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Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies.

Between 1976 and 1982, Enterobacteriaceae and Pseudomonas aeruginosa were prospectively counted in fecal specimens from leukemic patients with gram-negative bacteremia. The strains isolated from the blood and feces of 55 patients were compared. Translocation of the dominant fecal strain of Enterobacteriaceae or P. aeruginosa was observed in 45 cases (82%) and was strongly associated with granulocytopenia of less than 10(2) cells/microliter (P less than .0001). Thirteen (81%) of 16 patients with bacteremia caused by P. aeruginosa were intestinal carriers of the same strain, whereas only 2 (5%) of 39 patients with bacteremia caused by Enterobacteriaceae were carriers of P. aeruginosa. Bacterial translocation of Enterobacteriaceae was not associated with an abnormally high fecal population of the translocating strain. Prospective quantitative and qualitative analyses of fecal flora were useful in forecasting the most probable translocating gram-negative organism in neutropenic leukemic patients with clinical signs of bacteremia.

Agranulocytosis↗

Pneumococcal bacteremia in Charleston County, South Carolina.

To describe the epidemiology of pneumococcal bacteremia in a large population, this study reviewed medical records for residents of Charleston County, South Carolina, who had pneumococci isolated from blood cultures during the period 1974-1976. The overall incidence of documented pneumococcal bacteremia was 8.5 cases per 100,000 population per year. It was highest for those in the first two years of life (35 per 100,000 per year) and those in their sixties (21 per 100,000 per year). The incidence was more than five times higher in blacks than in whites and within races appeared to be independent of socioeconomic status or population density. Seventy-three per cent of the cases occurred in persons with another medical problem. These data on the incidence of documented pneumococcal bacteremia underestimate the true incidence of bacteremia to the extent that blood cultures were not performed under optimal circumstances for all persons with compatible clinical syndromes. The data suggest that certain groups would benefit from vaccination against pneumococcal disease if the vaccines are shown to be safe and effective for these groups.

Adolescent↗

Bacteremia during diarrhea: incidence, etiology, risk factors, and outcome.

To determine the importance of bacteremia in hospitalized patients with diarrhea in Bangladesh, from September 1982 through August 1983 the authors obtained blood for culture from 1,824 patients who were suspected of having sepsis (44% of all admissions). Nontyphoid bacteremia occurred in 243 patients. The most common pathogens were the Enterobacteriaceae (n = 66 episodes), Staphylococcus aureus (n = 65), Pseudomonas aeruginosa and other non-glucose-fermenting bacilli (n = 50), Streptococcus pneumoniae (n = 40), and Haemophilus influenzae (n = 16). When compared with an equal number of control patients without bacteremia, bacteremic patients were significantly (p less than 0.05) more likely to be under 1 year of age (46.5% of bacteremic patients vs. 30.0% of control patients) and more often had abdominal tenderness (20.1% vs. 11.5%), hypoproteinemia (a serum protein level less than 60 g/liter) (58.9% vs. 42.9%), and a prior intravenous infusion (49.0% vs. 30.9%). The case-fatality rate was 29.7% in bacteremic patients versus 7.8% in controls (relative risk (RR) = 3.8, p less than 0.001). Factors that were associated with an increased risk of death in bacteremic patients were infection with a Gram-negative pathogen (RR = 2.48), decreased peristalsis (RR = 2.66), hypoproteinemia (RR = 3.36), hypothermia (RR = 2.54), and hypotension (RR = 2.19). Bacteremia appears to be an important link between diarrheal illness and death in Bangladesh. In children with diarrhea who are suspected of being septic, early implementation of antimicrobial therapy that is effective against the broad range of pathogens identified appears to be indicated.

Bangladesh↗

Bacteremia following prosthetic valve replacement.

The outcome of patients developing early bacteremia was investigated in 890 patients following cardiac valve replacement over a ten-year period. Thirty-two patients developed bacteremia during the hospital recovery period from valve replacement (3.6%). Sixty per cent of the organisms involved were gram-negative. Twenty-one of 23 patients had white blood counts greater than 14,000 at the time of positive blood culture. Nine patients died, seven of septic complications. Only two patients developed endocarditis. No patient with bacteremia diagnosed within ten days of surgery developed endocarditis, however two patients developed gram-negative sepsis in this period. The diagnosis and treatment of bacteremia requires continual vigilance if significant mortality and morbidity are to be averted.

Aged↗

The triad of Streptococcus bovis bacteremia, colonic pathology, and liver disease.

The association of Streptococcus bovis endocarditis and colon carcinoma has been reported previously in small series in the medical, but not surgical, literature. Although the fecal carriage rate of S. bovis increases with colonic pathology, no explanation exists for the development of bacteremia in these cases. To explore the possible contribution of hepatic dysfunction to the development of portal and systemic bacteremia, the incidence of both colonic pathology and liver disease or dysfunction was determined in 92 patients with S. bovis endocarditis and/or bacteremia. Colonic and liver evaluation had been undertaken in 47% and 93% of patients, respectively. Among these patients, colonic pathology was identified in 51%, and liver disease or dysfunction was documented in 56%. Either the underlying colonic disease or alterations in hepatic secretion of bile salts or immunoglobulins may promote the overgrowth of S. bovis and its translocation from the intestinal lumen into the portal venous system. A compromised hepatic reticuloendothelial system may then contribute to the development of S. bovis septicemia and subsequent endocarditis. We conclude that S. bovis bacteremia is an indication to the clinician of the possibility of underlying liver disease as well as colon pathology.

Colonic Diseases↗

Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control.

OBJECTIVE: To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity, but no trials have examined possible clinical benefits in severely burned patients. DESIGN: Prospective, double-blind, randomized trial. SETTING: Burn intensive care unit of a university hospital. PATIENTS: Twenty-six severe burn patients with total burn surface area of 25% to 90% and presence of full-thickness burns. Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission. Nutritional status and overall inflammation were also measured. INTERVENTION: Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay. MEASUREMENTS AND MAIN RESULTS: The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group (8%) vs. control (43%; p <.04). No difference was seen in the incidence of Gram-positive bacteremia or fungemia. Average number of positive blood cultures, antibiotic usage, and mortality rates also were reduced but did not reach statistical significance. Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury (p <.01 and.04, respectively). C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group (p <.01). CONCLUSIONS: Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients. Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation. In addition, a trend toward lower mortality rate, decreased overall bacteremia incidence, and antibiotic usage in the glutamine group was observed. Glutamine's beneficial effects may be a result of improved gut integrity or immune function, but the precise mechanism of glutamine's protection is unknown.

Adult↗

Bacteremia in ambulatory children.

Bacteremia is a relatively common event in young, apparently mildly ill febrile children. The bacteremia is associated with certain risk factors including age, elevated temperature and high white blood cell count or increased erythrocyte sedimentation rate. The disease and bacteremia clears without antimicrobial agents in some children, but many untreated children have persistent disease. Culture of blood is valuable in children with risk features and may be enhanced in the future as methods for detection of antigen become more widely available. Available data from randomized trials of therapy do not provide clear guidelines for treatment and opinions about optimal management of children at risk for bacteremia vary. My judgement is that presumptive therapy is warranted for the child who is 6 to 24 months of age, who has high fever and has high white blood cell count. Therapy should be effective for the pneumococcus and for H. influenzae. Currently, I recommend amoxicillin or, for children allergic to penicillin, trimethoprim-sulfamethoxazole or cefaclor. After 48 to 72 hours the physician can judge the clinical course and will have data from cultures to base decisions about management of the illness.

Ambulatory Care Facilities↗

Nosocomial bacteremias in measles.

The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions. In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57). Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant. All the isolates from the general patients were fully susceptible to antibiotics. The duration of hospitalization was more than doubled in both groups of affected patients. The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients. Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients.

Adolescent↗

Lack of association between neutropenia and the incidence of bacteremia associated with indwelling central venous catheters in febrile pediatric cancer patients.

To assess the incidence of bacteremia in pediatric cancer patients with indwelling central venous catheters with fever, we reviewed the records of all 67 such patients sequentially admitted during a 10-month period at our institution. There were a total of 140 episodes of fever in these 67 patients. In 55 of the episodes (39%) patients were nonneutropenic (absolute neutrophil count, greater than 500/mm3); 85 episodes (61%) were associated with neutropenia. Twenty-four percent of all episodes of fever in nonneutropenic patients were related to bacteremia vs. 9.5% of episodes of fever in the presence of neutropenia (P less than 0.05). When clinical evidence of an exit site infection was absent, the incidence of bacteremia in the neutropenic and nonneutropenic groups was similar (11% in the neutropenic group; 10% in the nonneutropenic group). We conclude that bacteremia is frequently observed in febrile pediatric cancer patients with indwelling venous catheters who are not neutropenic, particularly if there is clinical evidence of an exit site infection. Thus empiric antibiotic therapy is warranted in all pediatric oncology patients with indwelling catheters who develop fever.

Adolescent↗

Haemophilus influenzae type b unsuspected bacteremia.

To further define the clinical features and natural history of unsuspected Haemophilus influenzae type b (Hib) bacteremia, we retrospectively reviewed the records of 322 Hib infections observed during a 45-month period at Children's Hospital, Boston. We identified 31 patients with unsuspected Hib bacteremia and 19 with unsuspected Hib antigenemia and sterile blood cultures. Bacteremic patients were typically under two years of age (81%), had high fevers (mean = 39.5 degrees C), and frequently had otitis media (65%) diagnosed as their only focus of infection at presentation. Nineteen of 31 were empirically treated with oral antibiotics. Ten of 31 (32%) developed focal infectious complications consisting of meningitis (n = 7), cellulitis (n = 2), and pneumonia (n = 1). Children with focal infectious complications differed from those without infectious complications in having a significantly higher mean fever of 40.3 degrees C compared to 39.7 degrees C (P less than 0.05). Five of 19 (26%) empirically treated patients developed focal complications (all meningitis) compared to five of 12 (42%) untreated patients. Blood cultures at follow-up visit were positive in three of 19 (9%) treated patients and seven of 12 (42%) untreated patients (P less than 0.05). Of the 19 children with antigenemia and sterile blood cultures, 16 (84%) were empirically treated with antibiotics, and none had positive blood cultures or focal infections on follow-up evaluation. Children with occult Hib bacteremia are at high risk for developing serious focal infections, particularly meningitis, despite empiric antibiotic therapy. Once Hib bacteremia is suspected, strong consideration should be given to parenteral in hospital antibiotic therapy. The utility of rapid antigen detection for identifying high-risk patients requires further evaluation.

Antigens, Bacterial↗

Risk of bacteremia after endotracheal intubation for general anesthesia.

Blood cultures were obtained before and after endotracheal intubation to assess the risk of bacteremia associated with this procedure and to evaluate the need for prophylactic antibiotics to prevent bacterial endocarditis in patients with structural heart disease requiring general anesthesia. Blood cultures were obtained immediately before intubation and two and ten minutes after intubation in 50 individuals without evidence of structural heart disease who required general anesthesia for elective surgery. Of 32 who had orotracheal intubation, only one demonstrated postintubation bacteremia; of 18 individuals who had nasotracheal intubation, none had evidence of bacteremia. These data suggest that in healthy individuals undergoing endotracheal intubation under direct vision the risk of bacteremia is quite small (about 2%).

Adolescent↗

Retrospective study of outcome in patients treated for Staphylococcus aureus bacteremia.

OBJECTIVE: To investigate whether a change in current treatment practice for Staphylococcus aureus bacteremia from flucloxacillin and aminoglycoside to flucloxacillin and fusidic acid was associated with any changes in outcome. METHODS: A retrospective analysis was carried out of 316 episodes of S. aureus bacteremia diagnosed and treated in a tertiary hospital complex between 1983 and 1993. Outcomes considered were (1) death related to the infection and (2) relapse following cessation of antibiotic therapy. RESULTS: Mortality related to infection, which occurred in 24% of patients, was unrelated to treatment with the combination of flucloxacillin and fusidic acid; however, increasing age was a significant risk factor (OR per decade=1.35, 95% CI=1.18-1.55), and increasing duration of treatment (OR per week of treatment=0.63, 95% CI=0.52-0.77), use of flucloxacillin (OR=0.30, 95% CI=0.14-0.64), presence of an intravascular device (OR=0.39, 95% CI=0.20-0.78) and presence of a skin lesion (OR=0.51, 95% CI=0.26-0.99) were significant protective factors. The only factor significantly related to relapse, which occurred in 11% of patients, was treatment with the combination of flucloxacillin and fusidic acid (OR=0.32, 95% CI=0.12-0.85). There was approximately a 70% reduction in the risk of relapse if this combination was used. CONCLUSIONS: This retrospective analysis suggests a clinically important protective effect of fusidic acid against relapse in patients with S. aureus bacteremia. Although the results were adjusted for potential confounding factors, the possibility of bias remains. There is a need for a prospective randomized trial to evaluate the effectiveness of flucloxacillin and fusidic acid for treating S. aureus bacteremia.

Journal Article↗

Evaluation of tumor necrosis factor-alpha, interleukin-6 and C-reactive protein plasma levels as predictors of bacteremia in patients presenting signs of sepsis without shock.

OBJECTIVE: To evaluate the sensitivity of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) plasma measurement to detect bacteremia in patients presenting sepsis signs, and to evaluate the potential benefit of such measurement in terms of early antimicrobial therapy initiation. METHODS: Plasma was obtained from 166 hospitalized patients for whom blood cultures were drawn for sepsis. Clinical data and antimicrobial therapies were noted. IL-6, TNF and C-reactive protein (CRP) were measured. The sensitivities of these markers were retrospectively compared with the accuracy of the attending physician in initiating empirical antimicrobial therapy. The setting was an 850-bed university hospital. RESULTS: Thirty-four bacteremias and 69 non-bacteremic infections were noted. In 63 others, no infection was documented. Median (range) IL-6 plasma levels in the three groups of patients were 462 (15--50 850), 189 (<15--38 300) and 91 (<10--13 750) pg/mL, respectively (p<0.01). The corresponding TNF-alpha plasma levels were 37.5 (<15--2400), 15 (<15--240) and 15 (<15--200) pg/mL, respectively (p<0.01). CRP plasma levels were 10.7 (<0.6--30.2), 10.3 (<0.6--34.4) and 7.3 (<0.6--20.9) mg/dL, respectively (p=0.12). With respect to these three parameters, IL-6 and TNF-alpha appear better than CRP for predicting bacteremia. Clinical features resulted in starting empirical antimicrobial therapy in only 62% of the bacteremic patients. On the other hand, 68% of these bacteremic patients had high IL-6 plasma levels (>200 pg/mL). A combination of clinical features and high IL-6 levels would have permitted early treatment for 82% of the bacteremic patients. CONCLUSIONS: IL-6 and TNF-alpha thus appear to be useful and earlier markers of bacteremia in septic patients. By contrast, CRP is neither sensitive nor specific in this setting.

Journal Article↗

Use of molecular typing to investigate bacterial translocation from the intestinal tract in malnourished children with Gram-negative bacteremia.

OBJECTIVE: To investigate whether translocation of intestinal Enterobacteriaceae was a likely source of bacteremia in children of 2 years or less hospitalized for fever and moderate malnutrition. METHODS: Blood and fecal cultures were obtained from 198 such children admitted in the Princess Basma Hospital (Irbid, Jordan). Enterobacteriaceae isolated from blood cultures were compared with those present in fecal cultures by genomic typing using pulsed-field gel electrophoresis. The characteristics of children whose blood and fecal strain typing patterns were not distinguishable, i.e. with documented translocation, were compared to those of children without documented translocation. RESULTS: Bacterial translocation was documented in 12 of 19 children (63%) with Enterobacteriaceae bacteremia for whom paired blood and fecal strains were available for genomic typing, and was thus the major source of these bacteremias. The clinical or biological signs of malnutrition were not significantly more pronounced in the bacteremic children with documented translocation than in those without. CONCLUSIONS: We demonstrated that bacterial translocation from the intestinal tract was the most common source of Gram-negative bacteremia in the population studied.

Journal Article↗

Protection against group B meningococcal disease: evaluation of serotype 2 protein vaccines in a mouse bacteremia model.

A mouse bacteremia model was used to evaluate the immunogenicity and protection against challenge provided by five different meningococcal serotype 2 vaccines. Mice vaccinated with serotype 2 protein vaccines had levels of bacteremia reduced by at least 100-fold after challenge with group B serotype 2 miningococci. Mice vaccinated with serotype 2 protein vaccine and challenged with group C serotype 2 meningococci showed 10-fold or less reduction in bacteremia. Vaccines were primarily serotype specific since no increase in protection was observed after challenge with either group B serotype 4 or group C nontypable meningococci. Serotype 2 antibody levels, measured by the bactericidal assay and the enzyme-linked immunosorbent assay 3 weeks after immunization, demonstrated a graded dose-response which correlated with protection up to 40 weeks after vaccination with a single 10- or 25-micrograms dose of serotype 2 protein vaccine. A 1-microgram booster dose of serotype 2 vaccine, given 2 weeks after primary immunization, significantly increased both bactericidal (P less than 0.01) and enzyme-linked immunosorbent assay (P less than 0.02) titers. The data obtained from the mouse bacteremia model indicate that serotype 2 protein vaccines are stable and immunogenic, and protect mice against challenge with group B serotype 2 meningococci.

Animals↗

Production of bacteremia and meningitis in infant rats with group B streptococcal serotypes.

Group B streptococcal strains, representing the five major serotypes, were inoculated into infant rats by intranasal, oral, and intraperitoneal routes. Bacteremia regularly followed injection by the intraperitoneal route. Four strains (three of type III) isolated from human cerebrospinal fluid appeared more virulent for 5-day-old rats. Injection of fewer than 10 colony-forming units of one strain, a type III, led to bacteremia and death in 27% of animals. The cumulative bacteremia and mortality rate with this strain was 66% in animals given inocula of less than 10 to 10(3) colony-forming units. Bacteremia developed by 24 to 48 h with concentrations of greater than 10(5) colony-forming units per ml of blood, and death occurred soon afterward. Among bacteremic animals, positive cerebrospinal fluid cultures were found in 97%, and cerebrospinal fluid bacterial concentrations were equal to or exceeded bacterial counts in blood. The susceptibility of infant rats to infection with type Ia, Ic, or III strains was age dependent. Histopathological studies of the brain and meninges in 34 bacteremic animals with culture-positive cerebrospinal fluid revealed that 5- to 10-day-old animals had numerous bacteria distributed in a perivascular pattern but, with one exception, no leukocytic infiltration. In contrast, three of the 11- to 12-day-old and two 15-day-old animals had very thickened meninges infiltrated with polymorphonuclear leukocytes, macrophages, and bacteria.

Animals↗

Enhancement of experimental bacteremia and endocarditis caused by dysgonic fermenter (DF-2) bacterium after treatment with methylprednisolone and after splenectomy.

The dysgonic fermenter-2 bacterium is a newly recognized fastidious gram-negative bacillus that causes bacteremia and sometimes endocarditis in immunocompromised persons after they are bitten by dogs. To develop an experimental model of this infection, we placed polyethylene catheters across the aortic valves of New Zealand white rabbits, which were inoculated intravenously the next day with dysgonic fermenter-2 bacteria. After 1 week, the rabbits were killed and the endocardial vegetations were homogenized for quantitative culture. Large inocula (1.3 X 10(10) to 2.1 X 10(10) viable bacteria) were required to produce infected vegetations. All infected rabbits had negative blood cultures at the time of autopsy and most developed serum agglutinins against dysgonic fermenter-2 bacteria. Three daily injections of methylprednisolone (30 mg/kg), starting the day before inoculation, significantly increased the incidence of endocarditis and the number of bacteria per gram of infected vegetation (P less than 0.05). Treatment with methylprednisolone prolonged the initial bacteremia and caused significant increases in the numbers of bacteria per gram of blood, spleen, and liver compared with those of untreated controls (P less than 0.05). Rabbits that had previously undergone splenectomy showed prolongation of the initial bacteremia but no significant increase in the incidence of infected vegetations. These results showed that the dysgonic fermenter-2 bacterium is a pathogen that causes endocarditis in rabbits but that it requires a large inoculum and produces blood culture-negative infections. Treatment with methylprednisolone enhances infection by prolonging the initial bacteremia and probably by diminishing bactericidal activity in the vegetations.

Animals↗

Haemophilus influenzae type b infection in childhood: history of bacteremia and antigenemia.

Groups of children (mean age, 31.4 months) with Haemophilus influenzae type b meningitis, epiglottitis, or septic arthritis were tested for the presence and levels of bacteremia, capsular polyribophosphate (PRP) antigenemia, and development of specific antibody in serum after the onset of acute illness. Although bacteremia cleared promptly after antibiotic therapy, circulating PRP could be detected in serum for relatively long periods, with 51% of the patients still having detectable antigen after 30 days postinfection. Even in the presence of specific antibody, antigenemia persisted for as long as 47 days after admission. It was observed that there was no statistically significant correlation between the persistence of antigenemia and age (P greater than 0.2), the initial antigen concentration (P greater than 0.50), or the development of antibody (P greater than 0.20). The presence of a low magnitude of bacteremia (less than 300 organisms per ml) was associated with a maximum concentration of 10 ng of PRP per ml. On the other hand, bacterial counts in excess of 10(4)/ml were associated with greater than 1,000 ng of PRP per ml (r = 0.98, r2 = 0.96, P less than 0.001). It was observed that the amount of circulating PRP in the acute phase of illness was related to whether a child developed convalescent-phase antibody. Invariably, the younger children, who primarily had meningitis, had a PRP concentration of greater than 10 ng/ml and failed to develop an antibody response in any isotype, whereas the older patients, who primarily had infections other than meningitis, had a PRP concentration of less than 10 ng/ml and a 45.5% success rate in developing an antibody response (P = 0.006). These findings suggest that there is a direct correlation between the magnitudes of bacteremia and antigenemia, that antigen may persist for long periods even in the presence of antibody, and that the level of antigenemia in addition to the patient age is significantly related to the nature of the convalescent-phase antibody response.

Age Factors↗