-operative healthcare expenditure 2.5-fold. Development of SSI after cardiac surgery necessitates extension of hospitalization fourfold and increases the healthcare expenditure six-fold.

Impact of surgical site infection after colorectal surgery on hospital stay and medical expenditure in Japan.

PURPOSE: To clarify the impact of surgical site infection (SSI) after colorectal surgery on the length of hospital stay and medical expenditure in Japan. METHODS: This was a multi-center, retrospective-matched case-control study. RESULTS: The total number of patients enrolled was 334 (167 case/control pairs). The average hospital stay after surgery was prolonged by 17.8 days (95% CI 11.9-23.5) and the average medical cost after surgery was increased by $5,938 (95% CI 3,610-8,367) in the SSI group versus the non-SSI group. Hospital charges comprised the largest among all cost categories and accounted for 53% of the additional cost. The hospital stay and medical costs both increased proportionately to the depth of the SSI, from 4.4 days and $608 for superficial incisional SSI, to 39.2 days and $14,448 for organ/space SSI. SSI caused by MRSA prolonged the hospital stay by 19.3 days and incurred an additional cost of $7,015. CONCLUSIONS: SSI clearly prolonged the hospital stay and increased medical costs. The numerical values revealed by this study reinforce the medical-economic importance of instigating preventive measures against SSI.

Evaluation of the efficacy and safety of intravenous ciprofloxacin versus meropenem in the treatment of postoperative infection.

Therapeutic options for postoperative infection in gastrointestinal surgery are limited. To identify new treatment alternatives, the Japan Society for Surgical Infection conducted a multicenter prospective, randomized, controlled clinical trial comparing the efficacy of intravenous ciprofloxacin (CIP IV) and intravenous meropenem (MEM IV). Between July 2005 and May 2008, the trial recruited patients who developed postoperative infection or had suspected infectious systemic inflammatory response syndrome after elective clean-contaminated gastrointestinal surgery. All patients had received prophylactic postoperative antibiotic treatment. Patients received either intravenous CIP IV 300 mg b.i.d. or MEM IV 500 mg b.i.d. A total of 205 patients from 31 institutions were enrolled. Of these, 101 were randomized to CIP IV and 104 to MEM IV. There were 100 and 102 in the intent-to-treat (ITT)/safety population and 75 and 77 in the per-protocol (PP) population. There was no significant difference between CIP IV and MEM IV in terms of clinical efficacy, bacteriological efficacy, incidence of adverse drug reactions, duration of antimicrobial treatment, or relapse/reactivation. Overall clinical success PP population) was high in both treatment groups: 85.3% (64/75) for CIP IV and 89.6% (69/77) for MEM IV, although the non-inferiority of CIP IV was not demonstrated (difference -4.3%, 95% CI -14.8, 6.2). In patients who had undergone upper gastrointestinal surgery, success was 88.5% (23/26) for CIP IV and 85.2% (23/27) for MEM IV. Intravenous ciprofloxacin is as effective as intravenous meropenem in the empiric therapy of postoperative infection after gastrointestinal surgery.

Antimicrobial prophylaxis and colon preparation for colorectal surgery: Results of a questionnaire survey of 721 certified institutions in Japan.

PURPOSE: Antimicrobial prophylaxis (AMP) can reduce the risk of surgical site infection (SSI) in gastroenterological surgery; however, in Japan its use was not fully recognized before 2000. The first nationwide guideline was published in 2001, since when the use of AMP has improved gradually. We conducted this study to investigate the current implementation of AMP in colorectal surgery and adherence to recommended practices for preventing SSI in Japan. METHODS: A questionnaire survey was sent to hospitals accredited by the Japanese Society of Gastroenterological Surgery and the Japan Society for Surgical Infection (JSSI). The questionnaire focused on the AMP regimen used for colorectal surgery. RESULTS: Responses were received from 721 (58%) of the 1249 hospitals that were sent the survey. The initial AMP dose was administered within 1 h before incision at 94% of the responding institutions. AMP was discontinued within 24 h of surgery at only 10% of institutions. Second-generation cephalosporins were administered at 84% of the institutions. CONCLUSIONS: The appropriate use of AMP in colorectal surgery is incomplete in certified institutions in Japan. The fact that many institutions administer AMP for longer than recommended is a problem that needs to be addressed.

Evidence of intravenous immunoglobulin as a critical supportive therapy against Clostridium difficile toxin-mediated lethality in mice.

OBJECTIVES: Clostridium difficile produces toxins and is an aetiological organism of pseudomembranous colitis. Immunoglobulin is one of the treatment strategies against fulminant C. difficile infections, but the clinical evidence is still limited. We examined the efficacy of intravenous immunoglobulin (IVIg) in C. difficile toxin (CDT)-mediated lethality and cellular injury in mice. METHODS: Mice were intraperitoneally injected with 0.2 mL of filter-sterilized C. difficile culture supernatant (CDT preparation). The IVIg preparation was intravenously administered at several timepoints. We also examined alteration of intestinal permeability and an apoptosis marker in the gut. In in vitro experiments, HEp-2 cells were incubated with a CDT preparation in the presence or absence of the IVIg preparation, after which cell viability and lactate dehydrogenase release were examined. RESULTS: All control mice died by day 2 after injection of the CDT preparation. The maximum effects of IVIg (100% survival) were observed when the mice were treated with IVIg at the same time as injection of the CDT preparation. The IVIg effects were closely associated with improvement of intestinal vascular permeability and mucosal damage in the gut. In addition, reduction of an apoptosis marker (histone-associated DNA fragments) was demonstrated in the mice treated with IVIg. Interestingly, a smaller increase in histone-associated DNA fragments was observed in FasL-deficient mice treated with the CDT preparation compared with wild-type. CONCLUSIONS: These data demonstrated that IVIg may be protective against CDT-mediated lethality, when administered at the appropriate time. The present data also suggest an increase in intestinal permeability, probably through exaggeration of Fas/FasL-mediated apoptosis, as a key mechanism of C. difficile-mediated diseases.

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.

Involvement of endotoxin in the mortality of mice with gut-derived sepsis due to methicillin-resistant Staphylococcus aureus.

MRSA causes a wide diversity of diseases, ranging from benign skin infections to life-threatening diseases, such as sepsis. However, there have been few reports of the pathophysiology and mechanisms of sepsis resulting from the gut-derived origin of MRSA. Therefore, we established a murine model of gut-derived sepsis with MRSA and factors of MRSA sepsis that cause deterioration. We separated mice into four groups according to antibiotic treatment as follows: (i) ABPC 40 mg/kg; (ii) CAZ 80 mg/kg; (iii) CAZ 80 mg/kg + endotoxin 10 microg/mouse; and (iv) saline-treated control groups. Gut-derived sepsis was induced by i.p. injection of cyclophosphamide after colonization of MRSA strain 334 in the intestine. After the induction of sepsis, significantly more CAZ-treated mice survived compared with ABPC-treated and control groups. MRSA were detected in the blood and liver among all groups. Endotoxin levels were significantly lower in the CAZ-treated group compared to other groups. Inflammatory cytokine levels in the serum were lower in the CAZ-treated group compared to other groups. Fecal culture showed a lower level of colonization of E. coli in the CAZ-treated group compared to other groups. In conclusion, we found that CAZ-treatment ameliorates infection and suppresses endotoxin level by the elimination of E. coli from the intestinal tract of mice. However, giving endotoxin in the CAZ-treated group increased mortality to almost the same level as in the ABPC-treated group. These results suggest endotoxin released from resident E. coli in the intestine is involved in clinical deterioration resulting from gut-derived MRSA sepsis.

[Surgical site infection (SSI) and postoperative infection].

Infectious diseases, surgical site infections (SSI) in particular are the most popular perioperative complications, and not only the treatment but also prevention is extremely important. The inappropriate use of antibiotic prophylaxis in surgical patients accelerated the development of drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) or multiple-drug resistant Pseudomonas aeruginosa (MDRP) infections. With this as a turning point, improvements in the choice and the usage of prophylactic antibiotic agents are being discussed in Japan. The importance of the preservation of the normal intestinal bacterial flora and the proper usage of the antibiotics became clear and guidelines have been established. It is important to make a distinction between prophylactic and therapeutic antibiotic administration in the perioperative period. The anti-cross infection measure with the observance of Standard Precautions is also important in infection control.