Granulocyte colony-stimulating factor but not peritoneal lavage increases survival rate after experimental abdominal contamination and infection

BACKGROUND: The value of peritoneal lavage for intra-abdominal contamination and infection has never been proven scientifically. In contrast, the stimulation of host defence mechanisms with cytokines such as granulocyte colony-stimulating factor (G-CSF) has appeared promising in recent clinical trials. METHODS: Clinic modelling randomized trials (CMRTs), which model the complexity of the clinical reality, were used in rats in which peritoneal contamination and infection (PCI) was produced with human stool bacteria. The following groups were compared: trial 1, intraoperative peritoneal lavage with saline versus taurolin (18 rats per group); trial 2, no lavage versus saline lavage versus saline lavage plus subcutaneous administration of G-CSF (18 rats per group); trial 3, lavage with saline versus no lavage (30 rats per group). The primary endpoint was mortality at 120 h. Secondary endpoints were the phagocytic activity of granulocytes, and systemic and peritoneal cytokine levels. RESULTS: In trial 1 lavage with taurolin was not superior to that with saline (five of 18 versus eight of 18 animals survived; P = 0.32). In trial 2, six of 18 animals having no lavage and three of 18 receiving saline lavage survived. The combination of lavage and G-CSF increased the number of animals surviving to 11 of 18 (P < 0.05). Lavage combined with G-CSF stimulated granulocyte phagocytic activity (P < 0.01) and reduced the levels of interleukin (IL) 6 (P < 0.01) and tumour necrosis factor alpha (P < 0.05) in peritoneal fluid, as well as plasma levels of IL-6 (P < 0.05) and IL-10 (P < 0.01). In trial 3, survival was not significantly different in animals having lavage (14 of 30) and no lavage (19 of 30) (P = 0.14). CONCLUSION: In these CMRTs of intra-abdominal contamination and infection, peritoneal lavage was not beneficial, but when lavage was combined with subcutaneous administration of G-CSF mortality was reduced and the local and systemic cytokine response was downgraded. Results from these CMRTs were used directly to define the trial conditions of a randomized clinical trial with G-CSF. Peritoneal lavage is not recommended.     

Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis

Multiple immune defects have been demonstrated following thermal injury, including defective granulocyte production and function. Recombinant human granulocyte colony-stimulating factor (rhGCSF) is a regulator of the myelopoietic system. The effect of rhGCSF administration on survival and on the myelopoietic system in a murine model of Pseudomonas burn wound sepsis was investigated. Male BDF1 mice that underwent a 15% total body surface area burn injury and burn wound seeding with 1 x 10(8) Pseudomonas aeruginosa organisms demonstrated an improved mean survival time with the subcutaneous administration of 100 ng of rhGCSF twice a day. Mice that underwent a similar thermal injury and burn wound seeding with 3 x 10(7) P aeruginosa organisms demonstrated an augmented myelopoietic response through the administration of rhGCSF, as represented by significantly increased white blood cell count, neutrophil count, splenic weight, femoral marrow cellularity, and femoral marrow granulocyte-macrophage colony-forming cell count. Myelopoietic augmentation through rhGCSF administration may serve to decrease the morbidity of septic events following thermal injury.     

Antibiotic prophylaxis for group A streptococcal burn wound infection is not necessary

BACKGROUND: Historically, group A beta-hemolytic streptococci (GAS) burn wound infection has been a major source of morbidity and mortality in burn patients and has prompted the prophylactic administration of antibiotics to children with burns. Wound monitoring, surveillance cultures, and early excision of deep wounds may have changed this. Our objective in this project was to determine the efficacy of routine antibiotic prophylaxis in the era of early excision and closure of deep burn wounds. METHODS: Two cohorts of burned children were compared: all children admitted during calendar years 1992 through 1994 (group 1) and during calendar years 1995 through 1997 (group 2). All group 1 children received routine GAS antibiotic prophylaxis. Only those group 2 children with documented positive admission or surveillance cultures for GAS were treated. RESULTS: There were 511 children in group 1 and 406 children in group 2. They were well matched for age (4.7 +/- 0.21 years vs. 5.3 +/- 0.26 years, p = 0.06) and burn size (11.0% +/- 0.7% vs. 12.4% +/- 0.8%, p = 0.18). GAS species were recovered at admission or during hospitalization from 11 (2.6%) of group 1 children and 18 (4.4%) of group 2 children (p = 0.05), indicating a marginally higher rate of carriage in group 2. Nevertheless, in group 1 there were three (0.6%) who developed GAS wound infection and in group 2 there were four (0.98%, p = 0.71). The incidence of GAS infection in those patients with positive admission cultures was three (27%) of group 1 and four (22%) of group 2. No child developed fulminant GAS infection. CONCLUSION: Routine antibiotic prophylaxis of burn wounds in children in not effective in further reducing a low baseline incidence of GAS wound infection if admission screening by culture is used to identify those children who carry the organism and early excision of deep burns is practiced.     

The beneficial effect of granulocyte colony-stimulating factor (G-CSF) in combination with gentamicin on survival after Pseudomonas burn wound infection

Inadequate granulopoiesis and decreased granulocyte function are thought to play a significant role in the burned victim's susceptibility to infection. In an attempt to determine whether the regulatory granulopoietic growth factor G-CSF could favorably affect survival when used in combination with antibiotics, we examined survival in a murine model of Pseudomonas aeruginosa burn wound infection. One hundred twenty male BDF1 mice received a 15% total body surface area burn and were randomized to one of five treatment groups: (1) burn only, (2) burn + infection, (3) burn + infection + G-CSF, (4) burn + infection + gentamicin, and (5) burn + infection + G-CSF + gentamicin. Infected mice received a 10(3) colony-forming units topical inoculum of Pseudomonas to the wound immediately postburn. Gentamicin animals received 6.0 mg/kg intraperitoneal gentamicin as a single dose immediately postburn. G-CSF was administered as 100 ng twice daily for 7 days. All treatment groups showed improved survival compared with the burn + infection group, which showed 100% mortality by day 9 (p less than 0.001 all groups; Cox-Mantel statistic). Group 5 (burn + infection + G-CSF + gentamicin) exhibited improved survival as compared with either group 3 (burn + infection + G-CSF, p = 0.054) or group 4 (burn + infection + gentamicin, p = 0.007). The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.     

Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis

The presence of certain defects in both cellular and humoral immunity after thermal injury has been established. Likewise, the translocation of enteric bacteria to the mesenteric lymph nodes and to distant organs has also been observed following serious thermal injury. The effects of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa, and cecal bacterial content were investigated in a rat model of burn wound sepsis in which albino Wistar rats were scalded over 30% of their bodies, after which the lesions were infected by 1×10⁸ colony-forming units (cfu)Pseudomonas aeruginosa. The control group was treated with 5% dextrose solution subcutaneously starting 2 days preburn, while the treatment group received 100μg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were killed to examine the bowel and culture of the mesenteric lymph nodes (MLN), livers, and spleens. No significant differences were observed between the groups regarding the cecal bacterial content and small bowel; however, a difference was seen in the ratio of translocation in the MLN liver and spleen and quantitative MLN cultures. Based on these findings, G-CSF was thus found to be significantly effective in reducing bacterial translocation due to burn wound sepsis.     

Fungal wound infection (not colonization) is independently associated with mortality in burn patients

OBJECTIVE: To analyze the occurrence of fungal wound infection (FWI) after thermal injury and its relationship to mortality. BACKGROUND: FWI is an uncommon but potentially lethal complication of severe thermal injury. METHODS: The records of patients with thermal burns admitted to a single burn center (1991-2002) were reviewed. Analyses accounted for total burn size (TBS, percentage body surface area), full-thickness burn size (FTBS, percentage body surface area), age, inhalation injury, sex, and fungal-status category. Fungal colonization and infection were determined histopathologically. RESULTS: Criteria for inclusion were met by 2651 patients. Each patient's fungal-status category was defined according to the deepest level of fungal involvement observed during the hospital course: no fungus (2476 patients), fungal wound colonization (FWC, 121 patients), or fungal wound infection (FWI, 54 patients). Median TBS (9%, 47%, 64%, respectively) and mortality (5%, 27%, 76%, respectively) varied significantly among fungal-status groups. Logistic regression was used to detect significant independent associations. FWI was associated with higher TBS. Mortality was associated with TBS, FTBS, inhalation injury, FWI, and age. Unlike FWI, FWC was not independently related to mortality, the greater observed mortality in FWC being explained by other variables such as TBS. The odds ratio for FWI (8.16) suggested about the same mortality impact as augmenting TBS by 33%. A midrange TBS of 30% to 60% was required for most of the detectable association of FWI with mortality. CONCLUSIONS: FWI accompanies larger burns and is associated with mortality in burn patients, particularly in those with TBS 30% to 60%. This association is independent of burn size, inhalation injury, and age.     

Deep postoperative wound infection after carpal tunnel release

Between January 1976 and December 1985, 3620 carpal tunnel releases were done at the Mayo Clinic. A deep postoperative infection developed in 17 (0.47%) patients. These 17 were compared control group of 102 patients to identify possible risk factors. Statistically significant risk factors included intraoperative instillation of steroid solution into the carpal canal, flexor tendon synovectomy, prolonged operative time, and use of a surgical drain. Infection incidence was 0.87% in males and 0.25% in females (statistically significant). Seven (41%) of the 17 patients had a suboptimal result at final follow-up.     

Human mitochondrial oxidative capacity is acutely impaired after burn trauma

BACKGROUND: Mitochondrial proteins and genes are damaged after burn injury in animals and are assessed in human burn patients in this study. METHODS: The rates of maximal muscle mitochondrial oxidative capacity (adenosine triphosphate production) and uncoupled oxidation (heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns on more than 40% of their body surface area and from 13 healthy children controls. RESULTS: Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared with controls (4.0 +/- .2:1.9 +/- .1 micromol O2/citrate synthase activity/mg protein/min pyruvate; control:burn; P < .001 and 3.0 +/- .1: .9 +/- .03 micromol O2/citrate synthase activity/mg protein/min palmityl CoA; control:burn; P = .003). Uncoupled oxidation was the same between groups. CONCLUSIONS: The maximal coupled mitochondrial oxidative capacity is severely impaired after burn injury, although there are no alterations in the rate of uncoupled oxidative capacity. It may be that the ratio of these indicates that a larger portion of energy production in trauma patients is wasted through uncoupling, rather than used for healing.     

Fungal infection of the burn wound

Six of 92 patients with invasive mycotic infection of the burn wound survived. These patients demonstrate the value of prompt diagnosis and expeditious debridement of the infected tissue in successfully managing this dangerous infection.     

粒细胞集落刺激因子治疗下肢缺血性疾病

目的探讨粒细胞集落刺激因子(rhG-CSF)对下肢缺血模型血管新生的影响。方法制作兔左下肢缺血模型,术后随机分为rhG-CSF治疗实验组(n=24)和对照组(n=24);应用流式细胞学技术、动脉造影、免疫组织化学染色检查,比较两组外周血CD34 细胞的含量、缺血下肢侧枝血管计数及肌肉毛细血管密度。结果治疗后3 d实验组CD34 含量(%)为(0.7150±0.0873)明显高于对照组(0.3983±0.0853),差异有统计学意义(P<0.01);实验组在第15、30天时侧枝血管计数(6.33±0.82、9.17±0.75)均高于对照组(3.33±0.52、4.17±0.75)(P<0.01);第40天实验组内收肌毛细血管密度平均为8.5/HP,明显高于对照组4.2/HP(P<0.01)。结论rhG-CSF可以增加兔缺血下肢的毛细血管数量,有促进血管新生的作用。     

重组人粒细胞巨噬细胞集落刺激因子凝胶剂对深Ⅱ度烧伤创面溶痂及愈合影响的临床研究

目的通过临床对比研究,探讨重组人粒细胞巨噬细胞集落刺激因子(recombinant human granulocyte-macrophage colony-stimulating factor,rhGMCSF)凝胶剂对深Ⅱ度烧伤创面溶痂及愈合的作用及其机制。方法以2008年12月-2010年12月收治的符合选择标准的58例深Ⅱ度烧伤患者作为试验对象。男36例,女22例;年龄12～67岁,平均32.4岁。热液烫伤38例,火焰烧伤20例。受伤至治疗时间为1～3d,平均2.1d。采用随机双盲、自身对照方法,分为给予rhGMCSF凝胶剂治疗组(试验组)及不含rhGMCSF的凝胶剂基质治疗组(对照组)。两组用药面积比较差异无统计学意义(P>0.05),具有可比性。用药后观察创面情况,于2、6、10、14、18d计算创面溶痂率,记录完全溶痂时间及创面愈合时间。结果与对照组相比,试验组用药4d后黄白色坏死组织或痂皮逐渐变软;6d后坏死组织易浮动而脱落或痂皮边缘翘起,基底红白相间,深层肉芽组织增长迅速;8d时痂皮基本溶解。用药2d后试验组创面溶痂率即高于对照组,除用药后18d,其余各时间点两组创面溶痂率比较差异均有统计学意义(P<0.05)。试验组完全溶痂时间为(7.71±2.76)d,较对照组(14.71±3.63)d明显缩短(t=13.726,P=0.000);创面愈合时间为(18.41±2.47)d,亦较对照组(23.58±3.35)d明显缩短(t=15.763,P=0.000)。结论 rhGMCSF凝胶剂与单纯凝胶剂基质相比能促进深Ⅱ度烧伤创面坏死组织脱落,加快创面愈合。     

Granulocyte colony-stimulating factor producing undifferentiated carcinoma of urinary bladder: a case report

A case of bladder cancer producing granulocyte colony-stimulating factor (G-CSF) is reported. A 94-year-old woman with a progressive, grade 3 undifferentiated carcinoma, showed marked leukocytosis (maximum 29,780/mm3) with an elevated G-CSF (420 pg/ml). Immunohistochemical examination with monoclonal antibody specific for G-CSF revealed positive staining. Further examination for epidermal growth factor receptor (EGF-R) and p53 were both positive and Ki67 index were 40.7%. These data suggested that this tumor had extremely aggressive growing nature, as the biological character is this.     

Aspergillus infection of the burn wound.

During a 15-year period, 18 patients with major burns developed a wound infection due to Aspergillus. Ages averaged 28 years, extents of burn were 54% (14-97%) BSA for total surface involvement and 42% (14-85%) BSA for full-thickness injury. Pseudomonas sepsis preceded Aspergillus infection in 16 cases. Thirteen of the episodes occurred in three epidemics, each apparently related to contaminated air-conditioner ducts and filters. Treatment was based upon wound excision in all 18 patients, with recurrence initially in each. Topical and parenteral antifungal agents were never individually successful in controlling the infection. Whenever fungal sepsis involved an extremity alone and thus amputation could rid the body of the entire infected site, survival could then be achieved. The overall mortality rate was 78%. Protection of the wound from Aspergillus colonization appeared to be the only reliable method of preventing this often lethal fungus infection.