Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Large Contaminated Ventral Hernia Repair Using Component Separation Technique with Synthetic Mesh.

BACKGROUND: Large ventral hernia repair represents a major reconstructive surgical challenge, especially under contaminated conditions. Synthetic mesh is usually avoided in these circumstances because of fear of mesh infection, although evidence is outdated and does not regard new materials and techniques. The authors evaluated the safety of synthetic mesh in large contaminated ventral hernia repair. METHODS: All large ventral hernias repaired with the components separation technique and polypropylene mesh were included in analysis. Primary outcomes were wound and medical complications, with a focus on surgical-site infection and mesh removal. For risk analysis, patients were stratified by surgical wound class, Ventral Hernia Working Group grade, and modified Ventral Hernia Working Group grade. RESULTS: One hundred thirty-seven patients were included, with a mean age of 58.6 years, mean body mass index of 26.6 cm2, and mean defect size of 235.6 cm2. Surgical-site infection and total wound complication rates were 16.1 and 48.9 percent, respectively. The surgical wound class distribution of surgical-site infections was as follows: clean, five of 56 (9.1 percent); clean-contaminated, five of 34 (14.7 percent); contaminated, three of 19 (15.8 percent); and dirty/infected, nine of 28 (32.1 percent). Seven meshes (5.1 percent) needed removal, two after clean repairs, three after clean-contaminated repairs, and two after dirty/infected repairs. Surgical wound class (OR, 1.77; 95 percent CI, 1.20 to 2.61) and Ventral Hernia Working Group grade (OR, 2.31; 95 percent CI, 1.24 to 4.28) were predictors of surgical-site infection. CONCLUSION: Rate of surgical-site infection after large contaminated ventral hernia repair with synthetic mesh is considerable but with a low mesh removal rate.

Efficacy and Safety of Ultrapure Alginate-Based Anti-Adhesion Gel in Experimental Peritonitis.

BACKGROUND: Intra-abdominal infection may lead to adhesion and abscess formation. An adhesion barrier can reduce these complications but also aggravate intra-peritoneal infection, causing the opposite effects. The fear of infection propagation has limited clinical adhesion barrier use in a contaminated or infected abdomen. This study evaluated both adhesion and abscess reduction and infection propagation of a new ultrapure alginate-based anti-adhesive barrier gel in a rat peritonitis model. METHODS: In 64 male Wistar rats, bacterial peritonitis was induced via intra-abdominal injection of a mixture of sterile feces, 10(5) colony-forming units (CFU) of Escherichia coli, and 10(4) CFU of Bacteroides fragilis. Surgical debridement and peritoneal lavage were performed 1 h after inoculation. Animals were randomly allocated in equal numbers to a control group or an alginate gel group. Animals were sacrificed on day five post-operatively. Death and the presence and size of intra-abdominal abscesses were noted, and adhesions were scored. All outcomes were compared in the two groups. RESULTS: Seventeen rats (27%) died prematurely without any difference between the groups. Of the surviving rats in the alginate gel group, 88% developed abscesses vs. 100% of the control group. There was no significant difference in the abscess scores or incidence rates of adhesion formation between the groups. The adhesion scores were lower for the alginate gel group compared with control animals (p=0.04). CONCLUSION: Ultrapure alginate gel reduces adhesion severity but not abscesses. The gel seemed to be safe, not aggravating intra-peritoneal infection in this abdominal infection model.

Surgical techniques for parastomal hernia repair: a systematic review of the literature.

BACKGROUND: Parastomal hernias are a frequent complication of enterostomies that require surgical treatment in approximately half of patients. This systematic review aimed to evaluate and compare the safety and effectiveness of the surgical techniques available for parastomal hernia repair. METHODS: Systematic review was performed in accordance with PRISMA. Assessment of methodological quality and selection of studies of parastomal hernia repair was done with a modified MINORS. Subgroups were formed for each surgical technique. Primary outcome was recurrence after at least 1-year follow-up. Secondary outcomes were mortality and postoperative morbidity. Outcomes were analyzed using weighted pooled proportions and logistic regression. RESULTS: Thirty studies were included with the majority retrospective. Suture repair resulted in a significantly increased recurrence rate when compared with mesh repair (odds ratio [OR] 8.9, 95% confidence interval [CI] 5.2-15.1; P < 0.0001). Recurrence rates for mesh repair ranged from 6.9% to 17% and did not differ significantly. In the laparoscopic repair group, the Sugarbaker technique had less recurrences than the keyhole technique (OR 2.3, 95% CI 1.2-4.6; P = 0.016). Morbidity did not differ between techniques. The overall rate of mesh infections was low (3%, 95% CI 2) and comparable for each type of mesh repair. CONCLUSIONS: Suture repair of parastomal hernia should be abandoned because of increased recurrence rates. The use of mesh in parastomal hernia repair significantly reduces recurrence rates and is safe with a low overall rate of mesh infection. In laparoscopic repair, the Sugarbaker technique is superior over the keyhole technique showing fewer recurrences.

Repair of parastomal hernias with biologic grafts: a systematic review.

BACKGROUND: Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias. METHODS: Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms 'paracolostomy', 'paraileostomy', 'parastomal', 'colostomy', 'ileostomy', 'hernia', 'defect', 'closure', 'repair' and 'reconstruction' were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity. RESULTS: Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8-25.9) of patients and wound-related complications in 26.2% (95% CI 14.7-39.5). No mortality or graft infections were reported. CONCLUSIONS: The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts.

Peritoneal cytokines predict mortality after surgical treatment of secondary peritonitis in the rat.

BACKGROUND: The study aimed to analyze if peritoneal cytokine levels can predict survival in an experimental model for peritonitis. Early identification of patients most at risk for adverse outcomes would facilitate the decision for aggressive therapy in order to maximally exploit their chance for survival. STUDY DESIGN: Peritonitis was induced by intraperitoneal injection of a feces/bacteria mixture in 175 rats. Surgical debridement was performed after 1 hour. Abdominal fluid samples were taken after 24 and 72 hours for the measurement of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. Surviving animals were sacrificed after 5 days and correlations between cytokine levels and survival were analyzed. RESULTS: Altogether, 60 animals died prematurely, 12 before the first sampling of cytokines. So, 48 nonsurvivors and 115 survivors were analyzed. Peritoneal cytokine levels were much higher (p < 0.0001) in nonsurvivors than in survivors. At 24 hours there were strong correlations between cytokine levels, especially between IL-6 and IL-10 (r = 0.93). Peritoneal cytokines at 24 hours also discriminated between animals dying within the next 24 hours and those dying later. A strongly (p < 0.0001) increased mortality was observed if IL-6, IL-10, or TNF-alpha levels exceeded 2, 1, or 0.2 ng/mL, respectively. Receiver operating characteristic curves were promising for all 3, but IL-10 showed the best characteristics, with an area under the curve of 0.94 and 67% sensitivity at 95% specificity, obtained at a cut-off value of 1.26 ng/mL. CONCLUSIONS: These data should generate renewed interest to examine the peritoneal cytokines as early markers for adverse outcomes in patients with secondary peritonitis. Possibly, combinations of peritoneal cytokines with other markers can lead to much needed, reliable early prediction of disease severity.

Timing and dose of tissue plasminogen activator to prevent abscess formation after surgical treatment of secondary peritonitis in the rat.

Early administration of fibrinolytics after surgical treatment of peritonitis in the rat reduces abscess formation. The current study investigates the effect of various treatment protocols using intraperitoneal recombinant tissue plasminogen activator (rtPA). Peritonitis was induced in rats and surgical debridement was performed after 1 hour. Animals were treated with rtPA at different time points. Abdominal fluid samples were taken at 24, 72, and 120 hours for cytokine measurements and cell counts. After 5 days the abdomen was inspected for abscesses. Early administration of rtPA significantly reduced the number of rats with abscesses and the abscess load per rat. Delayed treatment significantly reduced abscess load but not the incidence of abscesses. No meaningful differences in the local inflammatory response were found. rtPA was most effective when applied early and continued for 72 hours, although mortality increased after prolonged treatment. rtPA consistently reduces intra-abdominal abscess formation, and a clinical study seems warranted.

Tissue-type plasminogen activator prevents abscess formation but does not affect healing of bowel anastomoses and laparotomy wounds in rats with secondary peritonitis.

BACKGROUND: Intra-abdominal application of recombinant tissue-type plasminogen activator (rtPA) can decrease the rate of abscess formation in a rat peritonitis model. Before using rtPA clinically, its effects on healing of bowel anastomoses and laparotomy wounds should be investigated. METHODS: Peritonitis was induced in 148 male Wistar rats via intra-abdominal injection of a feces/bacteria mixture. Laparotomy, operative debridement and construction of a colo-colostomy after a limited colectomy or ileo-ileostomy after a limited ileal resection were performed after 1 hour. All animals received antibiotics (ceftriaxone plus metronidazole). In addition to untreated controls, other animals received rtPA in 1 of 3 dosing schemes, starting immediately after operation or 24 hour afterwards. Wound strength and hydroxyproline content of the wound were analyzed after 3 or 7 days. RESULTS: Mortality was 2% and manifestations of excessive bleeding were virtually absent. RtPA significantly decreased the rate of abscess formation. Neither bursting pressure nor breaking strength of the anastomoses was affected by any of the rtPA protocols. The same was true for wound strength in the abdominal fascia. Additionally, wound hydroxyproline content and architecture remained unchanged after rtPA administration. CONCLUSION: Intraperitoneal rtPA administration consistently and significantly decreased the rate of abscess formation, but did not affect wound healing. Clinical studies investigating its potential as an adjunct in the treatment of secondary peritonitis may be warranted.

Tissue-type plasminogen activator prevents formation of intra-abdominal abscesses after surgical treatment of secondary peritonitis in a rat model.

BACKGROUND: Optimal therapy of secondary peritonitis frequently results in the formation of residual abscesses, which bear a substantial mortality and morbidity. This study aims to prove that fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) can reduce abscess formation after surgical treatment of secondary peritonitis in a rat model, without causing unwanted side effects. MATERIALS AND METHODS: Male Wistar rats received an intra-abdominal injection with a suspension of sterile feces, 10(5) cfu Escherichia coli and 10(4) cfu Bacteroides fragilis. Surgical debridement was performed 1 h after inoculation. Animals were randomized into four groups (n = 14 each). Three groups received human rtPA at 1 h (rtPA1); 1 h and 6 h (rtPA2); and 1, 6, and 24 h (rtPA3), respectively. Each dose contained 1.25 mg rtPA. Controls received saline only. Animals were killed after 5 days. RESULTS: rtPA treatment reduced abscess formation in surviving animals, depending on number of doses given. Animals in group rtPA3 had no abscesses in contrast to 88% of the controls (mean 3.6 +/- 2.7 abscesses per rat; p < 0.05). In the rtPA1 and rtPA2 group, frequency of abscess formation was 58 and 33%, respectively. Mortality, course of body weight, and bacteremia were not affected by rtPA and neither were peritoneal cell counts and levels of TNF-alpha, IL-1beta, IL-6 and IL-10. No bleeding complications were observed. CONCLUSION: rtPA reduces intra-abdominal abscess formation after surgical treatment of generalized peritonitis without increasing mortality or affecting the local inflammatory response.

A peritonitis model with low mortality and persisting intra-abdominal abscesses.

Intra-abdominal abscesses are a potential source of recurrent or residual infection after surgical intervention for secondary peritonitis. The development of therapies requires a model which combines low mortality with the formation of persisting abscesses and which is also suitable to study the local inflammatory response. Male Wistar rats were injected intraperitoneally with a mixture of sterile rat faeces, increasing doses of E. coli (10(4)-10(8) cfu/ml) and a fixed dose of B. Fragilis (10(4) cfu/ml). After one h a laparotomy was performed and the peritoneal cavity was debrided. Blood samples were taken under anaesthesia after 6 and 24 h. Abdominal fluid samples were collected (by laparotomy) after 24 and 72 h. The rats were killed after 5 days and the abdomen was inspected for abscesses. Mortality was 90% in the two groups with the highest doses of E. coli and 30% in those with the two lowest doses. In the latter groups all surviving rats but one showed intraabdominal abscesses and bacteremia was encountered frequently, especially after 24 h in the 10(5) cfu E. coli group. The groups receiving 10(4)-10(6) cfu E. coli showed similar plasma IL-6 concentrations after 6 h which were lowered significantly after 24 h. No circulating TNF-alpha was found. Considerable concentrations of TNF-alpha, IL-6, IL-1beta, and IL-10, were found in the peritoneal fluid after 24 h but no differences were observed between the contro groups and those receiving 10(4)-10(6) cfu E. coli. At 72 h cytokine levels were reduced significantly and remained the highest in the animals dosed with 10(6) cfu E. coli. The present model is suitable to study the mechanisms involved in, and prevention of, intra-abdominal abscess formation after surgical treatment of generalized peritonitis.