Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group.

OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. CONCLUSIONS: These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.

Pharmacokinetics of once-daily dosing of gentamicin in surgical intensive care unit patients with open fractures.

OBJECTIVE: To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically. METHODS: Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means. RESULTS: Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 mumol/L; and APACHE II score 13 versus 10. The mean +/- SD (micrograms/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 +/- 19.0 versus 10.1 +/- 1.77; 17.0 +/- 2.7 versus 5.4 +/- 0.4, and 0.45 +/- 0.31 versus 0.69 +/- 0.11, respectively. Area under the curve0-infinity (AUC0-infinity), apparent volume of distribution, and half-life were: 89.0 +/- 28.9 versus 26.1 +/- 1.2 mg.h/L, 0.40 +/- 0.10 versus 0.47 +/- 0.14 L/kg, and 4.0 +/- 1.1 versus 4.3 +/- 1.5 h, respectively. CONCLUSIONS: The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-infinity compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.

Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia.

Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence.

The pull-through procedure: technical factors in influencing outcome, with emphasis on pouchitis.

BACKGROUND: The purpose of the study was to review those features that we believed to be critical to the successful performance of the ileal pouch-anal anastomosis, or pull-through, procedure, and specifically the complication of pouchitis. METHODS: The charts of 205 patients who successfully underwent ileal pouch-anal anastomosis procedure were reviewed. No follow-up was available in five patients; therefore, the basis of this report and its analysis was based on 200 consecutive procedures in which at least two of the three surgeons participated. Particular emphasis was placed on continence, particularly nighttime continence. The incidence of pouchitis, either a single episode or intermittent episodes, was surveyed. Particular attention was paid to the level of rectal mucosectomy and anastomosis at the top of the columns of Morgagni, thus retaining the transitional zone. RESULTS: Only 5% of patients were incontinent in the absence of pouchitis. Twenty-five patients (13%) wore a pad at night, but only nine (5%) wore a pad during the day. Of those patients with pouchitis, 6% (12) have had a single episode and 12% (23) were intermittently on medication. Therapy of pouchitis was usually carried out with ciprofloxacin 500 mg by mouth everyday or twice a day. CONCLUSIONS: Ileal pouch-anal anastomosis is an excellent procedure, provided technical details are adhered to. Satisfactory outcome with respect to nighttime continence can be achieved with rectal mucosectomy with minimal manipulation and retaining the transitional epithelium, performing the pouch anastomosis at the top of the columns of Morgagni. The incidence of pouchitis is disappointing but need not be inhibiting of either patients or carrying out this life-saving procedure in patients with ulcerative colitis and familial polyposis.

Pathogenesis, prevention, and management of catheter-associated infections.

Infection of vascular catheters is one of the leading causes of nosocomial bacteremia in the critically ill patient. Most catheter-associated infections result from exogenous microbial contamination of the catheter at the time of insertion or during use and are endemic. Prevention of catheter-associated infection is based on measures designed to eliminate the potential for microbial contamination of the skin at the catheter insertion site, the catheter hub, tubing connectors, and any inline devices that may be present. Development and implementation of catheter-care protocols for use in the ICU should be effective in preventing catheter infections. The diagnosis of catheter infections is difficult, as there are few signs or symptoms that are specific for an infected catheter. Catheter infection should be suspected in patients who develop fever, chills, and leukocytosis with no other apparent site of infection.

Comparison of empiric aztreonam and aminoglycoside regimens in the treatment of serious gram-negative lower respiratory infections.

An open-label, controlled, randomized study was performed to assess the efficacy and safety of combination regimens using either aztreonam or an aminoglycoside control regimen as empiric therapy for suspected aerobic gram-negative bacillary pneumonia or purulent bronchitis. Eighty-four patients, 42 in each arm of the study, were randomly assigned to one of two treatment regimens. The combination aztreonam regimen included aztreonam, 2 gm every 8 hours (q8h), plus either clindamycin, 600 to 900 mg q8h, or nafcillin, 1.5 gm to 2 gm every 6 hours (q6h). The control regimen was one of the following depending on the combination therapy that was designated standard at each of the three study institutions: amikacin, 5 mg/kg q8h, plus cefazolin, 1 gm q8h; amikacin, 500 mg every 12 hours plus mezlocillin, 4 gm q6h; or kinetically dosed tobramycin plus ticarcillin, 3 gm to 4 gm q4h. The two groups were well matched in terms of demographics and clinical characteristics. Among the 84 patients, organisms from the Enterobacteriaceae family accounted for the largest proportion of isolates (44%) including Escherichia coli (13%), Klebsiella species (14%), and Serratia species (9%). Other commonly identified organisms were Pseudomonas aeruginosa (19%), Haemophilus influenzae (15%), Streptococcus pneumoniae (12%), and Staphylococcus aureus (8%). Results of this trial included clinical response rates of 83% in both groups (P = 0.951) and a microbiologic cure rate of 75% in the aztreonam group and 63% in the control group (P = 0.291). In the 59 patients with documented aerobic gram-negative pneumonia, microbiologic eradication rates were 72% in the aztreonam group versus 57% in the control group (P = 0.359). Duration of treatment tended to be shorter in the aztreonam group than in the control group, with a median 10 days of therapy versus 12 days of therapy (P = 0.095), respectively. In addition, the percentage of patients requiring nonstudy antimicrobial agents tended to be lower in the aztreonam group than the control group, involving 21% of patients in the aztreonam group compared with 36% of patients in the control group (P = 0.086). All regimens were well tolerated, and no patient was withdrawn because of adverse reactions to the study medications. Two patients, both in the control group, required dose reduction, which was necessitated by possible aminoglycoside-induced nephrotoxicity. This trial shows that aztreonam is an effective agent with an excellent safety profile when used in combination regimens for the empiric treatment of pneumonia. A well-controlled trial is needed to verify the trend toward shorter hospital stays and a reduced need for additional antimicrobial agents seen with the aztreonam regimen when compared with those receiving aminoglycoside-combination regimens.

Circulating factors contribute to elevation of intracellular cyclic-3',5'-adenosine monophosphate and depression of superoxide anion production in polymorphonuclear leukocytes following thermal injury.

We have previously demonstrated that bactericidal activity and superoxide anion (O2-) production are depressed concomitantly in polymorphonuclear leukocytes (PMNs) following thermal injury in a guinea pig model, and the bactericidal defect is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate (cAMP). The purpose of the present investigation was to determine the relationship between elevation of intracellular cAMP and depression of O2- production in PMNs following thermal injury and determine the involvement of circulating factors in the development of these alterations. The kinetics of O2- production and dose responses to formylmethionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA) were depressed in peripheral PMNs following thermal injury in this experimental model. Sera obtained during the period of PMN dysfunction induced depression of O2- production in response to fMLP and elevation of intracellular cAMP in normal PMNs. Pretreatment of normal PMNs with nonsteroidal anti-inflammatory drugs (NSAID; indomethacin or piroxicam) inhibited the elevation of intracellular cAMP mediated by sera from the injured animals but had no effect on the depression of O2- production observed under similar conditions. Treatment of PMNs from injured animals with NSAID under conditions known to reduce the cAMP content of the cells and correct the bactericidal defect did not normalize O2- production. Studies utilizing sera from two thermally injured patients confirmed findings in the guinea pig model of serum-mediated elevation of intracellular cAMP and depression of O2- production in normal PMNs and effects observed with NSAID. These results suggest that circulating factors contribute to the elevation of intracellular cAMP and depression of O2- production in PMNs following thermal injury. Whereas the increase in intracellular cAMP may be involved in the depression of O2- production, our results suggest that there is not a direct link between these alterations.

Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement.

Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin-clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third-generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable.

Bactericidal defect of neutrophils in a guinea pig model of thermal injury is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate.

PG of the E series inhibit major effector functions of polymorphonuclear leukocytes (PMN) by elevating intracellular cAMP. The present study investigated the involvement of this mechanism in the bactericidal defect of PMN induced by thermal injury in a guinea pig model. Peripheral and peritoneal exudate PMN harvested from thermally injured guinea pigs at 1 or 2 days postburn had decreased bactericidal activity against Pseudomonas aeruginosa and a marked increase in cAMP content. Production of PGE1 by these cells in the absence of exogenous PMN activators was also increased. Treatment of PMN in vitro or in vivo with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, and piroxicam) restored bactericidal activity to normal and concomitantly reduced cAMP content and PGE1 production. A concomitant reduction in cAMP content and PGE1 production was also observed as bactericidal activity of PMN returned to normal under natural conditions during 4 to 7 days postburn. The enhancement of PMN bactericidal activity mediated by NSAID was fully counteracted by purified PGE1, theophylline, and by cAMP itself. These results suggest that the bactericidal defect of PMN induced by thermal injury is related to elevation of cAMP and that PGE1 plays a significant role in this phenomenon.

Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats.

Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonsteroidal anti-inflammatory drugs correct the bactericidal defect of polymorphonuclear leukocytes in a guinea pig model of thermal injury.

We conducted studies to determine the effects of parenteral therapy with indomethacin, ibuprofen, and piroxicam on key immunologic and hematologic alterations induced by thermal injury. Drugs (10-20 mg/kg) or placebo were administered intramuscularly to thermally injured guinea pigs at 3 h postburn and then daily for nine days postburn. All three drugs inhibited production of 6-keto prostaglandin F1 alpha and thromboxane B2 in wound fluid and concomitantly restored the bactericidal activity of polymorphonuclear leukocytes (PMNLs) against Pseudomonas aeruginosa to normal. Indomethacin also increased the proliferative response of splenic lymphocytes to concanavalin A; however, ibuprofen and piroxicam had no effect on this response. None of the drugs affected the extent of systemic complement consumption, thrombocytopenia, leukocytosis, or leukopenia in the injured animals. These results suggest that the PMNL bactericidal defect induced by thermal injury is preventable or reversible and that the mechanisms responsible for this defect are inhibitable by nonsteroidal anti-inflammatory drugs.

Bacterial infectibility of chronically implanted endothelial cell-seeded expanded polytetrafluoroethylene vascular grafts.

Vascular prosthetic grafts become more resistant to infection as the interval between implantation and bacteremic challenge increases. Endothelial cell (EC) seeding of such grafts has been shown to improve measurably their ability to resist a bacteremic challenge several weeks after implantation, presumably by reducing the amount of thrombus-free area (TFA) on their luminal surface. However, no investigators have reported the impact of EC seeding on the ability of chronically implanted vascular prostheses to resist a late bacteremic challenge. Bilateral common carotid interposition grafts were placed in 15 adult mongrel dogs with a 4 mm internal diameter, experimental, expanded polytetrafluoroethylene (ePTFE) prosthesis. One animal died shortly after operation and the grafts in two dogs thrombosed, thereby leaving 12 animals with at least one patent graft for subsequent study. At a mean interval of 45 weeks after implantation, five dogs (seven patent grafts) were challenged with an intravenous infusion of 3 X 10(8) radiolabeled Staphylococcus aureus; bacterial adherence and the TFA of the graft's luminal surface were determined for each of the patent grafts. There was no statistically significant difference in bacterial adherence or TFA between EC-seeded and control grafts. At a mean interval of 53 weeks after implantation, the remaining seven dogs (14 patent grafts) received a similar bacterial infusion and the animals were allowed to recover. Five days later, the grafts were harvested and cultured. Once again, there was no significant difference in the infectibility of EC-seeded vs. control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Opsonization of bacteroides by the alternative complement pathway reconstructed from isolated plasma proteins.

Opsonization of clinical isolates of B. fragilis and B. thetaiotaomicron with the six isolated proteins of the alternative complement pathway under physiological conditions resulted in considerable C3 deposition on the bacterial surfaces. The time course of C3 deposition was similar to that observed in EGTA-serum; however, the magnitude of C3 deposition was twofold greater in EGTA-serum. Opsonization of the bacteria with the isolated alternative pathway proteins failed to promote adherence, uptake, or killing by polymorphonuclear leukocytes, whereas opsonization of the bacteria with EGTA-serum facilitated these events. The difference in opsonic capacity of isolated proteins and EGTA-serum was not related to the quantitative difference in C3 deposition, because repeated opsonization of the bacteria with isolated proteins resulting in C3 deposition comparable to that observed in EGTA-serum only minimally increased adherence of the bacteria to polymorphonuclear leukocytes. SDS-PAGE and autoradiographic analysis of C3 extracted from bacteria opsonized with isolated proteins or EGTA-serum using methylamine and SDS demonstrated that the predominant form of C3 bound by ester bonds under both sets of conditions was iC3b. A low molecular weight C3 cleavage fragment was detected in extracts from bacteria opsonized with isolated proteins, but it accounted for only a minor fraction of the bound C3. The results of our study demonstrate that the early phase of opsonization involving activation of the alternative pathway by B. fragilis and B. thetaiotaomicron and resultant C3 deposition on the bacterial surfaces does not require auxiliary serum factors, but the effector phase of opsonization of these bacteria involving recognition of bacteria-bound C3 by polymorphonuclear leukocytes and the induction of phagocytosis and intracellular killing is dependent on such factors. Natural IgM antibodies serve as auxiliary factors is opsonization of B. thetaiotaomicron by the alternative pathway, whereas additional serum factors are required for alternative pathway-mediated opsonization of B. fragilis.

The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat.

It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.

Temporal relationships among immunologic alterations in a guinea pig model of thermal injury.

Temporal relationships among various humoral and cellular alterations of host defense mechanisms were investigated in a guinea pig model of thermal injury during three weeks after burning. Reduction in serum concentration of C3 and fixation of C3 on Pseudomonas aeruginosa, presence of activated C3 in plasma, and elevations in levels of 6-ketoprostaglandin F1 alpha and thromboxane B2 in wound fluid were observed at 3-6 hr after burning. These alterations were accompanied by reduction in intrinsic bactericidal activity of polymorphonuclear neutrophils (PMNs) against P. aeruginosa, suppression of bactericidal activity of PMNs by serum, and decreased blood clearance of P. aeruginosa. All parameters returned to normal values by seven to nine days after burning. Proliferative responses of splenic lymphocytes to T cell mitogens were depressed at four days after burning and were maximally reduced at eight days. These data support the concept that there is a continuum of immunologic alterations resulting from thermal injury and that consumption of complement and increase in arachidonic acid metabolism are early events.

Liver resection. A comparison using the Nd-YAG laser, an ultrasonic surgical aspirator, or blunt dissection.

Before gaining wide acceptance, possible surgical tools should be compared with the standard ones. This study, therefore, compared the Nd-YAG laser and the CUSA with the standard blunt dissection technique for liver resection in 24 dogs (8 in each group). Using a noncontact technique, the Nd-YAG laser was used for cutting as well as coagulation. The Nd-YAG laser or the CUSA reduced the resection time, with the laser being the faster of the two, and was accompanied by a probable but not significant decrease in perioperative blood loss. The CUSA delineated the blood vessels and bile ducts and gave superior control. It also caused significantly less tissue damage on light and electron microscopic examination than the other two methods. Cultures taken 1 week after operation showed that the risk of bacterial infection correlated well with the extent of tissue necrosis and was significantly greater after use of the Nd-YAG laser than after use of the CUSA. The numbers of animals are small and the conclusions should be tempered by caution, but it appears that the CUSA, but not the Nd-YAG laser, may improve the results of elective liver resection.

Effect of Intralipid on clearance and organ uptake of bacteria in intra-abdominal sepsis in rats.

Although infusion of Intralipid has been reported to block reticuloendothelial system (RES) function, it is unclear if this is true at rates used clinically. This study investigates the effect of Intralipid, infused at a rate providing about half of the non-protein caloric needs, on survival and bacterial clearance in septic rats. Continuous infusion of Intralipid (0.9 g/100 g bw/d) or saline (controls) was started immediately after induction of hyperdynamic intra-abdominal sepsis (bacterial agents: E. coli, B. thetaiotamicron). RES function was studied by means of intravenous injection of Selenium-labelled, viable E. coli after 24 or 48 h. Compared to the saline-treated controls, Intralipid did not cause any change in clearance from blood or localisation to liver, spleen or lungs. The 24 and 48 h survival rates were about 80 and 65%, respectively, and similar in the two groups. It is concluded that infusion of Intralipid at a rate close to that used clinically did not impair survival or bacterial clearance in rats with gram-negative sepsis.