Gram-negative Bacillary Sepsis Research Articles

Immunotherapy of sepsis: flawed concept or faulty implementation?

Gram-negative bacillary sepsis is a leading cause of death among patients hospitalized in intensive care units. While initial clinical studies with the passive administration of anti-endotoxin core-glycolipid (CGL) antibodies for the treatment and prophylaxis of sepsis showed promising results, subsequent studies failed to show a consistent benefit. There appears to be a good correlation between anti-CGL antibody levels at the onset of sepsis and maintenance of antibody levels during sepsis with outcome. Previous clinical studies may have failed because insufficient amounts of antibody were administered early in the course of sepsis. Unlike the case with anti-CGL antibodies, polyvalent, hyperimmune type-specific antibody preparations may prevent the development of infections; however, these antibodies also must be provided in adequate amounts and in close proximity to infection in order to provide a beneficial effect. These pharmacokinetic requirements may limit the utility of passive immunotherapy for the prophylaxis of sepsis. Active immunization of acutely traumatized patients or of rats subsequently rendered neutropenic with cyclophosphamide induced high antibody levels for extended periods of time. Since trauma and other conditions are associated with a Th 2 response, these conditions may favor antibody formation following active immunization. Active immunization with both anti-CGL and/or polyvalent-specific vaccines for the prophylaxis of sepsis with passive supplementation at the onset of sepsis is an approach that merits further investigation.

Antibody immunotherapy of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis continues to represent a significant cause of morbidity and mortality in hospitalized patients. Currently available medical therapy (antimicrobial agents, hemodynamic monitoring, aggressive fluid resuscitation, and nutritional support) for this disease process has reduced but not eliminated the severe consequences that may ensue. Recent investigations have demonstrated the ability of antibody directed against gram-negative bacterial lipopolysaccharide (LPS or endotoxin) to afford protection during experimental gram-negative bacillary sepsis. The core LPS-lipid A portion of endotoxin represents a determinant shared by many common gram-negative microorganisms that is luxuriantly expressed on the cell surface of rough mutants of Escherichia coli and Salmonella minnesota. These organisms or the outer membrane LPS isolated from them thus represent suitable immunogens for the development of cross-protective antibody preparations. Large quantities of highly cross-reactive antibody may potentially be obtained from several sources: murine or human monoclonal antibodies, immunization of large animals or humans with subsequent plasmapharesis and antibody isolation, affinity purification of large amounts of normal antibody, and pooling of prescreened lots of normal animal or human antibody that react to a particular bacterial antigen.

Shock in children with gram-negative bacillary sepsis and Haemophilus influenzae type b sepsis.

To study the incidence of shock in children in association with gram-negative bacillary (GNB) sepsis and Haemophilus influenzae type b sepsis, we reviewed all episodes of septicemia with those organisms in a 10-month period. GNB were isolated from 10.95% and H. influenzae b from 13.8% of the patients whose blood cultures yielded bacteria. Shock occurred in 12.5% of patients with sepsis caused by GNB and in 10.3% of those with H. influenzae b sepsis. Shock occurred more frequently in patients with H. influenzae b sepsis with meningitis (20.6%) and more commonly in those who had GNB sepsis without meningeal involvement (11.4%). GNB sepsis was associated with severe shock and caused death of three of the four patients. Only one of the five patients with shock caused by H. influenzae b had severe shock and died. The good outcome of patients with sepsis and shock caused by H. influenzae may be related to the health status before illness and prompt appropriate antibiotic therapy.

Pneumocystis carinli Pneumonitis

In a sense, opportunistic infections may serve as diagnostic indicators of certain host defects or disease processes that diminish the immune response. The myriad microbes comprising the endogenous and exogenous flora of man are rarely a threat to the health of normal individuals. However, once integrity of the immune system is breeched by disease, such as a malignancy, the relatively avirulent microbes of the immediate environment may cause invasive disease, or latent endogenous organisms may cause active disease. Thus, the otherwise healthy person who acquires infections such as Gram-negative bacillary sepsis, candidiasis, aspergillosis, or disseminated cytomegalovirus disease must be thoroughly studied for an underlying disease process.

Significance of viral infections in severe combined immunodeficiency disease.

An analysis of a prospective study of viral infections in 12 patients with severe combined immunodeficiency is presented. Infections of viral etiology were common, with pulmonary and gastrointestinal infections being most frequent. Fourteen of 25 infections (56%) were nonsocomially acquired and 10 of 25 (40%) were community-acquired. The period of symptomatology and the duration of viral excretion were usually prolonged beyond those associated with disease in the general pediatric population. Pulmonary infections were associated with considerable morbidity and mortality. Gastrointestinal infections disrupted gastrointestinal function and possibly played a role in enteric Gram-negative bacillary sepsis. The inability of these patients to eradicate these viruses in the absence of immunologic reconstitution resulted in significant morbidity, often with a fatal outcome.

Gram-Negative Bacillary Sepsis Associated With Use of Lipid Emulsion in Parenteral Nutrition

The use of solutions for parenteral nutrition has greatly enhanced the management of medical and surgical disorders. Two general classes of solutions are employed: total parenteral nutrition solutions (TPN), containing a mixture of amino acids, glucose, electrolytes, and vitamins, and soybean oil emulsion (Intralipid). Both solutions have been shown to support the growth of bacteria and fungi. 1,2 Although sepsis is a recognized complication of the use of TPN solutions, 2 there have been no reports of infection with the use of lipid emulsion. We report two distinct episodes of lipid emulsion-associated sepsis with two different Gram-negative microorganisms in a chronically ill infant. Report of a Case .—An infant with complications resulting from a midgut volvulus required parenteral nutrition at 3½ months of age and a central venous catheter was inserted. Both glucose-amino acid (TPN) solution and lipid emulsion were administered via a Y configuration delivery system. A 0.22-μ particle

Septic Nonsuppurative Thrombophlebitis

To the Editor.—In a recent article, Septic Nonsuppurative Thrombophlebitis (Arch Surg111:122, 1976), Zinner and colleagues described 11 patients with cannula-associated Gram-negative bacillary sepsis refractory to cannula removal and antimicrobial therapy. Metal (scalp-vein) needles were implicated in seven cases. Clinical remission followed resection of mildly inflamed veins; in each case culture of the vein yielded the blood pathogen. The authors concluded that the thrombophlebitic veins constituted the source of persistent septicemia although no suppuration or organisms were identified histologically. This report appropriately re-emphasizes iatrogenic hazards of infusion therapy. However, we have reservations about the interpretation of data presented: Septicemia, and especially septic thrombophlebitis, arising from use of metal needles has been rare.1-33Only one case of needle-related septicemia was detected among 535 patients in five prospective studies. Moreover, prior to this series, a total of only five cases of needle-related septicemia had been reported2; one was linked to

Septic nonsuppurative thrombophlebitis.

Nonsuppurative peripheral thrombophlebitis is a frequently recognized source of sepsis. Eleven patients cared for on general medical and surgical services had Gram-negative bacillary sepsis on this basis. Ten had isolation of organisms of the Klebsiella-Enterobacter group from the involved peripheral vein. All failed to respond to organism-sensitive antibiotics until the involved vein was excised. After local vein excision, all patients were afebrile within 48 hours and recovered. In seven of the 11 patients, the septic phlebitis source was associated with a standard intravenous needle, and none had cutdown procedures. It is strongly emphasized that this condition is a source of life-threatening sepsis that can be treated by vein excision at the bedside. The treatment in our patients resulted in no morbidity. A high index of suspicion is necessary to diagnose this occult source of sepsis because of the minimal local physical signs.

Letter: The Limulus test and gram-negative bacillary sepsis.

Sir .—Concerning the article by Feldman and Pearson, which appeared in the August 1974 issue of theJournal(128-172, 1974), we agree with their final remark that the Limulus test must be better standardized, but it is our opinion and also that of others 1 that the Limulus assay is suitable in detecting endotoxemia due to Gram-negative bacteria. In our recent studies, we discovered in five of six cases of neonatal necrotizing enterocolitis a severe constant and fatal endotoxemia, employing lysates from different preparations. It is our opinion that endotoxemia plays a fundamental role in this condition.

The Limulus Test and Gram-Negative Bacillary Sepsis-Reply

Sir .—We agree that the Limulus assay is suitable for detecting endotoxemia, but contend that it is not of value in detecting Gram-negative bacillary sepsis or bacteremia. Only when the preparation and sensitivity of Limulus lysate and extraction procedure of endotoxin have been standardized can the clinical usefulness of this test be finally determined. Ultimately the physician will have to ask, Will this test assist me in determining the diagnosis and management of my patient's condition? If the number of false positives and false negatives is equal to or greater than the number of true positives or true negatives (based on culture-proved infections), then the test will offer no advantage over the present clinical and laboratory diagnosis of infection, and may indeed be another cost-accountable expense for the patient. To date, the published studies are only suggestive of clinical value of the assay. Further studies in large and high-risk populations

The Limulus test and gram-negative bacillary sepsis.

The diagnostic value of the generally accepted Limulus lysate endotoxin test was examined in a series of pediatric cancer patients having or suspected of having Gram-negative bacterial sepsis. One hundred fifty-four tests were performed, with simultaneous blood cultures available for 143 of these. Of the 28 patients with one or more separate episodes of Gram-negative bacillary bacteremia, only two had positive endotoxin tests. Eight children who died with Gram-negative septicemia within 24 hours after being tested for endotoxin had negative tests. These results, supported by others, indicate that the Limulus amebocyte lysate test is not clinically useful for detecting Gram-negative infections or predicting their outcome. Lack of standardized procedures for lysate preparation and endotoxin extraction from plasma could explain the current disagreement of published test results.

Bacteroidaceae bacteremia with disseminated intravascular coagulation

Three patients with Bacteroidaceae bacteremia and disseminated intravascular coagulation (DIC) are described. The association of DIC with this anaerobic infection has been infrequently reported. Septic shock due to Bacteroidaceae appears to involve endotoxin as in aerobic gram-negative bacillary sepsis. Similarly, endotoxin may be the trigger mechanism for initiating DIC in both aerobic and anaerobic gram-negative bacillary sepsis.

Bacteremic Bacteroides infections.

Thirty-nine patients with bacteremia due to anaerobic Gram-negative bacilli of the genus Bacteroides were seen in a general hospital during a 6-year period. Many of these infections occurred in patients postoperatively, particularly after trauma to the bowel or female pelvic organs. There was an impressive prevalence of malignant neoplasms, diabetes mellitus, and prior therapy with corticoids or multiple antimicrobials. The Bacteroides strains isolated tended to be resistant to the bacteriocidal antibiotics used for treating Gram-negative bacillary sepsis (penicillin, cephalothin, kanamycin, and Colistin). Ten strains were resistant to tetracycline, a drug widely recommended for bacteroides infections. Of 38 isolates tested all were susceptible to chloramphenicol. Diagnosis of bacteroides sepsis demands a high index of suspicion and routine use of anaerobic cultures. Successful therapy depends on early surgical debridement and institution of appropriate antibiotics. In the absence of sensitivity data bacteroides sepsis appears to represent another of the few indications for therapy with chloramphenicol.