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Transient bacteremia and endocarditis prophylaxis. A review.

Transient, usually asymptomatic bacteremia occurs in a wide variety of procedures and manipulations, particularly those associated with mucous membrane trauma. It may also occur with such daily functions as tooth brushing and bowel movements. These brief bacteremias are especially common in tooth extraction and other dental procedures. Although numerical risk is uncertain, these bacteremias can occasionally give rise to infective endocarditis in the susceptible patient. While no proof exists that antibiotics given prior to procedures causing bacteremia prevent endocarditis in humans, experimental evidence in rabbits supports their use. Therefore, in situations where bacteremia is highly predictable, it would seem wise to administer prophylactic antimicrobials. Procedures in the susceptible host where prophylactic antibiotics seem prudent include dental manipulations and urinary tract instrumentation. Whether patients with acquired valvular or congenital heart disease who are to undergo abdominal surgical procedures should routinely receive prophylactic antibiotics is unclear. However, until the incidence of transient bacteremia associated with various abdominal procedures is further defined, endocarditis-prone patients should probably receive prophylaxis. Furthermore, patients with prosthetic valves who are subjected to upper gastrointestinal endoscopy, sigmoidoscopy, liver biopsy, or barium enema should also probably have antibiotic pretreatment. For dental procedures and for upper gastrointestinal endoscopy in patients with prosthetic valves, a combination of penicillin and streptomycin or vancomycin alone is recommended. For urinary tract instrumentation in all patients and for sigmoidoscopy, liver biopsy, or barium enema in patients with prosthetic valves, prophylaxis should be with ampicillin and gentamicin or vancomycin and gentamicin.

Anti-Bacterial Agents

Teichoic acid antibody test: its use in patients with coagulase-positive staphylococcal bacteremia.

We have studied the occurrence and specificity of teichoic acid antibodies (TAAs), measured by double diffusion in agar, in 114 patients with bacteremia of whom 47 had coagulase-positive staphylococcal bacteremia. A total of 30% of the 47 patients with coagulase-positive staphylococcal bacteremia had a TAA titer of 1:8 or more, and an additional 30% had a titer of 1:2 or 1:4. High TAA titers were most often connected with coagulase-positive staphylococcal endocarditis, osteomyelitis, and deep wound infections. None of the six coagulase-negative patients with staphylococcal bacteremia nor any of the 92 controls had titers exceeding 1:1. A total of 10% of the other patients with bacteremia showed positive results on the TAA test at low titer levels. Compared to the antistaphylolysin value, the TAA test was about equally specific but more sensitive.

Adolescent

Simultaneous antibiotic levels in "breakthrough" gram-negative rod bacteremia.

Of 237 cases of gram-negative rod bacteremia observed at the UCLA Medical Center during a 12 month period, 52 (22 per cent) occurred while the patient was receiving antibiotics which inhibited the infecting organism by disc diffusion tests. One half of the plasma samples available from 42 such patients with "breakthrough" bacteremia had subinhibitory circulating antibiotic levels when cultures were positive. Sepsis documented within 72 hours of initiation of therapy was usually due to antibiotic-sensitive Esch. coli and was associated with inadequate antibiotic levels; the patient was usually treated with a penicillin or cephalosporin. The source of bacteremia was most frequently the urinary tract or the biliary tree. In contrast, sepsis occurring more than 72 hours after the administration of antibiotics was frequently caused by multiple antibiotic-resistant Esch. coli in patients treated with gentamicin in adequate dosage and was associated with leukopenia or undrained purulent collections. Therapy ultimately failed in 20 cases (48 per cent): in early "breakthrough" bacteremia, failure was associated with subinhibitory antibiotic levels, and in late "breakthrough" bacteremias with inadequate drainage or impaired host defenses.

Anti-Bacterial Agents

Pseudomonas bacteremia. Review of 108 cases.

The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.

Anti-Bacterial Agents

Detection and quantitation of bacteremia in childhood.

Quantitative blood cultures were sought in 383 children, from whom routine blood cultures were obtained because of fever, by direct plating of 10 and 100 microliter blood onto solidified media. There were 14 positive cultures from 12 patients. These were 7 Hemophilus influenzae type b, 5 Streptococcus penumoniae, and 2 Staphylococcus aureus. The direct-plating technique permitted more rapid identification of positive cultures, and detected three episodes not identified by routine broth culture. Bacterial counts ranged from 20 to greater than 10(4) bacteria/ml blood. In the three cases of H. influenzae type b meningitis, bacteremia exceeded 10(3)/ml. Among nine patients in whom bacteremia was unassociated with meningitis, (bacteremia without evident localized disease 5, pneumonia 2, epiglottitis 1, peritonitis 1), bacteremia was less than 10(3)/ml. This technique may aid detection of bacteremia and help identify those children at highest risk for developing septic complications, such as meningitis.

Bacteriological Techniques

Antibody to cell wall glycolipid of Gram-negative bacteria: induction of immunity to bacteremia and endotoxemia.

Antiserum to the core glycolipid of gram-negative bacteria was prepared by immunization of rabbits with vaccine composed of killed cells of the uridine diphosphate galactose-deficient mutant (J5) of Escherichia coli O:111. Antiserum to J5 not only prevented death of animals from endotoxin but also prevented the local and generalized Shwartzman reactions. Antiserum to endotoxin also prevented renal cortical necrosis and disseminated intravascular coagulation during the evolution of the generalized Shwartzman reaction. Antiserum to be J5 mutant was successful in the treatment of overwhelming bacteremia produced by other gram-negative bacteria; in addition to bacteremia cause by coliform organism, antiserum to J5 was dramatically effective in treatment of bacteremia due to Pseudomonas aeruginosa. One injection of rabbit antiserum to J5 improved the survival rate from 15% in controls to 59% in treated animals (P less than 0.002). Active immunization with J5 vaccine was even more effective against pseudomonas bacteremia: such immunization improved the survival rate from 13% in controls to 92% in vaccinated rabbits. Since an antiserum effective against the J5 mutant of E. coli can be prepared safely in human subjects, such immunotherapy should be considered for patients with gram-negative bacteremia.

Animals

Nitroblue tetrazolium and Limulus assays for bacteremia after dental extraction: effect of topical antiseptics.

Bacteremia that occurs after dental extraction is common. This study assessed the effect of topical antisepsis on the incidence and magnitude of post-extraction bacteremia. On hundred patients scheduled for elective tooth extraction were randomized among four groups: contr-l, mouthrinsing with sodium-p-toluene sulfonchloramide (chloramine-T), toothbrushing with chloramine-T, and irrigation with Lugol's solution. The results showed that 84% of the control group and 59% of the treatment groups had positive blood cultures (290 organisms isolated) after dental extraction. The duration and magnitude of these bacteremias were diminutive as documented by the six serial blood cultures taken for each patient, colony counts per milliliter of blood, and nitroblue tetrazolium and Limulus assays. Brushing the teeth or rinsing the mouth with chloramine-T before dental extraction significantly reduced the incidence of bacteremia (P less than .025) and the number of different organisms recovered from each patient (P less than .05). Thus, topical treatment with chloramine-T is a simple and effective means of reducing the incidence of postextraction bacteremia.

Adolescent

A comparison of immunologic profiles and their influence on bacteremia in surgical patients with a high risk of infection.

Prospective sequential studies of the antibacterial function of neutrophils, lymphocyte responsiveness, opsonic capacity of serum and serum levels of C3(B), properdin, factor B, IgG, and albumin were made in 32 patients with severe burn injury (greater than or equal to 45%), 21 patients with severe multisystem traumatic injury, 20 high-risk, infected patients, and 22 renal transplant patients. Fifty-five episodes of bacteremia occurred in 37 of the 95 patients. Abnormal neutrophil function was clearly associated as a predisposing factor to these episodes, whereas there was no association between bacteremia and low serum levels of C3, IgG, factor B, or properdin. C3, factor B, and IgG usually rose following bacteremia as acute phase proteins, but there was evidence of a consumptive opsoninopathy in 11% of episodes. Defective opsonization was associated with a high risk of bacteremia only when there was a coexisting abnormality of neutrophil function (88% of such patients became bacteremic). None of 27 nonburned patients tested with delayed hypersensitivity antigens responded normally, and there was regularly depression of lymphocyte responsiveness to phytohemagglutinin-A and concanavalin-A in a whole blood assay related to serum immunosuppressive factors, but poor responsiveness was not associated with bacteremia.

Adolescent

Transient bacteremia due to suction abortion: implications for SBE antibiotic prophylaxis.

The incidence and character of the bacteremia associated with elective suction abortion was investigated in volunteer subjects aged 19 to 35 years who were to undergo first trimester abortion by suction curettage. One hundred and forty-four blood cultures were obtained from thirteen pregnant and four non-pregnant (control) subjects matched for age. Transient bacteremia occurred during or soon after suction abortion in 11 of 13 (84.7%) study subjects. Four of these patients were bacteremic after bimanual pelvic examination, just prior to initiation of the abortion procedure. Seven others developed bacteremia temporally related to cervical dilatation and suction abortion. The bacteremia was intermittent in some, persistent in others, existed as long as one hour after the procedure, and was transient in all patients. Microorganisms isolated from the blood were all normal genital tract flora and were predominantly anaerobes, although alpha hemolytic streptococci were also recovered. Mixed bacteremia occurred in six patients. In contrast, blood cultures from four non-pregnant women were sterile. This study indicates that the systemic circulation-uterine cavity barrier is significantly disrupted during abortion by suction curettage permitting endogenous genital tract microorganisms to gain access into the bloodstream. These observations also suggest that there may be some risk of developing endocarditis during suction abortion in patients with cardiac deformities, and lend some support to the current practice of giving antibiotic prophylaxis to abortion patients with cardiac lesions which predispose them to endocarditis.

Abortion, Induced

Hospital costs and mortality attributed to nosocomial bacteremias.

Hospital patients with nosocomial bacteremia and matched hospital control patients without this infection were used to determine the excess hospital costs and mortality attributed to nosocomial bacteremias. Mortality was 14 times greater in patients with nosocomial bacteremia than in matched members of the control group with the same primary diagnoses. An itemized cost analysis, based on 81 case-control pairs, showed an average excess of approximately $3,600 in direct hospital costs for patients who had nosocomial bacteremias. It is estimated that only 24% of the total excess costs to these hospital patients are preventable. Patients with nosocomial bacteremia had an average hospitalization period that was 14 days longer than the average hospital stay for members of the control group.

Costs and Cost Analysis

Bacteremia in a community hospital: spectrum and mortality.

The problem of bacteremia was studied at our 500-bed community hospital during 1974-1975. All patients with positive blood cultures for clinically significant organisms were analyzed with respect to age, sex, host factors, type, dose, and time of institution of therapy with antibiotics, and mortality. Of 142 episodes of bacteremia, outcome according to underlying host factors showed that 12/15 died in the rapidly, fatal group, 12/24 died in the ultimately fatal group, and in the nonfatal group 25/103 died. Mortality for Gram-positive bacteremia was 37% (7/54) for Gram-negative bacteremia in the nonfatal group. In addition to underlying host factors, inappropriate antibiotic therapy also contributed to higher mortality in patients with gram-negative bacteremia.

Adolescent

Pseudomonas aeruginosa bacteremia in a dialysis unit. 11. Relationship to reuse of coils.

Blood for culture was obtained over a six week period from 17 patients undergoing long-term hemodialysis. Bacteremia was detected during 18 of 201 dialyses. Blood drawn during fifteen of these dialyses contained pseudomonas aeruginosa. Ten of the 17 patients (59 per cent) had a Pseudomonas bacteremia some time during the study. Only one patient was symptomatic. The frequency of positive cultures was related to reuse of coils. No cultures were positive until after the fifth use, but by the tenth use, 41 per cent of the dialyses were associated with bacteremia. All coils that were used repeatedly and 32 of 48 of those used only once, grew Ps. aeruginosa when filled with media and incubated. This suggests that the coils were inoculated during dialysis and that benzalkonium chloride, the sterilizing agent, was unable to eradicate this organism. With repeated uses, the number of residual bacteria in the coil became large enough to cause detectable bacteremia during dialysis.

Cross Infection

Clostridium septicum bacteremia. Its clinical significance.

The medical records of 59 patients with Clostridium septicum bacteremia were reviewed; 42 (71 per cent) of these patients had malignancies. One half had hematologic malignancies, and one half had solid tumors. Of the 21 patients with solid tumors, 14 (67 per cent) had cancer of the colon. Among these patients, the cecum was the most frequent site of malignancy. The cecum and distal ileum were the most probable portals of entry for C. septicum bacteremia among the 28 patients examined at autopsy. Patients admitted to the hospital with C. septicum bacteremia usually have fulminating clinical courses and, unless the appropriate antibiotics are administered soon after admission, the outcome is fatal. The results of this study demonstrate the high association of C. septicum bacteremia and malignancy, and the need for early recognition and therapy.

Adolescent

Activation of the properdin pathway of complement in patients with gram-negative bacteremia.

To determine the pathway used for activation of complement component C3, serum levels of components C1, C4, C2, C3, C5, C6, and C9 and two properdin factors, properdin and factor B, were measured in 42 patients with gram-negative bacteremia, in 19 of whom shock subsequently developed. Mean levels of the classical components C1, C4, and C2 in bacteremic patients in whom shock subsequently developed did not differ significantly (p greater than 0.05) from those of patients with uncomplicated bacteremia. Levels of properdin, factor B and C3, C5, C6, and C9 were significantly (p less than 0.05) decreased in patients with shock in comparison with those with uncomplicated bacteremia. Taken together, these findings are consistent with activation of C3 and the terminal complement sequence, C5-C9, occurring primarily by the properdin pathway, in patients with gram-negative bacteremia eventuating in shock. Biologically active products released during activation of C3-C9 may contribute to the development of shock.

Bacteria

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

Polymicrobic bacteriuria: significant association with bacteremia.

Current clinical practice states that a urine culture yielding three or more isolates must be considered a contaminated specimen and discarded. The validity of this practice was tested by reviewing all patients at the West Haven Veterans Administration Hospital with positive blood cultures for 1 year to determine how many were associated with polymicrobic bacteriuria (two or more urine isolates each present at greater than 10(5) colonies/ml). During 1973 there were 18 patients who had bacteremia associated with a urinary tract infection in which the same organism with the identical antibiogram was found in both the blood and the urine of these 18 patients with monomicrobic bacteremia 11(61%) had polymicrobic bacteriuria, with a mean of an additional 1.75 urinary pathogens present in significant quantities. In these patients with polymicrobic bacteriuria, an indwelling bladder catheter was present for a mean period of 4.4 months before the episode of bacteremia. Only 5 of the 11 patients with polymicrobic bacteriuria had temporally associated urinary tract manipulation. Monomicrobic bacteriuria occurred in seven patients (39%). The mean indwelling bladder catheter time was 0.9 days, and urinary tract manipulation near the time of bacteremia occurred in all seven patients. Prospectively, nine other patients with polymicrobic bacteriuria were recultured by one of us to be certain that appropriate collection and transportation methods were used; the presence of polymicrobic bacteriuria was repeatedly demonstrated in 7(78%). This study illustrates the clinical importance of polymicrobic bacteriuria.

Aged

Anaerobic bacteremia as observed in a children's hospital. Clinically this may signify true anaerobic sepsis.

To ascertain the significance of anaerobic bacteremia in a children's hospital, the records of all patients whose blood cultures grew anaerobes during a 24-month period were reviewed. Anaerobes were isolated from 144 out of 1,126 blood cultures yielding bacteria. Anaerobic diphtheroid grew in 122 out of 143 anaerobic cultures, but only 4 out of 122 were isolated from patients with anaerobic sepsis. Nine per cent of the total episodes of anaerobic bacteremia occurred in 13 children who met out criteria for anaerobic sepsis; two oor more blood cultures obtained within a three-day period growing anaerobic bacteria, or an aerobe and an anaerobe, in a febrile child or one with an apparent infectious focus. Bacteroides accounted for 7 out of 13 (64 per cent) of the relevant isolates, while anaerobic diphtheroids 4 out of 13 (26 per cent) and anaerobic gram-positive cocci accounted for the remainder 2 out of 13 (18 per cent). Only one infant, with polymicrobial bacteremia, died, suggesting that anaerobic bacteremia is associated with less mortality in children than in adults. Anaerobic sepsis occurred in children who have had recent abdominal surgery, or who are immunosuppressed.

Adolescent

Bacteremia during barium enema study.

The occurrence of bacteremia was studied in patients undergoing barium enema. Blood cultures were done on 34 patients before, during, and after the procedure using two schedules. Cultures were obtained once during the procedure in the first schedule and four times in the second. None of the cultures were positive by the first schedule, while 23% of patients studied by the second schedule had one or more positive cultures. Organisms isolated were anaerobes. The bacteremia was transient and self-limited, without serious clinical sequelae. The incidence of bacteremia during barium enema examination was statistically indistinguishable from bacteremia previously reported during colonscopy. It is concluded that antibiotic prophylaxis is not indicated in most patients undergoing colonic diagnostic procedures. Prophylaxis in selected high-risk patients requires further study.

Adult