Treatment of gram-negative bacteremia with antiserum to core glycolipid II. A controlled trial of antiserum in patients with bacteremia.
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Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.
Comparisons of O- and K-antigenic types and serum sensitivity were carried out with 149 strains of Escherichia coli isolated from adults with bacteremia and 46 strains from neonates with bacteremia. O-antigenic types O6, O4, O2, O16, O18, and O7 were observed most frequently, but their relative prevalence did not differ materially between adult and neonatal bacteremias. A greater proportion of strains from neonatal bacteremia contained K1 antigen and were autoagglutinable compared with strains from adult bacteremia, although K1 was the most frequent K antigen found in strains from adults. K-antigen-containing strains did not appear to be associated with enhanced severity of bacteremia, but nontypable strains, auto-agglutinable strains, and strains of O-antigenic types O4, O6, and O8 were associated with a greater frequency of shock and fatal outcome in adults. No differences could be detected between the serum sensitivities of E. coli isolated from adult bacteremia and those from neonatal bacteremia. K antigen did not affect serum sensitivity, but E. coli strains of O types O18, O2, O4, and O7 were more serum-resistant than other E. coli. Bacteremia caused by serum-sensitive E. coli was less often associated with shock and death than bacteremia caused by serum-resistant E. coli.
Escherichia coli K1 strains, isolated from human newborns with meningitis, were fed to pathogen-free Sprague-Dawley infant rats by an oral gastric tube. Feeding of 10(3) to 10(11) organisms colonized the intestine of approximately 70% of the animals. At 5 days postfeeding of 3- to 5-day-old rats, bacteremia was detected in 60%, and meningitis occurred in 15% of bacteremic animals. Colonization and bacteremia were age-related. Rats 15 days old had only 19 colonization and 10% bacteremia, and those 30 days old were almost completely resistant to colonization and bacteremia. The intranasal route was less effective in inducing colonization and bacteremia. Intralitter transmission from E. coli K1-fed rats occurred, with 52% of water-fed controls becoming colonized and 15% become bacteremic. Colonization of mothers from their fed infants occurred, but none of five tested developed bacteremia. Other E. coli capsular polysaccharide types were studied. A K92 strain isolated from a newborn with meningitis induced a 77% colonization rate, and 8% of these developed bacteremia without detectable meningitis. An E. coli K100 strain showed a 32% colonization rate, and 2% developed bacteremia. The age relation, relatively high virulence of K1 compared with other capsular types, spontaneous appearance of colonization, bacteremia, and meningitis, and intralitter transmission of colonization and disease in newborn rats closely parellel E. coli epidemiology in human neonates.
One hundred fifteen episodes of bacteremia occurred among 2790 children with malignancies hospitalized during a 45-month period. The mean age was 9.3 years with a male predilection (62%). A greater (p less than .025) number of children over 10 years of age died with bacteremia when compared to younger children. The majority of episodes occurred in children with leukemia (56%); however, once bacteremia developed, a significantly (p less than .05) greater number of children with lymphoma died when compared to children with other malignancies. Absolute polymorphonuclear leukocyte counts were greater in survivors (p less than .025) than in children who died. Thirty-seven different microorganisms were isolated with E. coli, S. Aureus, P. aeruginosa, and K. pneumoniae accounting for 50% of the episodes. Anaerobes were isolated from blood of 12 (10%) children. Twelve children had polymicrobial bacteremia and 14 had recurrent bacteremia which occurred during antibiotic therapy. Mortality (78%) in these children was significantly (p less than .001) greater then in children from whom one microorganism was isolated (47%). Interesting aspects include the resurgence of S. aureus, failure of development of meningitis in children with bacteremia, and unchanged antibiotic susceptibility since the last review of bacteremia in this institution. Polymicrobial and recurrent bacteremia necessitate obtaining simultaneous and sequential blood cultures to facilitate administration of appropriate antimicrobial therapy until bone marrow function improves.
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.
Six cases of Providencia bacteremia occurring between 1969 and 1978 were reviewed. These cases represented 3% of the gram-negative bacteremias occurring at one hospital. All six cases of Providencia bacteremia were secondary to urinary tract infection with P. stuartii, and in most the infection developed only shortly before the onset of bacteremia; in three cases the bacteremia developed immediately following manipulation of the urinary tract. Patients with long-standing Providencia infections did not acquire bacteremia. The signs and symptoms of Providencia bacteremia were typical of those of septicemia except that vascular collapse was not a prominent feature, occurring in only one patient. The mortality was 33%. All the Providencia strains cultured from the bloodstream were susceptible to gentamicin, although the frequency of gentamicin resistance increased from roughly 10% to 50% during the period studied; the increase in gentamicin use over this period was more gradual. Also noted was a decrease in resistance to ampicillin that paralleled a decrease in ampicillin use. All the Providencia strains were susceptible to amikacin.
The potential consequences of bacteremia are considerable in all infants but particularly in those from 3 to 24 months of age with temperatures of 38.3 degrees C or more. Physicians have been advised to scrutinize these patients carefully with a variety of diagnostic tests and to treat their conditions vigorously if bacteremia is seriously considered or proved. We undertook to determine how often primary care pediatric practitioners encounter such patients "at risk" for bacteremia. Among the practices of nine pediatricians in Monroe County, New York, involving 220 practice days throughout 1977 and 4,151 patient visits, we found 145 instances of potential bacteremia. Depending, then, on the season of the year, practitioners may face this diagnostic and management dilemma as often as once each day. Therefore, laboratory means for determining those infants at highest risk for bacteremia or for rapidly diagnosing bacteremia will need to be readily available to practitioners.
During a six-month period, 187 inpatients had bacteremia associated with community-acquired infection and 91 patients had bacteremia from a nosocomial infection. The most frequently identified sites of infection in both types of bacteremia were the respiratory and urinary tracts. Escherichia coli and Diplococcus pneumoniae were the organisms most frequently isolated from cultures of patients with community-acquired bacteremia, and E coli, Staphylococcus aureus, and Klebsiella were most frequently isolated from patients with nosocomial bacteremia. Bacteremic nosocomial infections were related to urinary catheters, respiratory and intravenous therapy, or hyperalimentation in 32 of the 91 cases. Even assuming the unproved hypotheses that rigid adherence to current guidelines would prevent all of these procedure-related cases, 59 cases of bacteremia would still have occurred. This emphasizes the need for further research into prevention of nosocomial infection.
Four local prophylactic methods were studied in the prevention of postextraction bacteremia: 1) mouth rinsing with 1% iodine solution, postoperative bacteremia frequency 55%, 2) operative field isolation with cotton rolls and saliva ejector, bacteremia frequency 34%, 3) operative field isolation and disinfection with 10% iodine solution, bacteremia frequency 32%, 4) operative field isolation and disinfection with 0.5% chlorhexidine solution, bacteremia frequency 13%. The operative field isolation together with local disinfection with chlorhexidine was recommended for routine practice. However, when dealing with known or suspected risk group patients, a combined systemic and local prophylactic method was strongly recommended, as this was found in previous investigation to be the most effective method for reducing the frequency of bacteremia.
Medical records of 134 patients with Staphylococcus aureus bacteremia at the Cincinnati General Hospital during 1975-1977 were reviewed. Bacteremia was community-acquired in 48 patients and hospital-acquired in 73 patients. In addition, 13 patients were on chronic hemodialysis. In 22 patients, bacteremia was associated with an infected intravenous catheter; all except one of these patients acquired the infection in the hospital. Thus 21 of 73 (29%) episodes of hospital-acquired S aureus bacteremia were associated with an infected intravenous catheter. Four of the 22 patients with intravenous catheter-associated bacteremia had endocarditis (18%). The overall incidence of endocarditis in this study was 16% (21 of 134 patients). This contrasted with the much higher incidence of endocarditis (64%) in Staphylococcal bacteremia reported from this same hospital in patients during 1940-1954. Possible reasons for this difference are discussed.
Polymicrobial bacteremia increased from 6% in 1970 to 13% in 1975 in patients with bloodstream infections. This type of serious infection most commonly complicated genitourinary (27%) and gastrointestinal (26%) conditions, frequently followed invasive procedures (68%), was more common in hospitalized patients (73%), and was often associated with malignancies (25%) or immunosuppressive or cancer chemotherapy (34%). Although polymicrobial endocarditis was more commonly encountered in recent years, this infection accounted for only 4.5% of patients with multiple organism bacteremias. Gram-negative aerobic bacteria were isolated from 62% and anaerobic bacteria in 39% of patients with polymicrobial bacteremia compared with 37% and 14%, respectively, in patients with monomicrobial bacteremia. In the 88 patients with polymicrobial bacteremia, the mortality was 44.5%, compared with 18.0% in patients with monomicrobial 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.
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.
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.
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.
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.
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.