Bacterial infections as complications of dog bites]

Dog bites may result in serious bacterial infections with e.g. the gram-negative rods Capnocytophaga canimorsus and Pasteurella multocida. Human disease caused by these microorganisms can be complicated by acute development of septicaemia and/or meningitis followed by disseminated intravascular coagulation syndrome, peripheral gangrene and renal failure. The mortality of C. canimorsus septicaemia is about 23-31%. These severe infections are most often reported in immunocompromised patients and occur a few days after the bite. By reviewing the literature it is concluded that the broadest prophylactic coverage is obtained by amoxicillin/clavulanic acid and that antibiotic prophylaxis should be given to all immunocompromised patients experiencing a dog bite. Moreover, prophylactic treatment should be initiated for all patients with greater penetrating wounds and those involving the hands.     

Postsplenectomy Capnocytophaga canimorsus sepsis presenting as an acute abdomen

Patients with intra-abdominal processes that require prompt surgical intervention, including appendicitis, perforated viscus, ischemic bowel, volvulus, and bowel obstruction, often present with signs and symptoms of an acute abdomen. Several medical problems can mimic an acute abdomen. Overwhelming postsplenectomy infection is a life-threatening condition that can present with acute abdominal symptoms. The incidence of overwhelming postsplenectomy infection ranges from 1% to 25%, and is caused by Streptococcus pneumoniae in 50% of cases. Capnocytophaga canimorsus, a bacteria commonly found in dog saliva, accounts for less than 1% of cases. Overwhelming postsplenectomy infection has a rapidly deteriorating course that progresses to respiratory and renal failure, cardiovascular collapse, and death. The mortality associated with overwhelming postsplenectomy infection is 60% to 80%. Early diagnosis and institution of appropriate antibiotic therapy and supportive care is essential to improve patient outcome. A previously healthy woman who had undergone splenectomy secondary to trauma 11 years earlier presented with symptoms of an acute abdomen. A diagnosis of overwhelming postsplenectomy infection due to C canimorsus was made based on her peripheral blood smear and blood culture findings. Early aggressive care and antibiotic treatment resulted in a successful outcome for this patient with no long-term morbidity. This patient's clinical course demonstrates the importance of early diagnosis and treatment of overwhelming postsplenectomy infection.     

Elevated methemoglobin in patients with sepsis

BACKGROUND: It has been reported that large amounts of nitric oxide (NO) are released in patients with sepsis. NO is converted to methemoglobin and nitrate. This study was designed to determine whether blood methemoglobin levels were increased in patients with sepsis or septic shock. METHODS: Forty-five critically ill patients including 8 with sepsis but without shock, 6 with septic shock and 31 non-septic patients were enrolled in the study. For septic and septic shock patients, blood methemoglobin concentrations were measured during sepsis or septic shock and at the time of recovery or just before the onset of sepsis. For the remaining non-septic patients, methemoglobin concentrations were measured at ICU admission and discharge. RESULTS: Blood methemoglobin levels in the presence of sepsis or septic shock were significantly (P < 0.05) higher than those in non-septic patients and those at recovery or just before the onset of sepsis in both septic and septic shock patients. CONCLUSIONS: Blood methemoglobin concentration may be useful as a marker of the onset of sepsis or septic shock.     

Enteral feeding intolerance: an indicator of sepsis-associated mortality in burned children

OBJECTIVE: To determine if enteral feeding intolerance (EFI) is associated with sepsis and increased mortality in children with severe burns. DESIGN: A survey. SETTING: A pediatric burn unit. PATIENTS: Ninety-one children surviving longer than 5 days with greater than 80% total body surface area burns. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Enteral feeding intolerance indicated by high gastric residuals (> 150 mL/h) or uncontrollable diarrhea (> 2500 mL/d); thrombocytopenia (platelet count < 100 x 10(9)/L); hyperglycemia (glucose level > 11.1 mmol/L [> 200 mg/dL]); sepsis (pathogenic bacteremia or fungemia noted on blood culture results); and mortality. RESULTS: Neither EFI nor sepsis developed in 71 patients, EFI alone developed in 2 patients, sepsis alone developed in 5 patients, and EFI and sepsis developed in 13 patients. Enteral feeding intolerance and sepsis were associated by contingency table analysis (P<.001). Mortality was 8% (6 patients) in those with neither EFI nor sepsis, 50% (1 patient) in those with EFI alone, 60% (3 patients) in those with sepsis alone, and 77% (10 patients) in those with EFI-associated sepsis. The 2 latter groups were different from the group with neither EFI nor sepsis (P<.05). Enteral feeding intolerance was identified in 70% of patients before sepsis; thrombocytopenia, 64%; and hyperglycemia, 66%. When compared with thrombocytopenia and hyperthermia, no variables were found to be superior to others for predicting sepsis. CONCLUSIONS: Enteral feeding intolerance was associated with the development of sepsis and increased mortality in children with greater than 80% total body surface area burns. This sign was identified in 70% of the cases before pathogens were found in the blood; no difference could be shown between the identification of EFI, thrombocytopenia, and hyperglycemia before sepsis. These data indicate that the development of EFI should be used as an indicator of infection and should prompt a search for an inciting focus.     

The sepsis syndrome in a Dutch university hospital. Clinical observations

BACKGROUND: Most studies of the cause of sepsis syndrome focus on patients hospitalized in intensive care units. In this study, we analyzed the incidence, cause, and outcome of the sepsis syndrome in all hospitalized patients. METHODS: Clinical and microbiologic data were obtained for 382 patients (5.6% of all patients admitted) from whom blood was drawn for culture. RESULTS: The incidence of the sepsis syndrome was 13.6 per 1000 patients admitted (1.06 per 1000 hospital days), while the incidence of septic shock was 4.6 per 1000. The respiratory tract was the predominant infection site. Of all patients with sepsis syndrome, 38% (n = 35) had positive blood cultures. More than half of these cultures (13 [57%]) were caused by gram-positive microorganisms (excluding patients receiving selective decontamination of the digestive tract and those with intravascular device-related bacteremias). The mortality for patients with sepsis syndrome without shock was 28% (17/61), while for patients with septic shock, it was 55% (17/31). Patients with cardiovascular diseases had a significantly (P < .005) greater risk of dying during a sepsis syndrome episode than patients with other predisposing factors. Multivariate analysis of factors influencing outcome identified the development of shock and an immunocompromised state as being significantly associated with outcome in patients with sepsis syndrome. CONCLUSIONS: Patients fulfilling the criteria for the sepsis syndrome are at great risk of developing septic shock or multiple-organ failure and subsequently dying. In our hospital, the majority of bacteremic episodes were associated with gram-positive microorganisms.     

Early-response cytokine expression in adult middle ear effusions

We determined the diseases associated with extremely high levels of alkaline phosphatase in hospitalized patients. Computerized laboratory records of the Hospital of Saint Raphael identified all inpatients who had elevations of alkaline phosphatase above 1,000 U/l from April 1994 to September 1995. Thirty-seven inpatients with alkaline phosphatase levels above 1,000 U/l were identified. Six had bone involvement from malignancy or Paget's disease and were eliminated from further analysis, and 31 patients were included in the study. Levels of alkaline phosphatase ranged from 1,014 to 3,360 U/l. Ten patients had sepsis as the cause of the elevated alkaline phosphatase. These included gram-negative organisms, gram-positive organisms, and two patients with fungal sepsis. Seven of 10 patients with sepsis had an extremely high alkaline phosphatase level and a normal bilirubin, 3 of 10 patients with sepsis also had acquired immunodeficiency syndrome (AIDS). Eight patients had biliary obstruction, 7 with malignant obstruction and 1 with a common bile duct stone. Nine patients had AIDS. The cause of the elevated alkaline phosphatase in these included three with sepsis, three with mycobacterium avium intracellulare (MAI) infection, two with cytomegalovirus infection, and one with Dilantin toxicity. Three patients had diffuse liver metastases. Finally, four patients had benign intrahepatic disease, including one patient with liver hemangiomas, one patient with sarcoid hepatitis, one patient with lead toxicity, and one patient with drug-induced cholestasis. Extremely high elevations of alkaline phosphatase are most frequently seen in patients with sepsis, malignant obstruction, and AIDS. Patients with sepsis can have an extremely high alkaline phosphatase level and a normal bilirubin. A variety of other causes were also noted.     

Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production

IL-12 is a potent immunoregulatory cytokine that is essential for the development of protective immunity, as demonstrated by numerous animal models of infection. Here, we provide evidence for a critical role of IL-12 in human sepsis. The results of a prospective study of 184 patients undergoing major elective surgery of the upper and lower gastrointestinal tract revealed that, in contrast to patients showing uneventful recovery, monocyte IL-12 production was severely and selectively impaired in patients developing postoperative sepsis. Moreover, the extent of monocyte IL-12 suppression correlated with the severity of postoperative sepsis. Monocyte IL-12 secretion was suppressed before surgery and remained low until the onset of sepsis. Therefore, the suppression of IL-12 secretion preceded the onset of postoperative sepsis but did not occur as a consequence of major surgery. In contrast, IL-1beta production was only reduced during the late postoperative course in patients developing postoperative sepsis, and TNF-alpha release was even increased at different time intervals before the onset of sepsis. Thus, reduced IL-12 release does not reflect a general defect in monocyte cytokine production. Consequently, these results establish a critical role for IL-12 in early resistance to postoperative infection and may allow for the development of novel therapeutic strategies designed to stimulate host defense mechanisms and to reduce the incidence and severity of septic complications.     

Bacteremia and fungemia in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan

To understand the etiology and clinical outcome of bacterial and fungal sepsis in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan, we conducted a prospective study of nonmycobacterial bacteremia and fungemia in HIV-infected patients with fever who were admitted to a university hospital in Taiwan during a 42-month period. Of 210 patients, 41 (19.5%) had a total of 52 episodes of sepsis due to nonmycobacterial bacteria or fungi, or both (15.5% of 336 episodes of fever). All but one patient had acquired immunodeficiency syndrome (AIDS), and the mean CD4 lymphocyte count was 29/microL (range, 0-321/microL). A total of 57 pathogens (39 bacteria and 18 fungi) were isolated from blood; polymicrobial sepsis due to both bacteria and fungi occurred in four episodes. Nontyphoid Salmonella (NTS) was the most common cause of community-acquired bacteremia (24/30, 80%). Staphylococcus aureus bacteremia was diagnosed in three episodes while Streptococcus pneumoniae bacteremia was found in only one. Cryptococcus neoformans was the most common cause of fungemia and was responsible for 12 episodes, while fungemia due to Penicillium marneffei and Histoplasma capsulatum, two emerging fungi in Taiwan, were diagnosed in four cases and one case, respectively. Nine episodes, eight of bacteremia and one of candidemia, were nosocomial. The overall in-hospital mortality was 29%, and nosocomial sepsis was associated with a higher mortality rate (56%, p = 0.02). The mean duration of survival after recovery from initial sepsis was 426 days. We conclude that NTS bacteremia was the most common cause of sepsis in patients with advanced HIV infection in Taiwan and clinicians caring for such patients should watch for emerging fungal infections. Nosocomial sepsis was associated with a high mortality rate. The mean survival duration after recovery from sepsis of our patients was short.     

Purpura fulminans in pneumococcal sepsis: case report and review

Purpura fulminans is classically defined by ecchymotic skin lesions, fever, and hypotension. The majority of cases occur in association with bacterial sepsis, and disseminated intravascular coagulation (DIC) is usually present. Prompted by our experience with a patient with pneumococcal sepsis and purpura fulminans in whom hypotension was never observed, we evaluated the important parameters of sepsis in reports of this syndrome. 42 additional cases of pneumococcal bacteremia and purpura fulminans were identified. Hypotension was present in only 51%. Although DIC was present in 85% of patients, hypofibrinogenemia was documented in only 26%. By contrast, both hypotension and hypofibrinogenemia are present in the vast majority of patients described with purpura fulminans in association with meningococcal sepsis. These data confirm that hypotension is not a necessary feature of the syndrome of purpura fulminans associated with pneumococcal sepsis and suggest further that qualitative or quantitative differences exist in the DIC cascade of pneumococcal vs meningococcal sepsis.     

The hemodynamic derangements in sepsis: implications for treatment strategies

The incidence of the sepsis syndrome has increased dramatically in the last few decades. During this time, we have gained new insights into the pathophysiologic mechanisms leading to organ dysfunction in this syndrome. Yet, despite this increased knowledge and the use of novel therapeutic approaches, the mortality associated with the sepsis syndrome has remained between 30% and 40%. Appropriate antibiotic selection and hemodynamic support remain the cornerstone of treatment of patients with sepsis. Recent studies have failed to demonstrate a global oxygen debt in patients with sepsis. Furthermore, therapy aimed at increasing systemic oxygen delivery has failed to consistently improve patient outcome. The primary aim of the initial phase of resuscitation is to restore an adequate tissue perfusion pressure. Aggressive volume resuscitation is considered the best initial therapy for the cardiovascular instability of sepsis. Vasoactive agents are required in patients who remain hemodynamically unstable or have evidence of tissue hypoxia after adequate volume resuscitation.     

Long-term evaluation of hip arthroplasty in patients with an ipsilateral knee arthrodesis

Hip arthroplasty with an ipsilateral knee arthrodesis occurs infrequently but does raise concern regarding surgical technical difficulties, dislocation, sepsis, and long-term loosening. Sixteen patients were evaluated 7.5 years (average period) after surgery. Technical difficulties were not prohibitive. No dislocation or revision was necessary in any of the cases. Two patients died as a result of unrelated sepsis from an infected knee. Loosening and protrusio of the acetabulum occurred in two patients. Hip arthroplasty in patients with a fused knee does not incur undue risk of loosening or instability and can provide long-term good function and pain relief. Patients with multiple joint arthroplasties, in whom concurrent sepsis occurs, can have devastating results.     

The presence of wild-type TP53 is necessary for the radioprotective effect of the Bowman-Birk proteinase inhibitor in normal fibroblasts

This paper uses definitions of a consensus conference (ACCP/CCM) describing the epidemiology of SIRS, sepsis and septic shock in surgical ICU patients. During a period of 2 years a total of 656 patients were prospectively enrolled into the study. 335 patients (51.1% of the total population) developed SIRS (systemic inflammatory response syndrome); in 65 of these patients infection could be documented, i.e. they met the criteria of sepsis, 47 of these 65 septic patients developed septic shock, with mortality of 53.2%. SIRS is associated with a high sensitivity but a low specificity in predicting the outcome of ICU patients. Moreover, SIRS and sepsis appear to be of minor clinical relevance. On the contrary, septic shock describes a very high risk group of patients which should be characterized more closely in future studies.     

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors unmask cryptic regulatory mechanisms

Plasma concentrations of soluble interleukin (IL)-1 receptor type II, IL-10, and IL-13 were measured in 42 patients with clinically defined sepsis during a 3-day follow-up and in 7 healthy humans after intravenous injection of endotoxin (2 ng/kg). Levels of soluble IL-1 receptor type II were persistently elevated in patients with sepsis than in healthy controls and higher in nonsurviving patients (n = 22) than in surviving patients (n = 20) at all time points. IL-10 was found in the circulation of 81% of patients with sepsis, while it was not detectable in normal plasma. During follow-up, IL-10 remained invariably high only in nonsurviving patients, while it significantly decreased in survivors. Endotoxin induced IL-10, while soluble IL-1 receptor type II remained unchanged. IL-13 remained undetectable in the vast majority of patients and was not induced by endotoxin. Enhanced IL-13 production does not seem to be part of an inducible host defense mechanism during sepsis.     

Severe depression of gut absorptive capacity in patients following trauma or sepsis

Although clinical studies suggest enteral, as opposed to parenteral, feeding lowers morbidity and mortality rates following severe trauma and after sepsis, it is unknown whether gut absorptive capacity (GAC) is indeed maintained under such conditions. To study this, GAC was determined in patients with blunt trauma (n = 8) and with sepsis (n = 11) by the 1-hour D-xylose absorption test. Excluded were patients with ileus, nasogastric output of more than 600 mL/24 hours, or residual gastric content of more than 25 mL after the D-xylose test. Trauma patients (ISS 8-14) and patients with intra-abdominal sepsis had an initial D-xylose test within 24 to 48 hours of admission, at 72 to 96 hours, and then weekly until D-xylose absorption had returned to normal. D-xylose (25 g in 200 mL water) was given via nasogastric tube to patients and orally to healthy volunteers (controls: n = 8). Results show that GAC was depressed at 24 to 96 hours in both groups but returned to normal by 1 to 3 weeks after trauma or resolution of sepsis. Thus (1) gut absorptive capacity was severely depressed early after trauma and after the onset of sepsis; and (2) the 1-hour D-xylose absorption test provided a simple, quantitative assessment of GAC in critically ill patients. Hence, therapeutic agents that restore gut absorptive capacity may be useful for further reducing morbidity and mortality rates following trauma or the onset of sepsis.     

Potentiation of morphine-induced seizure by 6-hydroxydopamine

A retrospective study of sixteen patients with pelvic fractures compounded through the perineum, rectum, or vagina showed a mortality of 50 per cent. The cause of death in seven of the eight patients was sepsis and multisystem failure. The initial surgical management of these patients must include complete diversion of the fecal stream so that pelvic and systemic sepsis may be prevented.     

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock

OBJECTIVES: To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS: We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.     

The circulating adhesion molecules sICAM-1 and sP-selectin in patients with sepsis

AIM: The aim of this study was to investigate whether the plasma levels of the circulating adhesion molecules sICAM-1 and sE-selectin could serve as early predictors of developing sepsis and its severity. METHODS: Twenty-four patients admitted to an intensive care unit with a high risk of developing septic complications were enrolled in this study. Patients were divided into three groups: group I, with infection without systemic sepsis, n = 8; group II, surviving patients with severe sepsis and multi-organ failure (MOF), n = 8; and group III, nonsurviving patients with severe sepsis and MOF, n = 8. Classification of patients was performed according to the clinical criteria defined by the Sepsis Consensus Conference in 1992. Blood samples were taken at 7 a.m. starting from the day of admission until the 7th day after diagnosis of sepsis. Plasma levels of sICAM-1 and sE-selectin were determined in all samples taken between the 3rd pre-septic day and the 7th day after the diagnosis of sepsis was made. RESULTS: In group I, both sICAM-1 (354.21 +/- 128.60 ng/ml, 86 samples) and sE-selectin (30.41 +/- 7.20 ng/ml, 86 samples) levels remained within the reference range over the whole period of observation. The sICAM-1 levels of group II (between 550.82 +/- 275.67 ng/ml and 445.08 +/- 243.63 ng/ml) tended to show values above the reference range without being significant. Mean sICAM-1 levels in group II did not differ from those of group I. From the 2nd pre-septic day onwards the sICAM-1 levels of group III increased, but not significantly. Significant differences in sICAM-1 levels between group I and group III were observed, with peaks at the samples of the 2nd preseptic day and after the 3rd day of sepsis, respectively (P < 0.05). The sE-selectin levels in group II were elevated from the 3rd preseptic day onwards, with a peak value on the 2nd day of sepsis (P < 0.05). Afterwards, levels decreased to initial values despite ongoing sepsis. Mean values of sE-selectin levels of group I and II were significantly different with the onset of sepsis (P < 0.05). Plasma levels of sE-selectin in group III were significantly elevated (66.30 +/- 9.00 ng/ml on the 3rd pre-septic day), reaching their maximal values of 106.67 +/- 21.66 ng/ml at the end of the observation period. Significant differences between sE-selectin levels of groups I and III existed from the 3rd pre-septic day onwards, and between group II and III on the 7th and 8th day of sepsis. CONCLUSION: Our results show that sICAM-1 is a relatively non-specific indicator for sepsis. In contrast, sE-selectin seems to be a good and early predictor of the beginning of severe sepsis with MOF. Furthermore, sE-selectin levels seem to have a prognostic value for the severity, possible course, and outcome of developing sepsis.     

Kids count--a children''s rights project

Offers a protocol of antibacterial therapy of abdominal sepsis in surgical patients. Analyzes the principal etiological agents of abdominal septic complications. Presents optimal schemes of antibacterial therapy of abdominal sepsis. Pays special attention to choice of antibiotics in different clinical situations.     

Epidemiology of sepsis and multiple organ dysfunction syndrome in children

STUDY OBJECTIVES: To determine the cumulated incidence and the density of incidence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS) in critically ill children; to distinguish patients with primary from those with secondary MODS. DESIGN: Prospective cohort study. SETTING: Pediatric ICU of a university hospital. PATIENTS: One thousand fifty-eight consecutive hospital admissions. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: SIRS occurred in 82% (n=869) of hospital admissions, 23% (n=245) had sepsis, 4% (n=46) had severe sepsis, 2% (n=25) had septic shock; 16% (n=168) had primary MODS and 2% (n=23) had secondary MODS; 6% (n=68) of the study population died. The pediatric risk of mortality (PRISM) scores on the first day of admission to pediatric ICU were as follows: 3.9 +/- 3.6 (no SIRS), 7.0 +/- 7.0 (SIRS), 9.5 +/- 8.3 (sepsis), 8.8 +/- 7.8 (severe sepsis), 21.8 +/- 15.8 (septic shock); differences among groups (p=0.0001), all orthogonal comparisons, were significant (p<0.05), except for patients with severe sepsis. The observed mortality for the whole study population was also different according to the underlying diagnostic category (p=0.0001; p<0.05 for patients with SIRS and those with septic shock, compared with all groups). Among, patients with MODS, the difference in mortality between groups did not reach significance (p=0.057). Children with secondary MODS had a longer duration of organ dysfunction (p<0.0001), a longer stay in pediatric ICU after MODS diagnosis (p<0.0001), and a higher risk of mortality (odds ratio, 6.5 [2.7 to 15.9], p<0.0001) than patients with primary MODS. CONCLUSIONS: SIRS and sepsis occur frequently in critically ill children. The presence of SIRS, sepsis, or septic shock is associated with a distinct risk of mortality among critically ill children admitted to the pediatric ICU; more data are needed concerning children with MODS. Secondary MODS is much less common than primary MODS, but it is associated with an increased morbidity and mortality; we speculate that distinct pathophysiologic mechanisms are involved in these two conditions.     

Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis

Neutrophils (polymorphonuclear neutrophils; PMN) and a redundant system of chemotactic cytokines (chemokines) have been implicated in the pathogenesis of the acute respiratory distress syndrome in patients with sepsis. PMN express two cell surface receptors for the CXC chemokines, CXCR1 and CXCR2. We investigated the expression and function of these receptors in patients with severe sepsis. Compared with normal donors, CXCR2 surface expression was down-regulated by 50% on PMN from septic patients (p < 0.005), while CXCR1 expression persisted. In vitro migratory responses to the CXCR1 ligand, IL-8, were similar in PMN from septic patients and normal donors. By contrast, the migratory response to the CXCR2 ligands, epithelial cell-derived neutrophil activator (ENA-78) and the growth-related oncogene proteins, was markedly suppressed in PMN from septic patients (p < 0.05). Ab specific for CXCR1 blocked in vitro migration of PMN from septic patients to IL-8 (p < 0.05), but not to FMLP. Thus, functionally significant down-regulation of CXCR2 occurs on PMN in septic patients. We conclude that in a complex milieu of multiple CXC chemokines, CXCR1 functions as the single dominant CXC chemokine receptor in patients with sepsis. These observations offer a potential strategy for attenuating adverse inflammation in sepsis while preserving host defenses mediated by bacteria-derived peptides such as FMLP.