Efficacy and safety of tedizolid for the treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia in Japanese patients: Results from a subgroup analysis of a phase 3, randomized, double-blind study comparing tedizolid and linezolid.

INTRODUCTION: The results from the phase 3 study that evaluated the efficacy and safety of tedizolid phosphate, an oxazolidinone drug, for the treatment of gram-positive ventilated hospital-acquired bacterial pneumonia (vHABP)/ventilator-associated bacterial pneumonia (VABP) compared with linezolid (VITAL study), have been previously reported. We conducted a subgroup analysis to report the data obtained from Japanese patients enrolled in this study. METHODS: Patients aged ≥18 years with vHABP/VABP likely to be caused by gram-positive cocci were randomized 1:1 to tedizolid phosphate 200 mg once daily for 7 days or linezolid 600 mg twice daily for 10 days. In both treatment groups, patients with concurrent gram-positive bacteremia were treated for 14 days. Primary efficacy endpoints were day 28 all-cause mortality (ACM) and investigator-assessed clinical response at test-of-cure (TOC) in the intention-to-treat population. Safety outcomes included assessment of treatment-emergent adverse events. RESULTS: Fifty-three Japanese patients were randomized at received study drug (tedizolid, n = 28; linezolid, n = 25). Demographics and characteristics were generally similar between treatment groups. Rates of day 28 ACM were 10.7% and 20.0% with tedizolid and linezolid, respectively (difference, 9.3%; 95% CI, -10.1 to 28.7). Rates of investigator-assessed clinical cure at TOC were 78.6% and 72.0% with tedizolid and linezolid, respectively (difference, 6.6%; 95% CI, -16.7 to 29.8). Tedizolid phosphate was generally well tolerated and no new safety concerns were observed in the Japanese subgroup. CONCLUSION: The results from this subgroup analysis suggest generally favorable efficacy and safety of tedizolid in adult Japanese patients with vHABP/VABP. (ClinicalTrials.gov identifier: NCT02019420).

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.

Impact of postoperative remote infection on length of stay and medical costs in hospitals in Japan.

PURPOSE: To analyze the impact of postoperative remote infections (PRIs) on medical expenditure. METHODS: The subjects of this retrospective study were 338 patients who had undergone gastroenterological surgery at one of the 20 Japanese institutions within the Japan Society for Surgical Infection (JSSI) and mainly authorized as educational institutions. The patients were allocated to 169 pairs of those with a PRI (PRI (+) group) matched with those without a PRI (PRI (-) group). PRIs included pneumonia, urinary tract infection (UTI), catheter-associated blood stream infection (CA-BSI), and antibiotic-associated enteritis. RESULTS: SSI developed in 74 of the 338 patients (22 without PRI and 52 with PRI). The SSI incidence was significantly higher in the PRI (+) group (p < 0.001). The difference in the median postoperative length of hospital stay was 15 days, indicating a significant prolongation in the PRI (+) group (p < 0.001). The PRI (+) group also had a higher rate of inter-hospital transfer (p < 0.01) and mortality (p < 0.001). Similarly, the difference in median postoperative medical fees was $6832.3, representing a significant increase in the PRI (+) group (p < 0.001). CONCLUSIONS: The postoperative length of hospital stay is longer and the postoperative medical expenditure is higher for patients with a PRI than for those without a PRI.

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.

Successful perioperative infection control measures after gastroenterological surgery reduced the number of cases of methicillin-resistant Staphylococcus aureus or Clostridioides (Clostridium) difficile infection to almost zero over a 30-year period: a single-department experience.

PURPOSE: To investigate changes in the incidence of postoperative infections in the surgical department of a teaching hospital. METHODS: During the 30-year period from September 1987 to August 2017, 11,568 gastroenterological surgical procedures were performed in our surgical department. This 30-year period was divided into seven periods (A-G), ranging from 2 to 7 years each and based on the infection control methods used in each period. We then compared the rates of incisional surgical site infection (SSI) and organ/space SSI; remote infection (RI) including respiratory tract infection (RTI), intravascular catheter-related infection, and urinary tract infection (UTI); and antibiotic-associated colitis caused by methicillin-resistant Staphylococcus aureus (MRSA) enteritis or Clostridioides (Clostridium) difficile-associated disease (CDAD) among the seven periods. RESULTS: In periods B (September 1990-August 1997) and E (November 2004-July 2007), when a unique antibiotic therapy devised in our department was in use, MRSA was isolated from only 0.3% and 0.4% of surgical patients, respectively, and these rates were significantly lower than those in the other periods (p < 0.05). The rate of CDAD increased during period F (August 2007-July 2014), but in period G (August 2014-August 2017), restrictions were placed on the use of antibiotics with a strong anti-anaerobic action and, in this period, the rate of CDAD was only 0.04%, which was significantly lower than that in period F (p < 0.05). CONCLUSIONS: Limiting the use of antibiotics that tend to disrupt the intestinal flora may reduce the rates of MRSA infection and CDAD after gastroenterological surgery.

Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan.

We assessed the efficacy and safety of fidaxomicin, a narrow-spectrum macrocyclic antibiotic, for treating inpatients with Clostridioides (Clostridium) difficile infection (CDI) in Japan. The objective was to demonstrate the non-inferior efficacy of fidaxomicin versus vancomycin. This Phase III, vancomycin-controlled, double-blind, parallel-group study enrolled adults with CDI. Patients were randomly assigned to receive fidaxomicin (200 mg twice daily, orally) or vancomycin (125 mg four-times daily, orally) for 10 days. The primary endpoint was global cure rate of CDI (proportion of patients cured at end of treatment with no recurrence during 28-day follow-up). Non-inferiority margin of 10% was pre-specified. Two-hundred and twelve patients were randomized and received treatment at 82 hospitals. Global cure rate was 67.3% (70/104) with fidaxomicin and 65.7% (71/108) with vancomycin: difference 1.2% [95% confidence interval (CI) -11.3-13.7]. Non-inferiority was not demonstrated. Post-hoc analysis in full analysis set patients who received at least 3 days' treatment revealed a higher global cure rate for fidaxomicin [70/97 (72.2%)] than vancomycin [71/106 (67.0%)]: difference 4.6% (95% CI -7.9-17.1). Recurrence rate in the full analysis set for recurrence was lower in fidaxomicin- [17/87 (19.5%)] than vancomycin-treated [24/95 (25.3%)] patients. Adverse event incidences and profiles were similar for both treatments. Though non-inferiority was not demonstrated for fidaxomicin versus vancomycin, global cure rate was numerically higher and recurrence rate lower for fidaxomicin than vancomycin. Fidaxomicin could be an option for the treatment of CDI in an era of reduced antibiotic susceptibility, and to reduce the incidence of recurrence in Japanese patients. CLINICALTRIALS. GOV IDENTIFIER: NCT02179658.

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.

[A Case of Advanced Gastric Cancer with Ptosis Caused by Orbital Metastasis].

Orbital metastasis of gastric cancer occurs very rarely.A 76-year-old woman, who consulted another doctor with the chief complaints of palpitation, shortness of breath, and anorexia 1 month previously, was referred to our clinic for workup and treatment.Workup revealed type III advanced gastric cancer at the lesser curvature of the gastric antrum.Biopsy revealed a diagnosis of poorly differentiated adenocarcinoma.As computed tomography suggested periaortic lymph node metastasis, a diagnosis of T4a(SE)N3aM1(LYM), cStage IV was made.Two weeks later, ptosis was observed in the right eye, and positron emission tomography-computed tomography(PET-CT)revealed metastasis to the right superior rectus muscle.No intracranial tumor progression was observed.The Cyberknife system(20 Gy/1 Fr)was used for treating the orbital tumor. Increased LYM was observed even after 2 courses of S-1 plus oxaliplatin(SOX)therapy.Therefore, weekly combination therapy of paclitaxel and ramucirumab(wPTX plus Rmab)was administered as second-line therapy.No new distal metastasis has been detected in the 10 months since the orbital metastasis development, and the patient is still alive.

[Carcinosarcoma of the Esophagus That Presented as Esophageal Stenosis].

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.

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.

Neutrophil/lymphocyte ratio has a prognostic value for patients with terminal cancer.

BACKGROUND: Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex. In this study, we evaluated the feasibility of neutrophil/lymphocyte ratio (NLR) as an index to estimate survival in terminal cancer patients. METHODS: NLR was calculated retrospectively based on blood tests performed at 3 months, 2 months, 4 weeks, 3 weeks, 2 weeks, 1 week, and within 3 days before death in 160 cancer patients (82 men, 78 women; age range, 33-99 years; mean age, 69.8 years). RESULTS: NLR increased significantly with time (P < 0.0001). Mean NLR was significantly higher in patients who died within 4 weeks (29.82) than in those who lived more than 4 weeks (6.15). The NLR cutoff point was set at 9.21 according to receiver operating characteristic curve analysis (area under the curve, 0.82; 95% confidence interval, 0.79-0.85). We inferred that life expectancy would be <4 weeks when NLR >9.21. The sensitivity, specificity, positive predictive value, and negative predictive value were 65.6, 84.1, 90.6, and 51.1%, respectively. The positive and negative likelihood ratios were 4.125 and 0.409, respectively. CONCLUSIONS: NLR appears to be a useful and simple parameter to predict the clinical outcomes of patients with terminal cancer.

Open surgery versus laparoscopic surgery after stent insertion for obstructive colorectal cancer.

PURPOSE: To compare the outcomes of laparoscopic surgery vs. open surgery after insertion of a colonic stent for obstructive colorectal cancer. METHODS: Between April 2005 and August 2013, 58 patients underwent surgery after the insertion of a colonic stent for obstructive colorectal cancer. We analyzed the outcomes of the patients who underwent laparoscopic surgery vs. those who underwent open surgery. RESULTS: We compared blood loss, operative time, hospital stay, and complications in 26 patients who underwent laparoscopic surgery and 32 patients who underwent open surgery. Blood loss was significantly less in the laparoscopic surgery group, but operative time was significantly shorter in the open surgery group. The length of hospital stay was shorter in the laparoscopic surgery group than in the open surgery group, but the difference was not significant. There was no significant difference in postoperative surgical complications between the groups. CONCLUSION: The patients who underwent laparoscopic resection had less blood loss, although no significant difference was found in postoperative morbidity or mortality. Thus, laparoscopic resection after stent insertion is a feasible and safe option for patients with obstructive colorectal cancer.

[SURVEILLANCE OF PERIOPERATIVE INFECTIONS AND INFECTION CONTROL].

Postoperative infections are classified into surgical site infections and remote infections. The risk factors associated with postoperative infections are related to medical practice, the patient, and bacteria. Postoperative infections not only prolong hospitalizations and increase patient burden but also affect prognosis. It is therefore important to conduct surveillance of postoperative complications at each facility to elucidate the risk factors for infection and to implement and evaluate infection control measures. Moreover, with the aging of the population, more surgeries are being performed in elderly individuals. However, the elderly tend to have age-related declines in the function of major organs as well as comorbidities, and surgeries in them carry a high risk despite advances in operative techniques and perioperative management. It is therefore important to determine surgical indications carefully by sufficiently assessing the risk preoperatively and performing appropriate perioperative management.

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.

Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011.

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of ß-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

Successful treatment of a common hepatic artery pseudoaneurysm using a coronary covered stent following pancreatoduodenectomy: report of a case.

This report presents the case of a common hepatic artery (CHA) pseudoaneurysm secondary to postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), which was successfully treated using a coronary covered stent. A 70-year-old female underwent subtotal stomach-preserving PD for middle cholangiocarcinoma. POPF was identified on postoperative day (POD) 7, and the patient suddenly lost 500 ml of blood via the abdominal drain on POD 19. Urgent celiac arteriography revealed a CHA pseudoaneurysm. A coronary covered stent was placed to prevent rupture of the pseudoaneurysm and to maintain hepatic arterial flow, instead of performing transarterial embolization. No vascular adverse events were encountered during or after the procedure. Computed tomography and angiography showed a patent stent graft and good hepatic arterial flow 9 months after placement of the stent. Endovascular stent-graft placement not only treated the pseudoaneurysm, but also preserved the arterial blood flow. This report describes the placement of a covered stent graft for delayed hemorrhage after PD.

Risk factors for conversion of laparoscopic cholecystectomy to open surgery associated with the severity characteristics according to the Tokyo guidelines.

PURPOSE: The aim of this retrospective study was to identify the risk factors associated with the severity characteristics in the Tokyo guidelines for conversion to open surgery in patients with acute cholecystitis (AC) who underwent laparoscopic cholecystectomy. METHODS: A total of 225 patients were enrolled in the study. The patients were classified into two groups: a conversion group and a no-conversion group. The preoperative characteristics and therapeutic strategy were analyzed as risk factors for conversion to open surgery. The postoperative outcomes were also analyzed. RESULTS: Conversion to open surgery occurred in 29 patients (12.9%), including seven patients (6.7%) with mild AC and 22 patients (18.5%) with moderate AC. A univariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h, an elevated C-reactive protein (CRP) value and the Tokyo guidelines 2013 (TG 13) severity classification. The multivariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h and a CRP value >11.5 mg/dl. CONCLUSIONS: A duration of symptoms longer than 72 h, which is included in the criterion for moderate AC severity in the TG 13, was an independent risk factor for conversion to open surgery. In addition, adoption of a high CRP value as an additional criterion for moderate AC may increase the utility of the TG 13.

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections.

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.