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Antibody responses to Escherichia coli J5 lipopolysaccharide and to Salmonella porin in patients with bacteremia.

This study was undertaken in order to evaluate whether patients with bacteremia respond with antibodies directed towards two outer membrane components of Gram-negative bacteria. The antibody responses to the core of the lipopolysaccharide molecule (LPS) of the rough E. coli J5 mutant and to a purified outer membrane protein (porin) from Salmonella were studied in bacteremic patients. Two or three serum samples were consecutively collected from 77 patients having 82 episodes of bacteremia altogether, of these 50 were caused by bacteria of the genus Enterobacteriaceae. As controls, sera from 82 age and sex matched patients and 100 healthy blood donors were analysed. The antibody titers were assessed by enzyme-linked immunosorbent assays (ELISA). None of the patients with bacteremia responded with an increase in antibody level to the E. coli J5 rough LPS. This finding indicates that the core portion of the E. coli J5 LPS contains no antigenic epitopes immunologically cross-reactive with Gram-negative bacteria causing bacteremia. By contrast, 13 patients showed significant titer increases to the porin preparation derived from Salmonella. Twelve of these patients had bacteremia caused by Gram-negative organisms belonging to Enterobacteriaceae. One patient had bacteremia with Bacteroides fragilis but also suffered from a severe peritonitis with growth of both E. coli and Klebsiella. It is suggested that the measurement of antibody response to porin may be of value for differential serological diagnosis in patients with bacteremia, to distinguish between Enterobacteriaceae and other organisms.

Adult↗

Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group.

BACKGROUND: HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. METHODS: To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected. CONCLUSIONS: HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Antibodies, Monoclonal↗

Influence of matching for exposure time on estimates of attributable mortality caused by nosocomial bacteremia in critically ill patients.

OBJECTIVE: To evaluate the influence of matching on exposure time on estimates of attributable mortality of nosocomial bacteremia as assessed by matched cohort studies. DESIGN: Two retrospective, pairwise-matched (1:2) cohort studies. SETTING: A 54-bed intensive care unit (ICU) in a university hospital. PATIENTS: Patients with nosocomial Escherichia coli bacteremia (n = 68) and control-patients without nosocomial bacteremia (n = 136 for each matched cohort study). INTERVENTION: In both matched cohort studies, the same set of bacteremic patients was matched with control-patients using the APACHE II system. In the first study, control-patients were required to have an ICU stay at least as long as the respective bacteremic patient prior to onset of bacteremia (matching on exposure time). In the second study, control-patients were required to have an ICU stay shorter than the stay prior to the development of bacteremia in the respective bacteremic patient (no matching on exposure time). RESULTS: For bacteremic patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6 days). In the first matched cohort study, hospital mortality was not different between bacteremic patients and control-patients (44.1% vs 43.4%; P = .999). In the second study, mortality of bacteremic patients and control-patients was also not different (44.1% vs 47.8%; P = .657). Mortality rates between control groups were not different (43.4% vs 47.8%; P = .543). CONCLUSION: Matching or not matching on exposure time did not alter the estimate of attributable mortality for ICU patients with E. coli bacteremia.

APACHE↗

Prediction by surveillance cultures of bacteremia among neutropenic patients treated in a protective environment.

One hundred seventy-five consecutive marrow transplant patients who were treated in a protective environment for at least two weeks were studied to determine the usefulness of bacteriologic surveillance cultures for the prediction of bacteremia due to Staphylococcus aureus or aerobic gram-negative bacilli. Bacteremia with these organisms occurred in 15 patients (9%), and all patients were colonized with the respective organism before bacteremia occurred. Bacterial colonization was associated with a 17- to 174-fold increase in the relative risk of bacteremia. Negative predictive values were high, but positive predictive values were low owing to the infrequent occurrence of bacteremia. Surveillance cultures also predicted antibiotic sensitivities for all but one organism causing bacteremia. Bacteriologic surveillance cultures in the protective environment are thus useful both for the identification of patients at higher risk of bacteremia with certain types of organisms and for the identification of those who may fail to respond to antibiotic therapy as a result of infection with resistant organisms.

Adolescent↗

Role of intravascular replication in the pathogenesis of experimental bacteremia due to Haemophilus influenzae type b.

The potential role of extravascular and intravascular replication was studied in initiation of sustained bacteremia in experimental infection due to Haemophilus influenzae type b. When organs and fluid from rats were cultured after intranasal inoculation of the rats with H. influenzae type b, the organism was not recovered from any putative extravascular focus before development of bacteremia. To evaluate the potential contribution of intravascular replication in initiation of bacteremia due to H. influenzae type b, we obtained serial blood cultures after intravenous or intranasal inoculation. Bacterial counts increased exponentially immediately after intravenous and 12-18 hr after intranasal inoculation. Using the same model system, we observed bacteremia due to Streptococcus pneumoniae after intraperitoneal but not intravenous inoculation. After intraperitoneal inoculation, the magnitude of bacteremia in individual rats did not regularly increase exponentially over time. These findings are consistent with extravascular replication leading to bacteremia due to S. pneumoniae and efficient intravascular replication leading to sustained bacteremia due to H. influenzae type b.

Animals↗

The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents.

Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.

Acquired Immunodeficiency Syndrome↗

Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding.

Coagulase-negative staphylococci are the most common cause of bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and the Children's Hospital, Boston, Massachusetts. In 1982, nosocomial bacteremia with coagulase-negative staphylococci occurred in 45 of 882 (5.1%) infants admitted to these units who survived and remained in intensive care for more than 48 hours and were therefore at risk. The overall cumulative incidence (attack rate) of nosocomial bacteremia rose dramatically with decreasing birth weight. The smallest infants, those with birth weights of less than 750 g, experienced an overall risk of nosocomial bacteremia 44.5 times that of infants with birth weights of greater than 2,000 g. A large part of the excess risk for small babies was attributable to their longer hospitalizations. However, after adjustment for length of stay, the smallest infants still suffered a daily rate of bacteremia (incidence density) 5.3 times that of the largest, indicating a considerable residual effect of birth weight on the daily risk of nosocomial coagulase-negative staphylococcal bacteremia. The results were similar in the two nurseries. Thus, there is still a substantially increased intrinsic risk of nosocomial coagulase-negative staphylococcal bacteremia among infants with very low birth weights, even after adjustment for duration of hospitalization, and differences in birth weight can confound comparative studies.

Birth Weight↗

Factor XIII as a modulator of plasma fibronectin alterations during experimental bacteremia.

Fibronectin is found in plasma as well as in association with connective tissue and cell surfaces. Depletion of plasma fibronectin is often observed in septic trauma and burned patients, while experimental rats often manifest hyperfibronectinemia with sepsis. Since Factor XIII may influence the rate of clearance and deposition of plasma fibronectin into tissues, we evaluated the temporal changes in plasma fibronectin and plasma Factor XIII following bacteremia and RE blockade in rats in an attempt to understand the mechanism leading to elevation of fibronectin levels in bacteremic rats, which is distinct from that observed with RE blockade. Clearance of exogenously administered fibronectin after bacteremia was also determined. Rats received either saline, Pseudomonas aeruginosa (1 X 10(9) organisms), gelatinized RE test lipid emulsion (50 mg/100 gm B.W.), or emulsion followed by Pseudomonas. Plasma fibronectin and Factor XIII were determined at 0, 2, 24, and 48 hours post-blockade or bacteremia. At 24 and 48 hr following bacteremia alone or bacteremia after RE blockade, there was a significant elevation (p less than 0.05) of plasma fibronectin and a concomitant decrease (p less than 0.05) of plasma factor XIII activity. Extractable tissue fibronectin from liver and spleen was also increased at 24 and 48 hours following R.E. blockade plus bacteremia. In addition, the plasma clearance of human fibronectin was significantly prolonged (p less than 0.05) following bacterial challenge. Infusion of activated Factor XIII (20 units/rat) during a period of hyperfibronectinemia (908.0 +/- 55.1 micrograms/ml) resulted in a significant (p less than 0.05) decrease in plasma fibronectin (548.5 +/- 49.9 micrograms/ml) within 30 min. Thus Factor XIII deficiency in rats with bacteremia may contribute to the elevation in plasma fibronectin by altering kinetics associated with the clearance of fibronectin from the blood.

Animals↗

Epidemiology of Staphylococcus aureus bacteremia in Denmark from 1957 to 1990.

OBJECTIVE: To investigate the changes in epidemiology of Staphylococcus aureus (SA) bacteremia in Denmark over a 30-year period, where the population has remained stable. METHODS: Bacteriologic and clinical data were generated on 17 712 SA strains from virtually all SA bacteremia cases in Denmark from 1957 to 1990 submitted to our laboratory for phage typing. The data were related to information about population, hospital activity and blood-culturing activity during that period. RESULTS: SA bacteremia cases increased from 3 to 20/100 000 inhabitants per year, with the largest increases in incidence rates for the <1-year and >50-year age groups. While blood-culturing activity increased three-fold during the period, the rate of SA bacteremias actually decreased relative to the number of blood cultures taken. The increase in SA bacteremia cases was mainly due to increases in nosocomial infections for all age groups and was related to the increasing admission rates to Danish hospitals. Major shifts in antibiotic resistance patterns and phage types took place during the period, i.e. a marked reduction in multiresistant (including methicillin-resistant) strains, but could not explain the change in the epidemiology of the infections. CONCLUSIONS: The data indicate that increases in SA bacteremia rates correlated significantly with increasing numbers of admissions to hospitals. The main increase in SA bacteremia rates was represented by nosocomial infection, although increasing blood-culturing activity during the period may have contributed.

Journal Article↗

Gram-negative bacillary bacteremia in the elderly: incidence, ecology, etiology, and mortality.

The incidence, ecology, and mortality of gram-negative bacillary bacteremia in elderly patients were studied in an analysis of 334 episodes over a four-year-period in a 489-bed North Carolina community teaching hospital, 135 (40.4%) of which occurred in patients 70 years of age or older. The bacteremia rate per 1000 hospital admissions increased sharply with increasing age. The ecology and in vitro antimicrobial susceptibilities of the bacterial isolates were strongly influenced by community v hospital acquisition, but not by age. Urosepsis was significantly more likely to be the underlying source of hospital-acquired bacteremia in patients 70 years or older (P less than 0.01). Total bacteremia-related mortality did not increase with increasing age; in the group of patients aged 70 years or older with nonfatal/ultimately fatal underlying diseases (NF/UFUD), however, mortality was 9.1% compared to 2.9% in the younger age group (P less than 0.001). Significantly increased bacteremia-related mortality was also noted in the older patients with NF/UFUD admitted from nursing homes (P less than 0.05) and those not treated with an appropriate antimicrobial agent within 24 hours (P less than 0.01). Overall, the older patients with hospital-acquired bacteremia, neutropenia-associated infection, those bacteremic from a nonurinary source of infection, and those treated with multiple-drug regimens had higher mortality (P less than 0.05). Gram-negative bacteremia is much more common in patients 70 years of age or older and compared with younger patients mortality appears to be significantly increased for the important subgroup of older patients with nonfatal or ultimately fatal underlying diseases.

Adolescent↗

Clinical correlates of bacteremia in a Veterans Administration extended care facility.

Little is known about bacteremia in long-term care facilities. We have conducted a retrospective study during a 12-month period analyzing the clinical correlates of bacteremia in 533 chronically institutionalized, predominantly male patients, with an average age of 69 years. Thirty-four men had forty-two bacteremic illnesses during this period. The incidence rate was 0.30 episodes per 1000 patient care days, and the mortality rate was 21%. The urinary tract was the most frequently identified tissue source (56%), followed by respiratory tract (7%) and skin (7%). Providencia stuartii was the most common gram-negative organism, while Staphylococcus aureus, Streptococcus pneumoniae and enterococcus were the frequent gram-positive microbes. Gram-negative bacteremia accounted for 63% of the episodes (15% mortality rate), and gram-positive bacteremia accounted for 27% (18% mortality rate); 10% of the bacteremias were polymicrobial (25% mortality rate). Most of the isolated organisms were sensitive to available antimicrobial agents. The leading risk factor for bacteremia was an indwelling urinary catheter (odds ratio 39, 95% confidence limits 16 to 97). Patients with urinary catheters at the beginning of the study constituted only 5% of the population, but accounted for 40% of the gram-negative bacteremias during the year of observation.

Aged↗

[Pseudomonas aeruginosa bacteremia associated with hematologic disorders [I]. Predisposing factors and clinical manifestations].

We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders in a 16-year period. Ninety-five percent of the patients had hematologic malignancies such as acute leukemia. All but one patient received cytotoxic or immunosuppressive therapy at or prior to the onset of bacteremia. Seventy-seven percent of the episodes occurred during profound granulocytopenia of below 100/mm3. All the patients acquired their infection in the hospital, and 96% had received antibiotic therapy during the preceding two weeks. Periodontal, anorectal, lower respiratory tract, and urogenital infections were the sources of bacteremia in about three-quarters of the episodes. Periodontal infection tended to progress to cellulitis of the face or the floor of the mouth, often resulting in bacteremia of the unimicrobial type, while anorectal infection predisposed to abscess formation, frequently leading to bacteremia of the polymicrobial type. Cellulitis at onset was seen in 35% of the episodes. Most sites of infection did not become apparent until one to three days after the onset of fever, probably because of depressed inflammatory response associated with severe granulocytopenia. The majority of patients complained of gastrointestinal symptoms such as nausea and vomiting, abdominal pain, diarrhea, and abdominal fullness at the onset of bacteremia. Major complications included bacteremic shock (63%), impaired consciousness (25%), ecthyma gangrenosum or hemorrhagic gangrenous cellulitis (18%), and jaundice (12%). Furthermore, there were one case each of endocarditis and disseminated intravascular coagulation. It was thus suggested that the clinical picture of P. aeruginosa bacteremia complicating hematologic disorders is influenced by the predisposing conditions associated with the underlying diseases and their treatment.

Acute Disease↗

[Investigation on the etiology of sepsis by using experimental mouse model with leukocytopenia. 3. The role of Kupffer cells in the etiology of bacteremia].

In the previous report, we showed that the reticuloendothelial system (RES), especially the liver, played an important role in the etiology of bacteremia or sepsis as the major protective system. In this study, to investigate the role of Kupffer cells in the etiology of bacteremia, we isolated and cultured murine Kupffer cells using a technique involving perfusion with collagenase and DNase. We compared the adherence and phagocytosis rate of two groups of isolated bacteria from bacteremic mice by these cells. One group was bacteria causing systemic bacteremia consisted of P. aeruginosa and M. morganii, and the other was bacteria causing portal bacteremia consisted of E. coli, E. cloacae, K. pneumoniae and Enterococci. As a consequence, the following facts were revealed. 1. The bacterial phagocytosis and adherence rate by Kupffer cells were significantly higher in bacteria causing portal bacteremia than in bacteria causing systemic bacteremia. These data were correlated to each blood clearance rate from mice. 2. Blood clearance rate reflected mainly adherence of Kupffer cells to bacteria, and it was suggested that these adherence were one of the most important factor to protect the hosts from the advance of bacteremia from the portal to the systemic. 3. In the case of using peritoneal macrophage, we couldn't find the same correlation, so the possibility was suggested that the above phenomenon was specific to Kupffer cells.

Animals↗

Role of nasopharyngeal colonization with and without bacteremia in the protection of infant rats against Haemophilus influenzae type b challenge.

Nasopharyngeal colonization of infant rats with Haemophilus influenzae type b was investigated by two methods of intranasal inoculation. After traumatic instillation of the bacteria, 100% of the animals became colonized, compared with 75.5% of animals after atraumatic instillation. Among colonized rats, significantly more animals in the traumatic group developed bacteremia compared with those in the atraumatic group. Rats in the traumatic group had an onset of bacteremia at a mean of 2.6 days after inoculation compared with 7.3 days in the atraumatic group. The duration of colonization and bacteremia was the same in both groups. The majority of heavily colonized rats developed bacteremia compared with none of the lightly colonized rats. Thus, the development of bacteremia appeared to be related independently to both heavy colonization and traumatic instillation. Protection against intraperitoneal bacterial challenge with H. influenzae type b developed in rats that had been bacteremic; in the majority of animals, this correlated with the development of serum bactericidal activity. Protection and bactericidal activity were only rarely observed in nonbacteremic rats that had been either heavily or lightly colonized. The development of serum bactericidal activity was not related to either the duration or peak level of bacteremia. Thus, in this rat model, H. influenzae type b nasopharyngeal colonization without bacteremia did not appear to stimulate circulating antibodies that protected the animals against challenge.

Animals↗

Comparison of community-acquired and nosocomial pneumococcal bacteremia.

We evaluated pneumococcal bacteremia retrospectively for 3.5 yr. Sixty-three episodes occurred in 62 patients; 37 were nosocomial in origin; 26 were community-acquired. Pneumococcal bacteremia was most common between January and June. Patients with nosocomial disease had significantly more ultimately fatal disease and sustained more manipulation of the respiratory tract than patients with community-acquired bacteremia. The mortality of nosocomial pneumococcal bacteremia (75.8%) or nosocomial pneumococcal pneumonia with bacteremia (66.7%) was significantly greater than community-acquired bacteremia (26.9%; p less than 0.01) or pneumonia with bacteremia (18.2%; p less than 0.001). All 62 patients were eligible for pneumococcal vaccine, and 57 could have received immunoprophylaxis. A vaccine trial is indicated in the hospital setting.

Cross Infection↗

Bacteremia in children following dental extraction.

The incidence and intensity of bacteremia following tooth extraction in children were measured by blood culture. The effects on bacteremia of the number and type of teeth extracted, oral hygiene, gingival health, presence of abscess, and antibiotic prophylaxis were assessed. Antibiotic prophylaxis reduced the incidence of bacteremia from 63% to 35%. The intensity of bacteremia was 2 cfu/mL of blood or less in 80% of the children. An agar pour-plate method of blood culture was significantly more effective than broth in culturing the small volumes of inoculum. Of 83 bacterial strains characterized, 39 were strict anaerobes or micro-aerophilic, and the remainder mainly streptococci. S. mitior and S. sanguis were most commonly isolated, often in pure culture, and were generally sensitive to antibiotics. No direct association was demonstrated between the plaque and gingival indices and incidence of bacteremia or between the number of teeth extracted and the incidence or intensity of bacteremia. It is concluded that all children at risk from infective endocarditis require antibiotic prophylaxis prior to tooth extraction, since it is impossible for the likelihood or intensity of transient bacteremia to be clinically predicted.

Adolescent↗

Bacteremia in adult diabetic patients.

OBJECTIVE: To compare the microbiology, sources, complications, and outcome of bacteremia in diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS: A prospective study was conducted of all episodes of bacteremia in hospitalized diabetic and nondiabetic patients. The study consisted of patients greater than or equal to 18 yr of age with bacteremia detected within a 19-mo interval. RESULTS: We compared 124 episodes of bacteremia in 119 diabetic patients to 508 episodes in 480 nondiabetic patients. Diabetic patients were older than nondiabetic patients (median age 74 vs. 68 yr, P = 0.0001). In patients with an indwelling urinary catheter and bacteremic urinary tract infection, the percentage of Klebsiella in diabetic patients was 60% (6 of 10) and in nondiabetic patients was 17% (4 of 23, P = 0.04). In patients without an obvious source of bacteremia, the percentage of staphylococcal isolates in diabetic patients was 29% (10 of 35) and in nondiabetic patients was 14% (24 of 176, P = 0.04). Staphylococci were a common cause of bacteremic infections of the extremities in diabetic patients (12 of 19, 63%) and nondiabetic patients (20 of 50, 40%). Septic shock was the only complication that was more common in diabetic patients. The mortality in diabetic and nondiabetic patients was 28 and 29%, respectively. CONCLUSIONS: Our results represent elderly patients with non-insulin-dependent diabetes mellitus. In this group, empirical treatment for suspected bacteremic urinary tract infection in patients with a urinary catheter should include coverage for Klebsiella. Empiric treatment for suspected bacteremia of unknown origin or caused by infection of the extremities should include an antistaphylococcal drug. The prognosis of bacteremia in diabetic and nondiabetic patients was similar.

Adult↗

The spectrum of Bacillus bacteremias in heroin addicts.

Bacillus bacteremias occurred in two heroin addicts. The first patient had one day of fever and chills after intravenous heroin use. Persistent cereus bacteremia consistent with endocarditis was documented and responded to four weeks of antibiotic therapy. The second patient had non-cereus Bacillus species isolated from blood cultures three times over eight days, each time after renewed heroin use. The patient remained well, and the bacteremias cleared spontaneously. Because Bacillus species frequently contaminate heroin injection materials and because the Bacillus bacteremias were temporally associated with intravenous heroin use, Bacillus bacteremias in both patients probably eventuated from heroin abuse. These cases, in conjunction with two previously reported cases of Bacillus endocarditis in heroin addicts, suggest that heroin addicts are at risk for developing Bacillus bacteremias, which may vary in severity from endocarditis to benign transient bacteremias.

Bacillus↗