Sequential multidetector computed tomography assessments after venous graft treatment solution in coronary artery bypass grafting.

OBJECTIVES: To assess the effect of DuraGraft (Somahlution Inc, Jupiter, Fla), an intraoperative graft treatment, on saphenous vein grafts in patients undergoing isolated coronary artery bypass grafting. METHODS: Within patients, 2 saphenous vein grafts were randomized to DuraGraft or heparinized saline. Multidetector computed tomography angiography at 1, 3, and 12 months assessed change in wall thickness (primary end point at 3 months), lumen diameter, and maximum narrowing for the whole graft and the proximal 5-cm segment. Safety end points included graft occlusion, death, myocardial infarction, and repeat revascularization. RESULTS: At 3 months, no significant changes were observed between DuraGraft- and saline-treated grafts (125 each) for wall thickness, lumen diameter, and maximum narrowing. At 12 months, DuraGraft-treated grafts demonstrated smaller mean wall thickness, overall (0.12 ± 0.06 vs 0.20 ± 0.31 mm; P = .02) and in the proximal segment (0.11 ± 0.03 vs 0.21 ± 0.33 mm; P = .01). Changes in wall thickness were greater in the proximal segment of saline-treated grafts (0.09 ± 0.29 vs 0.00 ± 0.03 mm; P = .04). Increase in maximum graft narrowing was larger in the proximal segment in the saline-treated grafts (4.7% ± 12.7% vs 0.2% ± 3.8%; P = .01). Nine DuraGraft and 11 saline grafts had occluded or thrombosed. One myocardial infarction was associated with a saline graft occlusion. No deaths or revascularizations were observed. CONCLUSIONS: DuraGraft demonstrated a favorable effect on wall thickness at 12 months, particularly in the proximal segment. Longer-term follow-up in larger studies is needed to evaluate the effect on clinical outcomes.

A novel endothelial damage inhibitor for the treatment of vascular conduits in coronary artery bypass grafting: protocol and rationale for the European, multicentre, prospective, observational DuraGraft registry.

BACKGROUND: Vein graft disease (VGD) impairs graft patency rates and long-term outcomes after coronary artery bypass grafting (CABG). DuraGraft is a novel endothelial-damage inhibitor developed to efficiently protect the structural and functional integrity of the vascular endothelium. The DuraGraft registry will evaluate the long-term clinical outcomes of DuraGraft in patients undergoing CABG procedures. METHODS: This ongoing multicentre, prospective observational registry will enrol 3000 patients undergoing an isolated CABG procedure or a combined procedure (ie, CABG plus valve surgery or other surgery) with at least one saphenous vein grafts or one free arterial graft (ie, radial artery or mammary artery). If a patient is enrolled, all free grafts (SVG and arterial will be treated with DuraGraft. Data on baseline, clinical, and angiographic characteristics as well as procedural and clinical events will be collected. The primary outcome measure is the occurrence of a major adverse cardiac event (MACE; defined as death, non-fatal myocardial-infarction, or need for repeat-revascularisation). Secondary outcome measures are the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as death, non-fatal myocardial-infarction, repeat-revascularisation, or stroke), patient-reported quality of life, and health-economic data. Patient assessments will be performed during hospitalisation, at 1-month, 1-year, and annually thereafter to 5 years post-CABG. Events will be adjudicated by an independent clinical events committee. This European, multi-institutional registry will provide detailed insights into clinical outcome associated with DuraGraft. DISCUSSION: This European, multi-institutional registry will provide detailed insights into clinical outcome associated with the use of DuraGraft. Beyond that, and given the comprehensive data sets comprising of patient, procedural, and graft parameters that are being collected, the registry will enable for multiple subgroup analyses targeting focus groups or specific clinical questions. These may include analysis of subpopulations such as patients with diabetes or multimorbid high-risk patients (patient level), evaluation of relevance of harvesting technique including endoscopic versus open conduit harvesting (procedural level), or particular graft-specific aspects (conduit level). TRIAL REGISTRATION: ClinicalTrials.gov NCT02922088 . Registered October 3, 2016. ETHICS AND DISSEMINATION: The regional ethics committees have approved the registry. Results will be submitted for publication.

DuraGraft vascular conduit preservation solution in patients undergoing coronary artery bypass grafting: rationale and design of a within-patient randomised multicentre trial.

Introduction: Saphenous vein grafts (SVGs) remain the most often used conduits in coronary artery bypass grafting (CABG). However, they are prone to vein graft disease (VGD) during follow-up, which may compromise clinical outcomes. Injury to the SVG endothelium during harvesting and storage promotes neointimal hyperplasia that can advance to atherosclerosis characterised by SVG failure. This trial investigates the potential benefit of DuraGraft, a novel, one-time intraoperative graft treatment developed to efficiently protect the structural and functional integrity of the vascular endothelium, on the development and progression of VGD in CABG patients. Methods and analysis: This ongoing prospective randomised, double-blinded multicentre trial (NCT02272582/NCT02774824) includes patients undergoing isolated CABG requiring at least two SVGs. It compares the impact of DuraGraft, a novel treatment against VGD versus the standard-of-care (SOC; heparinised saline) using a within-patient randomisation (with one SVG treated with DuraGraft and the other treated with SOC). Besides clinical assessments, patients undergo longitudinal 64-slice or better multidetector CT (MDCT) angiography of paired grafts (within each patient) at 4-6 weeks, 3 months and 12 months. Primary endpoints will be the magnitude of change in mean wall thickness and lumen diameter (stenosis) of paired grafts, at 3 and 12 months, respectively. Besides the evaluation of overall safety, longitudinal assessment of each graft (secondary endpoint) is performed in order to obtain insight into graft behaviour after CABG. Enrolment of 119 patients was successfully completed, and analysis of MDCT angiography follow-up is ongoing with the completed analysis becoming available by end of first quarter of 2018. Ethics and dissemination: The regional ethics committees have approved the trial. Results will be submitted for publication. Clinical trial identifier: NCT02272582 and NCT02774824.

In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends).

OBJECTIVES: SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing study to monitor worldwide antimicrobial resistance trends among aerobic and facultatively anaerobic Gram-negative bacilli (GNB) isolated from intra-abdominal infections. This 2004 report summarizes the most recently completed annual data from SMART. METHODS: During 2004, 81 medical centres from 28 countries in five global regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 6156 unique aerobic and facultatively anaerobic GNB were isolated from intra-abdominal infections. Enterobacteriaceae composed 86% of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most consistently active against the Enterobacteriaceae. Escherichia coli was the most commonly isolated species (48%), and the susceptibility rate to the quinolones was lowest in Asia/Pacific and Latin America. Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 10% of E. coli, 17% of Klebsiella spp. and 22% of Enterobacter spp. worldwide, representing a slight increase over the two previous years. ESBL producers typically had a more antibiotic-resistant profile than non-ESBL producers but were usually susceptible to the carbapenems. CONCLUSIONS: Antimicrobial resistance among GNB isolated from intra-abdominal infections continued to be a problem worldwide in 2004, with the highest rates of resistance overall in the Asia/Pacific region. The carbapenems and amikacin were the most consistently active agents in vitro against Enterobacteriaceae isolated from intra-abdominal infections worldwide.

In vitro susceptibilities of Escherichia coli isolated from patients with intra-abdominal infections worldwide in 2002-2004: results from SMART (Study for Monitoring Antimicrobial Resistance Trends).

BACKGROUND: Since 2002, the worldwide Study for Monitoring Antimicrobial Resistance Trends (SMART) has tracked resistance patterns among aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections. Escherichia coli has been by far the most frequently isolated species. METHODS: Antimicrobial susceptibilities for consecutive non-duplicate isolates of aerobic and facultative gram-negative bacilli recovered from intra-abdominal infections were determined by standard broth microdilution techniques. A subanalysis was performed for E. coli isolates from the first three years of the study. RESULTS: A total of 7,002 E. coli isolates were recovered, most commonly from the peritoneal cavity followed by the biliary tract. Susceptibility rates to the 12 antimicrobial agents tested differed among geographic regions, with isolates from Asia/Pacific generally having the highest resistance rates. Overall, extended-spectrum beta-lactamase (ESBL)-producers had a more antibiotic-resistant profile than non-ESBL-producers but usually were susceptible to the carbapenems and amikacin. Community-acquired E. coli strains comprised slightly more than one-half of the isolates and were susceptible to the agents tested more frequently than were hospital-acquired E. coli. CONCLUSIONS: The prevalence of antimicrobial resistance among E. coli isolated from intraabdominal infections is not inconsequential, especially in the Asia/Pacific region. The carbapenems and amikacin were consistently active in vitro against E. coli isolates worldwide, including ESBL-producers.

Acquisition of resistant bowel flora during a double-blind randomized clinical trial of ertapenem versus piperacillin-tazobactam therapy for intraabdominal infections.

Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of Enterobacteriaceae resistant to the study drug, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella species, Pseudomonas aeruginosa resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant Enterococcus faecalis or Enterococcus faecium. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points. Enterobacteriaceae resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (P = 0.007). Neither ESBL-producing E. coli or Klebsiella species nor P. aeruginosa resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant P. aeruginosa was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (P = 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%; P = 0.10). In this study, the acquisition of resistant Enterobacteriaceae occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.

In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART).

OBJECTIVES: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance programme was begun in 2002 to monitor antimicrobial resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections worldwide. METHODS: In 2003, 74 medical centres from 23 countries collected isolates for testing. Antimicrobial susceptibility testing was performed using broth microdilution according to the NCCLS guidelines for MIC testing. RESULTS: A total of 5658 aerobic and facultative GNB were isolated from intra-abdominal infections. Enterobacteriaceae composed 84% of the total isolates. Among the agents tested, the carbapenems were the most consistently active against the Enterobacteriaceae. E. coli was the most common isolate (46%), and the susceptibility rate to the quinolone (70-90% susceptible), cephalosporin (80-97% susceptible), aminoglycoside (77-100% susceptible) and carbapenem (99-100% susceptible) agents tested varied among geographic regions, with isolates from the Asia/Pacific region generally being the most resistant. Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 9% of E. coli, 14% of Klebsiella spp., and 14% of Enterobacter spp. worldwide. ESBL producers generally had a more antibiotic-resistant profile than non-ESBL producers. CONCLUSIONS: Antimicrobial resistance among GNB isolated from intra-abdominal infections is a problem worldwide, especially in the Asia/Pacific region. The carbapenems ertapenem, meropenem and imipenem are highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including organisms that produce ESBLs.

In vitro susceptibilities of aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2002 Study for Monitoring Antimicrobial Resistance Trends (SMART).

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) was begun in 2002 to monitor international drug-resistance patterns among aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections. METHODS: In 2002, 40 medical centers from 17 countries collected consecutive non-duplicate isolates from intra-abdominal infections for susceptibility testing against 12 antimicrobial agents using the broth microdilution methods recommended by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). RESULTS: A total of 3,134 aerobic and facultative gram-negative bacilli were isolated. Enterobacteriaceae accounted for 82% of the total and were most consistently susceptible to amikacin and the carbapenems. Escherichia coli (45%) and Klebsiella spp. (17%) were the most common species. The susceptibility rates of these organisms to the 12 antimicrobial agents differed among geographic regions, with isolates from the Asia/Pacific and Latin American regions usually having the highest rates of resistance. Ampicillin/sulbactam was the agent least frequently active against E. coli (56% susceptible) and Klebsiella spp. (73% susceptible). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 7% of E. coli, 13% of Klebsiella spp., and 18% of Enterobacter spp. Producers of ESBL overall had a more antibiotic-resistant profile than non-producers but were usually susceptible to carbapenems. CONCLUSIONS: Antimicrobial resistance rates among gram-negative bacilli isolated from intra-abdominal infections differed among geographic regions. The carbapenems were consistently active in vitro against Enterobacteriaceae worldwide, including ESBL producers.

Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial.

OBJECTIVE: To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection. SUMMARY BACKGROUND DATA: Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections. METHODS This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections. RESULTS: Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam. CONCLUSIONS: In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.