Oligosaccharides from Polygonatum Cyrtonema Hua: Structural characterization and treatment of LPS-induced peritonitis in mice.

Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) for the first time. Structure characterized using FT-IR, MALDI-TOF-MS, NMR, AFM, and TEM, indicated that PFOS was graminan-type fructan with a degree of polymerization ranging from 5 to 10. A murine model of lipopolysaccharide (LPS)-induced peritonitis was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of PFOS. The result shown that pretreatment with PFOS (1.0 mg/mL) in peritonitis-induced mice could significantly inhibit the level of pro-inflammatory cytokines (TNF-α, IL-1ß) in serum (P < 0.001), increase mice survival rate from 12.5 % to 54 % (P < 0.05), and alleviated lung injury through ameliorating the damage of the pulmonary cellular architecture and reducing inflammatory monocyte accumulation in lung tissue. This effect of oligosaccharides could explain the traditional usage of P. cyrtonema as a tonic medicine for respiratory problems and it could be used as a potential natural ingredient with anti-inflammatory activity.

Evaluating the best empirical antibiotic therapy in patients with acute-on-chronic liver failure and spontaneous bacterial peritonitis.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of advanced cirrhosis. By studying the susceptibility of isolated organisms and analyzing empirical antibiotic therapy combined with clinical outcomes, we aimed to find an improved empirical antibiotic therapy by considering the individual acute-on-chronic liver failure (ACLF) grade for patients with or without sepsis. METHODS: Clinical outcomes of 182 patients were assessed retrospectively with multivariable regression analysis. Each of the 223 isolates was individually evaluated regarding susceptibility results and intrinsic resistances. RESULTS: Piperacillin/tazobactam had the highest antimicrobial susceptibility among monotherapies/fixed combinations, which was significantly lower than combination therapies such as meropenem-linezolid (75.3% vs. 98.5%, P < 0.001). The sensitivity of pathogens to empirical antibiotic therapy correlated with significantly lower inpatient mortality (18.9% vs. 37.0%, P = 0.018), shorter inpatient stay (16.3 ±â€¯10.2 vs. 26.4 ±â€¯21.0 days, P = 0.053) and shorter intensive care treatment (2.1 ±â€¯4.5 vs. 7.9 ±â€¯15.4 days, P = 0.016). The largest difference of mortality was observed in patients with ACLF grade 3 (54.5% vs. 73.1% [sensitive vs. non-sensitive]). CONCLUSION: All SBP patients benefited from efficient empirical antibiotic therapy, regarding the reduced inpatient mortality and complications. For SBP patients with ACLF grade 3 without sepsis, the combination therapy with meropenem-linezolid may be suitable considering the susceptibility results and the concentration in the peritoneal cavity.

Icodextrin Is Associated with a Lower Mortality Rate in Peritoneal Dialysis Patients.

Background:Icodextrin (ICO) improves fluid removal in peritoneal dialysis (PD) patients. However, whether physiological benefits of ICO translate into patient survival remains unclear. We examine the association of ICO and clinical outcomes.Methods:We identified patients who initiated long-term PD from the National Health Insurance Research Database of Taiwan. We matched ICO users with non-users according to propensity score and survival status when ICO was prescribed. We utilized time-dependent analyses to avoid immortal time bias. Additional competing risk models were utilized for the outcomes except for death. The outcomes of interest were time to death, technique failure, peritonitis, major adverse cardiovascular events (MACE), and hospitalization.Results:A total of 4,914 PD patients were enrolled and 2,836 PD patients (57.7%) were identified as ICO users. The ICO users had significantly better overall survival (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 - 0.86), especially among early ICO users (HR 0.64; 95% CI 0.54 - 0.77, p value for interaction: 0.007). The ICO users were associated with higher risk of peritonitis (subdistribution HR 1.22, 95% CI 1.06 - 1.14) and hospitalization (subdistribution HR 1.14, 95% CI 1.05 - 1.24), considering competing risk of death. However, when considering ICO use as a time-varying covariate, ICO users shared similar risks for technique failure, peritonitis, MACE, and hospitalization as non-users. The effect of ICO on mortality was especially prominent among those early users.Conclusions:After adjustments for immortal time biases, ICO users were significantly associated with approximately 20% reduction in mortality, especially among early users.

Tanshinone IIA attenuates sepsis-induced immunosuppression and improves survival rate in a mice peritonitis model.

BACKGROUND: The importance of sepsis-induced immunosuppression and its contribution to mortality has recently emerged. In this study we examined the effects of Tanshinone II-A (TSN), a widely used traditional Chinese medicine, on immunosuppression in experimental peritonitis induced septic mice. MATERIALS AND METHODS: Sepsis was achieved by means of cecal ligation and puncture (CLP). TSN at different doses (5, 15 and 45 mg/kg, i.p.) were used at different time-points (0, 3, 6 and 12 h) after CLP to evaluate its effect on the survival of septic mice. In parallel experiments, mice given TSN at optimal dose and time-point were euthanized to collect peritoneal macrophages, blood and tissue samples at 24 h after the CLP. RESULTS: TSN improved the survival of septic mice in a dose- and time-dependent manner. TSN reduced CLP-induced serum biochemical parameters and protected organs from histopathological injuries. CLP-induced apoptosis and decreased percentages of splenic CD4+ and CD8+ T cells were reversed in TSN-treated mice. Moreover, CLP-induced formation of regulatory T cells (Treg) in the spleen was abolished in TSN-treated mice. CLP greatly decreased the levels of interferon-γ and interleukin (IL)-2 in the spleen, while the levels of IL-4 and IL-10 increased after CLP. TSN completely reversed these alterations and elicited a more-balanced Th1/Th2 response. Moreover, TSN promoted macrophage phagocytotic activity and improved bacterial clearance of septic mice. Lastly, TSN abolished CLP-triggered increase in serum HMBG1 level. And HMGB1 neutralization could increase the percentages of splenic CD3+CD4+/CD3+CD8+ lymphocytes and decreased the Treg population. CONCLUSIONS: Overall, our data suggest that TSN exerts immune modulatory effect and might be a useful strategy to ameliorate immunosuppression in polymicrobial sepsis.

"Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents.

BACKGROUND: Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats. DESIGN: Rats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed. RESULTS: Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats. CONCLUSIONS: Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation.

Microbiology and resistance in first episodes of spontaneous bacterial peritonitis: implications for management and prognosis.

PURPOSE: International guidelines for antibiotic treatment of spontaneous bacterial peritonitis (SBP) are based on studies conducted decades ago and do not reflect regional differences of bacterial epidemiology. METHODS: We retrospectively analyzed epidemiology of agents, antibiotic resistance patterns, and survival in liver cirrhosis patients with their first episode of SBP during the years 2007-2013. RESULTS: Of the 311 patients included, 114 patients had a positive ascites culture, and 197 had an ascitic neutrophil count >250 µL. Gram-positive bacteria (47.8%) were more frequently found than Gram-negatives (44.9%), fungi in 7.2%. Enterobacter spp. (40.6%), Enterococcus spp. (26.1%), and Staphylcoccus spp. (13.8%) were the most frequently isolated agents. Third-generation cephalosporins covered 70.2% of non-nosocomial and 56.3% of nosocomial-acquired SBP cases.When SBP was diagnosed by a positive ascitic culture, survival was highly significantly reduced (mean: 13.9 ± 2.9 months; 95% confidence interval [CI]: 8.1-19.8) compared with culture-negative SBP patients (mean: 44.1 ± 5.4 months; 95% CI: 33.4-54.9; P = 0.000). Along with model of end-stage liver disease score and intensive care unit contact, a positive ascites culture remained an independent risk factor associated with poor survival (odds ratio: 1.49; 95% CI: 1.09-2.03) in multivariate analysis; piperacillin/tazobactam proved to be an adequate antibiotic for nosocomial and non-nosocomial SBP in 85.1% and 92.5%, respectively. SBP infection with Enterococcus spp. was associated with poor patient survival (P = 0.048). CONCLUSIONS: Third-generation cephalosporins have poor microbial coverage for treatment of SBP. Current guidelines need to adapt for the emerging number of Gram-positive infectious agents in SBP patients.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS / EFEITOS DO TRATAMENTO TÓPICO COM O LÁTEX DA EUPHORBIA TIRUCALLI NA SOBREVIDA E NAS ADERÊNCIAS INTESTINAIS DE RATOS COM PERITONITE EXPERIMENTAL

Background: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. Aim: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. Methods: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. Results: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. Conclusions: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Racional: O uso de plantas da família Euphorbiaceae, principalmente a Euphorbia tirucalli (avelós), tem sido popularmente difundido para o tratamento de uma variedade de doenças de natureza infecciosa, tumoral e inflamatória. Objetivo: Avaliar o efeito do tratamento tópico com a solução aquosa do látex do avelós na sobrevida e nas aderências intestinas de ratos com peritonite experimental. Métodos: Foi induzido peritonite em 24 ratos Wistar e randomizados em quatro grupos de seis, assim distribuídos: 1) Controle - (n=6), nenhum tratamento; 2) Antibiótico - (n=6), tratamento com dose única intramuscular de antibiótico Unasyn (Pfizer - São Paulo); 3) Salina - (n=6), lavagem da cavidade abdominal com solução fisiológica 0,9%; 4) E.Tirucalli - (n=6), lavagem da cavidade abdominal com E. tirucalli na concentração de 12 mg/ml. Os animais que morreram foram submetidos à necropsia e o horário do óbito anotado. Os sobreviventes foram submetidos à eutanásia no 11odia de pós-operatório e, posteriormente, realizou-se a necropsia para avaliação da formação de aderências. Resultados: Os grupos controle e antibiótico obtiveram diferença significativa (p<0,01) com relação às horas de vida entre os grupos salina e E. tirucalli. Não houve diferença significativa (p>0,05) na sobrevida dos animais dos grupos salina e E. tirucalli, no entanto, houve um óbito no grupo salina. A necropsia dos animais dos grupos salina e E. tirucalli mostrou aderências firmes e resistentes à manipulação entre alças intestinais e parede abdominal. Os demais grupos não tiveram formação de aderências. Conclusão: O tratamento tópico com o látex da E. tirucalli estimulou maior formação de aderências intestinais e evitou o óbito de todos animais com peritonite até o período avaliado.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS.

BACKGROUND: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. AIM: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. METHODS: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. RESULTS: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. CONCLUSIONS: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Abdominal candidiasis is a hidden reservoir of echinocandin resistance.

FKS mutant Candida isolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin. Candida glabrata (29%) and Candida albicans (14%) mutants were identified. Multidrug-resistant bacteria were recovered from 83% of FKS mutant infections. Mutations were associated with prolonged echinocandin exposure (P = 0.01), breakthrough infections (P = 0.03), and therapeutic failures despite source control interventions (100%). Abdominal candidiasis is a hidden reservoir for the emergence of echinocandin-resistant Candida.

Spontaneous ascitic fluid infection in liver cirrhosis: bacteriological profile and response to antibiotic therapy.

BACKGROUND: Spontaneous ascitic fluid infection (SAI) is common in cirrhotic patients leading to significant morbidity and mortality. Third-generation cephalosporins are currently recommended as first-line therapy. We conducted a prospective study to determine bacterial etiology, susceptibility patterns, and clinical epidemiology including 1-month mortality of SAIs among patients with cirrhosis. METHODS: Records of 600 patients with suspected SAI over a 4-year period were analyzed. Empirical cefotaxime/ceftriaxone was initiated in patients who had a neutrophil count >250/mm(3). Treatment failure was defined by absence of clinical improvement and/or significant decrease in neutrophil count of ascites (<25 % of base line value) by 72 h of therapy. RESULTS: Seventy patients (11.6 %) had SAI, including 40 (57.1 %) culture-negative neutrocytic ascites (CNNA), 25 (35.8 %) spontaneous bacterial peritonitis (SBP), and five (7 %) monomicrobial non-neutrocytic bacterascites (MNB). Gram-negative bacilli (Klebsiella and E. coli) were the commonest organisms. The overall response rate to ceftriaxone was 62.8 % (44/70). Among culture-positive patients (SBP and MNB), sensitivity rates to ceftriaxone was 50 %, while it was 53.3 % for quinolones, 70 % for piperacillin-tazobactam, and 93.3 % for cefoperazone-sulbactam combination. Thirty-day mortality was lower for CNNA compared to SBP (20 % vs. 40 %, p < 0.001) and for patients with response compared to no response to first antibiotic (11.3 % vs. 53.8 %, p < 0.001). CONCLUSION: The response of SAI to third-generation cephalosporins was low at our center. Cefoperazone-sulbactam could be a better alternative choice.

Antibacterial efficacy of temperate phage-mediated inhibition of bacterial group motilities.

Phage therapy against bacterial pathogens has been resurrected as an alternative and supplementary anti-infective modality. Here, we observed that bacterial group motilities were impaired in Pseudomonas aeruginosa strain PA14 lysogens for some temperate siphophages; the PA14 lysogens for DMS3 and MP22 were impaired in swarming motility, whereas the PA14 lysogen for D3112 was impaired in twitching motility. The swarming and twitching motilities of PA14 were also affected in the presence of MP22 and D3112, respectively. The in vitro killing activities of D3112 and MP22 toward PA14 did not differ, and neither did their in vivo persistence in the absence of bacterial infections in mice as well as in flies. Nevertheless, administration of D3112, not MP22, significantly reduced the mortality and the bacterial burdens in murine peritonitis-sepsis and Drosophila systemic infection caused by PA14. Taken together, we suggest that a temperate phage-mediated twitching motility inhibition might be comparably effective to control the acute infections caused by P. aeruginosa.

[Surgical therapy of peritonitis]. / Chirurgische Therapie der Peritonitis.

Despite significant progress the therapy of peritonitis remains challenging. With a mortality of up to 20% peritonitis is a predominant cause of death due to surgical infections. An early and efficient source control combined with effective antibiotic therapy and modern intensive care and sepsis therapy are definitive for the outcome and prognosis of secondary peritonitis. In approximately 90% of patients an effective source control can be achieved by one single operation with extensive peritoneal lavage. A reoperation is necessary in only about 10% of patients. The aggressive concepts of planned relaparotomy or open packing are associated with increased morbidity and are indicated only in rare cases. The gold standard is to attempt a definitive source control by one single operation. An operative revision should be performed only on demand. The antibiotic therapy should begin with a broadly calculated empirical therapy and should later be adapted to microbiological findings. The therapy of sepsis requires standardized and state of the art intensive care.

A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units.

Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005-2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 2 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study.

BACKGROUND/AIMS: Low protein concentration in ascitic fluid has been identified as a risk factor for spontaneous bacterial peritonitis (SBP). Until now, primary prophylaxis has not been recommended in these patients. The aim was to investigate the efficacy of long-term administration of ciprofloxacin to prevent SBP. METHODS: One hundred cirrhotic patients with <1.5 g/dl of total protein in ascitic fluid were randomized prospectively, in a double blind fashion to receive ciprofloxacin 500 mg/day (n=50) or placebo (n=50) for 12 months. RESULTS: Baseline data were similar in both groups. In the ciprofloxacin group, SBP occurred almost four times less frequently than in the placebo group but it was not statistically significant. The probability of survival at 12 months was significantly higher in patients receiving ciprofloxacin (86% versus 66%) (p<0.04). SBP and sepsis were the most frequent causes of death in the placebo group whereas gastrointestinal bleeding was responsible for the most deaths in the ciprofloxacin group. The probability of remaining free of bacterial infections was higher in patients receiving ciprofloxacin (80% versus 55%) (p=0.05). CONCLUSIONS: Patients with cirrhosis and low protein concentration in ascitic fluid are candidates to receive long-term prophylaxis to reduce the risk of infections and improve survival.

Effects of peritoneal lavage with lidocaine on survival of rats with fecal peritonitis.

PURPOSE: To study the effects of peritoneal lavage with a 2% lidocaine solution, on the survival of the rats submitted to peritonitis caused by their own feces. METHODS: Forty-eight Wistar rats, weighting between 300 g and 330 g (mean, 311,45 +/-9,67 g), were submitted to laparotomy 6 hours following induction of fecal peritonitis. Animals were randomly divided into four groups of 12 each as follows: 1- Control, no therapy; 2- Drying of the abdominal cavity; 3- Peritoneal lavage with saline and drying; 4- Peritoneal lavage with a 2% lidocaine solution and drying. Animals that died were submitted to necropsy and the time of their death recorded; survivors were killed on the post-operation 11th day and necropsied. RESULTS: Death occurred within 52 h in all animals of group 1; within 126 h in 100% of those of group 2; within 50 h in 50% of those of group 3. All animals of group 4 survived. Survival on the 11 th day was higher in groups 3 and 4 than in groups 1 and 2 (p<0.001), and higher in group 4 than in group 3 (p<0.01). CONCLUSION: Peritoneal lavage with a 2% lidocaine saline solution without adrenaline, prevented the mortality of all animals with fecal peritonitis.

Effects of peritoneal lavage with lidocaine on survival of rats with fecal peritonitis

PURPOSE: To study the effects of peritoneal lavage with a 2 percent lidocaine solution, on the survival of the rats submitted to peritonitis caused by their own feces. METHODS: Forty-eight Wistar rats, weighting between 300g and 330g (mean, 311,45 ±9,67g), were submitted to laparotomy 6 hours following induction of fecal peritonitis. Animals were randomly divided into four groups of 12 each as follows: 1- Control, no therapy; 2- Drying of the abdominal cavity; 3- Peritoneal lavage with saline and drying; 4- Peritoneal lavage with a 2 percent lidocaine solution and drying. Animals that died were submitted to necropsy and the time of their death recorded; survivors were killed on the post-operation 11th day and necropsied. RESULTS: Death occurred within 52 h in all animals of group 1; within 126 h in 100 percent of those of group 2; within 50 h in 50 percent of those of group 3. All animals of group 4 survived. Survival on the 11 th day was higher in groups 3 and 4 than in groups 1 and 2 (p<0.001), and higher in group 4 than in group 3 (p<0.01). CONCLUSION: Peritoneal lavage with a 2 percent lidocaine saline solution without adrenaline, prevented the mortality of all animals with fecal peritonitis .

OBJETIVO: Estudar o efeito da lavagem peritoneal com solução de lidocaína a 2 por cento na sobrevida de ratos com peritonite fecal por fezes autógenas. MÉTODOS: Foram utilizados 48 ratos Wistar, pesando entre 300g e 330g (M.A 311,45 ±9,67) submetidos à laparotomia 6 horas após a indução de peritonite, distribuídos aleatoriamente em 4 grupos: 1- (n=12) Controle, nenhum tratamento; 2- (n=12) Enxugamento da cavidade abdominal; 3- (n=12) Lavagem da cavidade abdominal com 3 ml de solução salina 0,9 por cento e enxugamento ; 4- (n=12) Lavagem da cavidade abdominal com 30 mg/Kg( ± 0,5 mL) de lidocaína 2 por cento ,sem adrenalina, e 2,5ml de solução salina 0,9 por cento e enxugamento. Os animais que faleceram foram necropsiados e o horário do óbito anotado. Os sobreviventes foram mortos no 11º dia de pós-operatório e realizou-se a necropsia. RESULTADOS: Houve 100 por cento de mortalidade nos animais do grupo 1, em 52 horas; 100 por cento nos animais do grupo 2, em 126 horas e 50 por cento nos animais do grupo 3 em 50 horas. Os animais do grupo 4 sobreviveram. A sobrevida, no 11º dia de pós-operatório, foi maior nos grupos 3 e 4 em relação aos grupos 1 e 2 ( p< 0,001) e maior nos grupos 4 que no grupo 3(p<0,01). CONCLUSÃO: A lavagem peritoneal com lidocaína a 2 por cento sem adrenalina e diluida em 2,5 ml de solução salina, foi eficaz para evitar o óbito, por 11 dias(eutanásia) em 100 por cento dos animais com peritonite fecal.

Effect of oral glutamine administration on oxidative stress, morbidity and mortality in critically ill surgical patients.

OBJECTIVE: To examine the effect of enteral administration of glutamine in patients with peritonitis or abdominal trauma. METHODS: In a prospective, interventional, observer-blind, randomized clinical trial, 120 patients, aged 18-60 years, were randomized to receive either enteral glutamine 45 g/day for 5 days in addition to standard care (n=63; group A) or standard care alone (n=57; group B). Surgical intervention was done as needed. RESULTS: The two groups were comparable for sex and severity of illness scores. Following treatment, serum malondialdehyde (MDA) levels in group A increased from 4.4 (8.0) to 7.2 (4.8) mmol/mL, whereas those in group B decreased from 3.9 (4.9) to 3.1 (5.0) mmol/mL; these changes were not statistically significant. Reduced glutathione levels increased from 0.03 (0.04) to 0.06 (0.12) mg/g Hb (p=0.032) after treatment in group A and from 0.03 (0.03) to 0.05 (0.04) mg/g Hb (p=0.001) in group B. Infectious complications were equally frequent in the two groups (group A: 44; group B: 37; p=0.571). Survival rate and duration of hospital stay were also comparable in the two groups. CONCLUSION: Enteral glutamine supplementation offers no advantage in patients with peritonitis or abdominal trauma.

Change of TH1/TH2 cytokine equilibrium in rats with severe sepsis and therapeutic effect of recombinant interleukin-12 and Shenmai injection.

OBJECTIVE: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI), a Chinese medicinal preparation. METHODS: Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rIL-12 or SMI, the survival rate was recorded and serum levels of TNF-alpha, INF-gamma, and IL-10 before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rIL-12 or SMI, untreated model group, and blank group). RESULTS: Serum and PLF levels of IFN-gamma, TNF-alpha at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter (P < 0.05). IFN-gamma secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P < 0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P < 0.05) and cause significant increase of the serum level and SM secretion of IFN-gamma. CONCLUSION: Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rIL-12 and SMI, may increase the survival rate, and its mechanism may be related with their immuno-stimulating action.

Effect of inappropriate initial empiric antibiotic therapy on outcome of patients with community-acquired intra-abdominal infections requiring surgery.

To assess the significance of initial empiric parenteral antibiotic therapy in patients requiring surgery for community-acquired secondary peritonitis, 425 patients hospitalized between January 1999 and September 2001 in 20 clinics across Germany were followed for a total of 6,521 patient days. Perforated appendix (38%), colon (27%), or gastroduodenum (22%) were the most common sites of infection. Escherichia coli was the most common pathogen. A total of 54 (13%) patients received inappropriate initial parenteral therapy not covering all bacteria isolated, or not covering both aerobes and anaerobes in the absence of culture results. Clinical success, predefined as the infection resolving with initial or step-down therapy after primary surgery, was achieved in 322 patients (75.7%; 95% confidence interval (CI), 70.6-81.2). Patients were more likely to have clinical success if initial antibiotic therapy was appropriate (78.6%; 95% CI, 73.6-83.9) rather than inappropriate (53.4%; 95% CI, 41.1-69.3). Patients having clinical success were estimated to stay 13.9 days in hospital (95% CI, 13.1-14.7), while those who had clinical failure stayed 19.8 days (95% CI, 17.3-22.3). In conclusion, appropriateness of initial parenteral antibiotic therapy was a predictor of clinical success, which in turn was associated with length of stay.