The Effect of Granulocyte Colony-Stimulating Factor in the Treatment of <Emphasis Type="Italic">Escherichia coli</Emphasis> Peritonitis With or Without Ceftriaxone in a Nonneutropenic Rat Model

PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) in the treatment of Escherichia coli peritonitis with and without ceftriaxone in a nonneutropenic rat model. METHODS: The rats were divided into five groups: control group (C) receiving physiological saline; peritonitis group (P) infected intraperitoneally with a live bacterial suspension of E. coli; peritonitis and antibiotic group (PA) receiving ceftriaxone 3 h after being infected; peritonitis, antibiotic, and G-CSF group (PAG) receiving G-CSF and antibiotic 3 h after infection; and peritonitis and G-CSF group (PG). RESULTS: All rats in group C survived. Any animals which did not survive died within 24h after inoculation. A significantly higher rate of survival, 95%, was observed with antibiotic treatment alone (PA), in comparison to the G-CSF-treated groups, PAG and PG, 52% and 57%, respectively. CONCLUSION: No beneficial effect of G-CSF treatment was seen in the E. coli peritonitis and antibiotic therapy remains the basic treatment for this disease.     

Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection

BACKGROUND: Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes. METHODS: This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03). CONCLUSIONS: Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.     

Nimodipine reduces the toxicity of intravenous bupivacaine in rats.

We examined nimodipine modification of bupivacaine toxicity in anesthetized male rats. Three minutes after pretreatment, group 1 (n = 11), group 3 (n = 10), and their respective control groups (n = 11 and n = 9) received intravenous bupivacaine LD50 (median lethal dose). After pretreatment, group 2 (n = 10), group 4 (n = 8), and their respective control groups (n = 10 and n = 8) received intravenous bupivacaine LD90 (90% lethal dose). Pretreatment was 200 micrograms/kg intravenous nimodipine in groups 1 and 2 and 500 micrograms/kg in groups 3 and 4. Control animals were pretreated with intravenous saline solution. Data were analyzed by chi 2-analysis and analysis of variance. Survival increased after 200 micrograms/kg nimodipine (P less than 0.05). In group 1, 9 (81%) of 11 survived compared with control animals (4 [36%] of 11). In group 2, 8 (80%) of 10 survived compared with control animals (2 [20%] of 10). Survival was not increased after 500-micrograms/kg nimodipine pretreatment. In group 3, 2 (22%) of 9 survived compared with control animals (4 [40%] of 10). In group 4, 4 (50%) of 8 survived compared with control animals (2 [25%] of 8). We conclude that nimodipine pretreatment with 200 micrograms/kg protects against fatal toxicity from LD50 and LD90 bupivacaine, but 500 micrograms/kg does not.     

Statin (cerivastatin) protects mice against sepsis-related death via reduced proinflammatory cytokines and enhanced bacterial clearance

BACKGROUND: Death attributable to septic shock syndrome depends highly on the inflammatory response and cytokine production. Inhibition of inflammation is one of the many pleiotropic effects of statins. The aim of this study was to test the hypothesis that statins have a role in altering the host response to bacterial infections and thus would prove beneficial in the prevention of microbial sepsis. METHODS: Male C57BL/6 and C3H/HeN mice received cerivastatin (4 mg/kg) or phosphate-buffered saline (PBS) intraperitoneally (i.p.), 24 and 1 h before and 24, 48, and 72 h after bacterial challenges. Sepsis was induced by i.p. injection of lipopolysaccharide (LPS) (45 mg/kg), Staphylococcus aureus (5 x 10(7) colony-forming units [CFU]/mouse), or Salmonella typhimurium (2.5 x 10(6) CFU/mouse). RESULTS: Administration of cerivastatin improved significantly the survival rate of mice challenged with LPS (31% vs. 19% in the PBS group; p = 0.001), S. aureus (56% vs. 20% in PBS group; p = 0.01), or S. typhimurium (48% vs. 10% in PBS group; p = 0.03). Significantly reduced release of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was evident in cerivastatin-treated mice after LPS challenge. Cerivastatin-treated mice showed insignificant reductions in serum TNF-alpha and IL-6 concentrations after bacterial challenge. However, significantly accelerated bacterial clearance was demonstrated in cerivastatin-treated mice 24 h after S. typhimurium infection and 48 h after S. aureus infection. CONCLUSIONS: Cerivastatin protects mice against LPS- and live bacteria-induced death, an effect associated with cerivastatin-attenuated pro-inflammatory cytokine production and enhanced bacterial clearance. Hence, application of statins in the clinical setting may prove beneficial in prevention of LPS or bacterial infection-related sepsis.     

Impaired bacterial clearance and trapping in obstructive jaundice.

Sepsis is a major cause of mortality in patients with common bile duct obstruction. To define possible contributing factors to this phenomenon, this study evaluates the effect of biliary obstruction on the intravascular clearance and organ trapping of viable Escherichia coli using a rat model. Adult male Sprague-Dawley rats were placed in three groups: Group I controls had sham operation, Group II had division and ligation of common bile duct (CDL), and Group III underwent splenectomy. At 21 days following operation 10(9) radiolabeled E. coli were injected intravenously. At varying intervals after infusion, blood samples were obtained for clearance study. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined (expressed as the mean percentage of injected viable E. coli). Intravascular clearance was similar in all groups. There was a significant decrease in the trapping of bacteria by the liver of CDL rats 14.5% +/- 4.95 (vs. control = 70.0% +/- 13.3) (p less than 0.005). A significant increase of bacterial trapping by the lung was observed in the CDL animals: 63.1% +/- 7.06 (vs. controls 1.4% +/- 0.82) (p less than 0.005). There was no significant change in bacterial localization in splenectomized rats. These data suggest that biliary obstruction decreases hepatic phagocytosis and increases pulmonary localization of viable E. coli. As the Kupffer cells of the liver are usually effective in removal of blood borne bacteria, this phagocytic dysfunction may contribute to the increased susceptibility to infection noted in instances of biliary obstruction.     

Deleterious Effects of Mild Hypothermia in Septic Rats Are Ameliorated by Granulocyte Colony-stimulating Factor

Background: The authors studied the effects of mild hypothermia on the outcome in a rat model of intraabdominal sepsis and tested whether granulocyte colony-stimulating factor (G-CSF) augments the host response and improves outcome during mild hypothermia.

Methods: A rat model of peritoneal contamination and infection with human stool bacteria was used to simulate clinical trials that included increasing complexity. In trial 1, postoperative hypothermia (32[degrees]C) was compared with normothermia (38[degrees]C), without supportive treatment (10 rats per group). In trial 2, with a more severe infection, rats were given antibiotic prophylaxis. Using 20 rats per group, the authors compared postoperative hypothermia (32[degrees]C), normothermia, and postoperative hypothermia (32[degrees]C) with 20 [mu]g/kg G-CSF prophylaxis given 12 h before surgery and 12 h and 36 h after surgery. The primary endpoint was death at 120 h. Secondary endpoints were systemic cytokine concentrations, leukocyte counts, and the phagocytic activity of granulocytes and monocytes.

Results: In trial 1, 50% of the normothermia group and 10% of the postoperative hypothermia group survived. In trial 2, 50% of the normothermia group, 20% of the hypothermia group, and 60% of the hypothermia plus G-CSF group survived. Postoperative hypothermia plus G-CSF reduced plasma concentrations of interleukin-6 (hypothermia group, 511 +/- 104 pg/ml; hypothermia plus G-CSF group, 247 +/- 51 pg/ml) and macrophage inflammatory protein-2 (hypothermia group, 239 +/- 43 pg/ml; hypothermia plus G-CSF group, 178 +/- 21 pg/ml).     

Protection with antibody to tumor necrosis factor differs with similarly lethal Escherichia coli versus Staphylococcus aureus pneumonia in rats

BACKGROUND: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia. METHODS: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h. RESULTS: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > or = 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6; P = 0.006) and S. aureus (-0.5 +/- 0.04; P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < or = 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003). CONCLUSION: Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type.     

Effects of Granulocyte-Colony Stimulating Factor on the Polymorphonuclear Leukocyte Activity and the Course of Sepsis in Rats with Experimental Peritonitis

Purpose Polymorphonuclear leucocytes (PML) play an essential role in the host immune response to severe infections. The effects of granulocyte-colony stimulating factor (G-CSF) on the PML immune functions during serious abdominal infection and course of sepsis, and on the survival in rats with peritonitis are the main subjects of this study. Methods The first phase of the study was carried out on 30 Wistar-albino rats equally divided into three groups; Group 1 (control) sham laparotomy; Group 2 (peritonitis); and Group 3 (peritonitis+G-CSF) with fecal peritonitis created by a cecal puncture. At postoperative hours 3, 12, and 24, 0.5 ml normal saline was injected subcutaneously in groups 1 and 2, and 0.5 ml solution containing 50 μg/kg of G-CSF in group 3. The phagocytic and chemotactic activities of neutrophils and monocytes were evaluated by a flow cytometry analysis. The plasma lactate concentrations were assessed as a marker of tissue perfusion during sepsis. The second phase was a survival analysis, which was observed during 10 days on 20 rats equally divided into two groups; group 1 (peritonitis) and group 2 (peritonitis+G-CSF). 0.5 ml normal saline in group 1 and 50 μg/kg of G-CSF in group 2 was injected subcutaneously at the 3rd hour and twice daily. Results Both the neutrophil- (1.636 vs 2.236) and monocyte-related (1.789 vs 2.465) phagocytic activities significantly (P < 0.001) improved after the G-CSF administration in the rats with peritonitis. In addition, the G-CSF treatment significantly (P < 0.0014) improved the chemotactic activity (1.18 vs 2.75) of neutrophils, and partly supported (P < 0.0952) the chemotactic activity (1.69 vs 2.37) of monocytes. The plasma lactate level (1.86 vs 4.9 mmol/l) was significantly (P < 0.0001) increased after septic changes due to experimental peritonitis. On the other hand, the lactate concentration was significantly (P < 0.001) decreased (4.9 vs 2.63 mmol/l) after the G-CSF administration. The survival was 20% at the 4th day and 0 at the 6th day in peritonitis, and 90% at the 4th day (P = 0.0055) and 80% at the 6th day (P = 0.0007) days in the peritonitis+G-CSF groups. Conclusion G-CSF enhances the immune functions of neutrophils and monocytes. The increased activities of these cells have a beneficial effect on the enhancement of the host immune response during severe infections. The improved immune function of PML due to the G-CSF treatment thus ameliorates the survival and the courses of sepsis, which is also defined by tissue perfusion and the cellular oxygen balance, which is affected by septic changes.     

Protection with Antibody to Tumor Necrosis Factor Differs with Similarly Lethal Escherichia coli versus Staphylococcus aureus Pneumonia in Rats

Background: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia.

Methods: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h.

Results: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P >= 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6;P = 0.006) and S. aureus (-0.5 +/- 0.04;P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P <= 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003).     

新生儿重症监护室多重耐药菌感染临床分析及高危因素

目的探讨新生儿重症监护室(NICU)新生儿多重耐药菌(MDRO)感染的高危因素及其预防策略。方法收集2019年1月至2020年12月中山大学附属第七医院NICU住院新生儿中病原体培养阳性患儿的临床资料,其中检出MDRO的新生儿为MDRO组(25例),检出非MDRO的新生儿为非MDRO组(45例),回顾性分析MDRO构成比、菌种、检出部位及耐药情况,并分析两组新生儿的疾病及转归,采用单因素分析和多因素Logistic回归分析MDRO感染的高危因素。结果714份送检标本中分离出细菌70株,其中MDRO 25株(35.7%)。MDRO中革兰阳性球菌15株(60.0%),其中凝固酶阴性葡萄球菌12株(48%),耐甲氧西林金黄色葡萄球菌3株(12.0%);革兰阴性杆菌10株(40.0%),其中产超广谱β-内酰胺酶大肠埃希菌6株(24.0%)。单因素分析显示两组新生儿的绒毛膜羊膜炎发生率[16(64.0%)vs.17(37.7%):χ^(2)=4.435、P=0.035]、联合使用2种以上抗菌药物[10(40.0%)vs.8(17.7%):χ^(2)=4.155、P=0.042]、肠外营养时间超过2周[15(60.0%)vs.15(33.3%):χ^(2)=4.667、P=0.031]差异均有统计学意义。多因素Logistic回归分析显示,绒毛膜羊膜炎为NICU新生儿MDRO感染的独立危险因素(OR=2.899、95%CI:1.007~8.350、χ^(2)=3.889、P=0.049)。MDRO组患儿主要感染疾病为新生儿败血症[6例(24.0%)]和新生儿肺炎[6例(24.0%)];非MDRO组患儿主要感染疾病为化脓性脑膜炎[2例(4.4%)]和新生儿肺炎[2例(4.4%)]。MDRO组患儿感染率高于非MDRO组[14(56.0%)vs.5(11.1%):χ^(2)=16.376、P<0.001],两组患儿住院转归[24(96.0%)vs.43(95.5%):χ^(2)=0.000、P=1.000]、住院时间[21.0(7.5,37.0)d vs.8.0(4.0,35.5)d:Z=-1.793、P=0.073]以及住院费用[3.588(1.0395,8.7050)万元vs.1.3713(0.7287,7.6127)万元:Z=-1.189、P=0.234]差异均无统计学意义。结论NICU患儿MDRO感染率较非MDRO高,绒毛膜羊膜炎为NICU新生儿MDRO感染独立危险因素。应从积极处理母亲羊膜炎、围产期抗菌药物合理使用、加强感染控制等方面进行NICU新生儿MDRO感染管理。     

Clinical management of dialysis catheter-related bacteremia with concurrent exit-site infection

Dialysis catheter-related bacteremia (CRB) can frequently be treated with systemic antibiotics, in conjunction with an antibiotic lock, in an attempt to salvage the catheter. It is unknown whether CRB associated with an exit-site infection can be treated with such an approach. We retrospectively queried a prospective, computerized vascular access database, and identified 1436 episodes of CRB, of which 64 cases had a concurrent exit site. The frequency of concurrent exit-site infection was 9.6% with Staphylococcus epidermidis, 6.1% with Staphylococcus aureus, and only 0.7% with Gram negative CRB (p < 0.001 for Staphylococcus vs. Gram negative rods). Five serious complications (four major sepses and one endocarditis) occurred in 24 patients with S. aureus infection, but none in 32 episodes of S. epidermidis infection (p = 0.01). Catheter survival was significantly shorter in patients with S. aureus infections. The median catheter survival (without infection or dysfunction) was 14 days with S. aureus vs. 30 days with S. epidermidis infection (p = 0.035). In conclusion, concurrent exit-site infection is seen most commonly in association with Staphylococcal CRB. When the infecting organism is S. epidermidis, attempted salvage with systemic antibiotics and an antibiotic lock is reasonable. However, prompt catheter removal is indicated when the pathogen is S. aureus.     

Clinical patterns of surgical endocarditis

BACKGROUND: This study was aimed at defining clinical and anatomic patterns in cases of surgical endocarditis (SE). METHODS: SE cases done between 1981 and 1997 at our metropolitan county hospital were retrospectively analyzed. RESULTS: A total of 106 consecutive episodes of SE involving 125 valves in 100 patients were studied. SE included 71 aortic, 42 mitral, and 12 tricuspid valves. The etiologies included intravenous drug abuse (IVDA) in 48 (45%) and dental source in 30 (28%). A congenitally deformed valve was present in 19 (18%). Compared to non-IVDA, IVDA episodes of SE were more often superimposed on previously normal valves (38/48 [79%] vs. 30/58 [52%])**, S. aureus infections (17/43 [40%] vs. 9/54 [17%])*, active endocarditis (38/48 [79%] vs. 32/58 [55%])*, and surgically treated on an urgent basis (10/48 [21%] vs. 4/58 [7%])*. Overall, macroemboli occurred in 53 (50%) of SE and was associated with pseudoaneurysm*, preoperative neurologic dysfunction,** and operative death.** The operative mortality (defined by Society of Thoracic Surgeons) for SE was 5/106 (4.7%). Macroembolism,** aortoventricular discontinuity,** abscesses,* pseudoaneurysm,** and preoperative renal failure* were associated with mortality. Prosthetic valve endocarditis was present in 10 of 106 episodes of SE (9.4%). *p < or = 0.05; **p < or = 0.01. CONCLUSION: (1) The aortic valve is most commonly associated with SE, (2) SE of a previously normal valve is more likely to occur with IVDA than other etiologies, (3) macroemboli occur in half of SE and is associated with an increased operative mortality.     

Anti-microbial locks increase the prevalence of Staphylococcus aureus and antibiotic-resistant Enterobacter: observational retrospective cohort study

Background Anti-microbial lock solutions (AML), in conjunction with systemic antibiotics, may successfully treat tunnelled haemodialysis catheter-related bloodstream infections (CR-BSI). It is unknown whether AML promote anti-microbial resistance. Methods This is a retrospective cohort study of all CR-BSI (2003-2006) in our dialysis unit. Controls (n = 265) were treated with systemic vancomycin and gentamicin. In addition to the systemic antibiotics, the study group (n = 662) received AML containing vancomycin and gentamicin during inter-dialytic periods. Antibiotic sensitivity/resistance profiles of all organisms were analysed. Changes in the incidence of infection (chi-square test) and resistant organisms (Fisher's exact test) were calculated. Results The incidence of CR-BSI decreased from 8.50/1000 catheter days (controls) to 3.80 (study group; P < 0.0001), and the incidence of relapses decreased (P = 0.0027). The number needed to treat to prevent subsequent bacteraemia using an AML adjunct is 3 ± 0.4. The proportion of Gram-positive cultures increased (P < 0.0001), including Staphylococcus aureus (P = 0.03), but the proportion of methicillin-resistant S. aureus (P = 0.87) and vancomycin resistance (P = 0.90) did not. Increased gentamicin resistance (P < 0.0001) and ciprofloxacin resistance (P = 0.04) were observed in Gram-negative cultures. Gentamicin resistance [relative risk (RR) > 15.29; P < 0.0001] and ciprofloxacin resistance (RR = 6; P = 0.007) increased in Enterobacter species, but not Pseudomonas or Escherichia coli species. Conclusion AML decrease CR-BSI incidence, although proportions of S. aureus and anti-microbial-resistant Enterobacter are increased.     

Risk factors for Staphylococcus aureus infection in liver transplant recipients.

Staphylococcus aureus is the leading cause of bacterial infection in liver transplant recipients. Preoperative nasal carriage of methicillin-resistant S. aureus (MRSA) is associated with a high risk of infection. We conducted a retrospective cohort study in order to identify independent risk factors for early-onset S. aureus infection after liver transplantation. Patients were screened preoperatively for methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage. Risk factor analysis was performed by univariate analysis followed by stepwise logistic regression. Of the 323 patients included, 63 (19.5%) patients developed S. aureus infection (36 MRSA, 27 MSSA) within 1 month of surgery. Variables significantly associated with infection in the univariate analysis were MRSA and MSSA nasal carriage, alcoholic cirrhosis, absence of hepatocellular carcinoma, decreased prothrombin ratio, and presence of ascites. In the multivariate analysis, MRSA carriage (odds ratio [OR]: 20.9, P < 0.0001), MSSA carriage (OR: 3.4, P = 0.0004), alcoholic cirrhosis (OR: 2.4, P = 0.01) and decreased prothrombin ratio (OR: 1.2, P = 0.01) were independent predictors of infection. Molecular typing showed that the infecting isolate was identical to the isolate from the nose in most patients. In conclusion, preoperative nasal carriage of MRSA and MSSA is an independent risk factor for S. aureus infection in liver transplant recipients. The infection is most often of endogenous origin. Alcoholic cirrhosis and the severity of liver failure are also associated with a high risk of infection.     

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post-transplant antibody deficiency and severe infections

IgG hypogammaglobulinemia is a risk factor for infection in heart recipients. We assessed reconstitution of humoral immunity after non-specific intravenous immunoglobulin (IVIg) replacement therapy administered to treat secondary IgG hypogammaglobulinemia in heart recipients with severe infections. The study population comprised 55 heart recipients who were administered IVIg (IVIg group) and 55 heart recipients with no severe infectious complications (control group). An event was defined as a severe infection requiring intravenous drug therapy during the first year after transplantation. The IVIg protocol comprised non-specific 5% pasteurized IVIg at a dose of 300-400 mg/kg/months. IgG titers were lower in the IVIg group than in controls at seven d (577 vs. 778 mg/dL, p < 0.001) and at one month (553 vs. 684, p = 0.003). After IVIg therapy, IgG concentrations were similar in both groups at three months (681 vs. 737, p = 0.25) and at six months (736 vs. 769, p = 0.46). At three months, the IVIg group had higher levels of antitetanus toxoid and anti-HBs (ELISA, 2.07 ± 2.11 vs. 0.60 ± 1.24 mg/dL [p = 0.003] and 42 ± 40 vs. 11 ± 31 IU/mL [p = 0.005], respectively) than controls. The mean number of infectious complications was significantly lower after IVIG therapy in the IVIG group. IVIg was associated with restoration of humoral immunity in heart recipients with post-transplant IgG hypogammaglobulinemia and severe infections.     

Effects of Perfluorohexan Vapor on Gas Exchange, Respiratory Mechanics, and Lung Histology in Pigs with Lung Injury after Endotoxin Infusion

Background: Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs.

Methods: Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg [middle dot] kg-1 [middle dot] h-1 for 1 h and 10 [mu]g [middle dot] kg-1 [middle dot] h-1 for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n = 7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion.

Results: After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin).     

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.     

Anterograde fast component of axonal transport during insulin-induced hypoglycemia in nondiabetic and diabetic rats

To elucidate the pathogenesis of the peripheral neuropathy associated with hypoglycemia the anterograde fast component (aFC) of axonal transport was studied in nondiabetic rats during acute and prolonged insulin-induced hypoglycemia and in streptozocin-diabetic (STZ-D) rats with acute hypoglycemia. [35S]methionine and [3H]fucose were injected into the dorsal root ganglion (L5) to label protein and glycoprotein, respectively. During the 4 h of transport, thigh temperature was maintained constant. Acute severe hypoglycemia (1.5 +/- 0.2 mM) was associated with a 36% decrease in the amount of aFC (2.3 +/- 0.7% in the test group vs. 3.6 +/- 0.8% in the controls), whereas transport velocity was unaffected. Prolonged hypoglycemia, obtained by pretreatment with insulin for 3 days, prevented the decrease in amount of aFC. In STZ-D rats, acute severe hypoglycemia (1.5 +/- 0.6 mM) produced a similar but less-pronounced decrease of aFC. We conclude that hypoglycemia is associated with alterations in axonal transport that could play a role in development of neuropathy. Prolonged hypoglycemia protects axonal transport against the effects of glucopenia, and an untreated diabetic state maintained for several days has a partially protective effect against episodes of hypoglycemia.     

An analysis of ten-year trends in infections in adults on continuous ambulatory peritoneal dialysis (CAPD)

Infectious complications are the Achilles heel of CAPD. To determine trends in these events, we analyzed the CAPD related infections of 303 adults on CAPD at a single university center between 1979 and 1989. During this decade the percentage of insulin-dependent diabetics increased from 14% to 39% (p less than 0.005). Peritonitis rates fell from 2.4 episodes/y in 1979 to 0.8 episodes/y in 1989. The proportion of patients with multiple episodes of peritonitis decreased (40% of the patients in 1979-1982 vs 15% in 1983-1989, p = 0.0001) while the proportion of patients with no episodes of peritonitis increased during the same periods (29% vs 49%, p = 0.005). The proportion of peritonitis episodes due to S. aureus rose over the 10-year period (p = 0.005), while those due to S. epidermidis decreased (p less than 0.10). The overall incidence of S. aureus peritonitis remained unchanged. Catheter infection rates initially increased and then fell during the decade; S. aureus remained the predominant cause. The proportion of peritonitis episodes associated with catheter infection rose (13% in 1982 vs 24% in 1989, p = 0.025), and in 1989, 80% of these episodes were caused by S. aureus. Catheter loss was also primarily due to S. aureus infections in 1989 (80%). Infections due to P. aeruginosa were a persistent problem. The proportion of patients transferring to hemodialysis each year paralleled catheter loss rates, which in turn appeared to be more related to catheter infection rates than to peritonitis rates. We conclude that control of S. aureus and P. aeruginosa will be the key to future reductions in the infectious complications of CAPD patients.     

Primary and secondary healing in infected wounds. An experimental study

The beneficial effects of delayed closure of contaminated wounds are recognized, but not well defined. Rats with abdominal incisions were infected with Staphylococcus aureus or Escherichia coli and then subgrouped for primary or secondary healing. Noninfected rats served as controls. Between seven and 119 days later, the wounds were subjected to breaking-strength determination, hydroxyproline analysis, and light and scanning electron microscopy. In the controls, secondary closure gave stronger wounds than primary closure. In those infected with S aureus the wounds were stronger than in the primary-closure control group, regardless of the closure method. Of the E coli-infected wounds those primarily closed were weaker than those secondarily closed. Secondary closure gave infected wounds fewer complications. Biochemical and microscopic examination did not explain these findings.