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Biomedical subjects

W R McCabe

Publications and source records attributed to W R McCabe.

At least 55 records · Page 3Linked to original sources
PubMed1980

Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients.

Evaluation of 612 episodes of gram-negative bacteremia over a 10-year period demonstrated its progressively increasing frequency. This increase was associated with an increasing proportion of patients with more severe underlying disease, increasing patient age, increasing frequency of cardiac surgery and manipulative procedures, and increasing frequency of treatment with antibiotics, corticosteroids and antimetabolites in patients with bacteremia. Fatality rates paralleled the severity of the host's underlying disease as noted in previous reports. The urinary tract was the most frequent source of bacteremia, but in 30 per cent of the patients, predominantly those with more severe underlying disease, the original source could not be identified. Of all blood cultures obtained in these patients, 72 per cent were positive. Bacteremia was of low magnitude with 77 per cent of the patients have quantitative blood cultures with less than 10 gram-negative bacilli per milliliter of blood. Escherichia coli was the most frequent etiologic agent followed in frequency by Klebsiella-Enterobacter-Serratia species, Pseudomonas aeruginosa, Proteus and Providencia species, and species of Bacteroides. Sixteen per cent of the bacteremias were polymicrobic. K and O-antigen typing of Escherichia coli and capsular typing of K. pneumoniae demonstrated that a large number of serologic types of these strains were responsible for bacteremia. Over-all, bacteremia caused by multiple species of bacteria was associated with higher fatality rates, but no significant differences in fatality rates could be demonstrated for bacteremias caused by individual species of gram-negative bacilli when comparisons were made between patients with underlying diseases of similar severity. The presence or type of K-antigen did not influence the lethality of Esch. coli infections. Although some O-antigen types, 0:4, 0:6 and 0:8, were associated with higher fatality rates than other O-antigen types, "rough" or autoagglutinable Esch. coli were as lethal as smooth strains. These findings indicate that bacterial factors, other than antibiotic resistance, have little influence on the outcome of gram-negative bacteremia and that gram-negative bacilli function primarily as "opportunistic" pathogens.

Adolescent↗
PubMed1980

Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients.

Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIC) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underyling host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response greater than 99.6 degrees F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.

Adolescent↗
PubMed1980

Meningitis caused by gram-negative bacilli.

Thirty adults with meningitis caused by gram-negative bacilli were observed from 1968 to 1978 at four hospitals associated with Boston University School of Medicine. Equal numbers of two distinct types of gram-negative bacillary meningitis--spontaneously occurring meningitis and meningitis after neurosurgery--were found. Spontaneously occurring meningitis appeared to be caused most often by Escherichia coli and Haemophilus influenzae. Meningitis occurring after neurosurgical procedures was more insidious in onset, more protracted in course, and more often caused by organisms resistant to multilple antibiotics. Approaches to therapy are based on the differences in character of these two types of meningitis.

Adult↗
PubMed1980

Potential use of shared antigens for immunization against gram-negative bacillary infections.

The demonstration of common antigens shared by all Enterobacteriaceae has led to evaluation of the effects of immunization of animals and man with these antigens in protecting against bacterial infections and challenge with LPS. Both active and passive immunization with the Re mutant of S. minnesota and the J5 mutant of E. coli afforded significant protection to mice and rabbits against lethal challenge with viable bacteria and heterologous LPS. KDO appears to be the antigenic determinant responsible for induction of protective antibody after immunization with the Re mutant but the antigenic determinant of the J5 mutant has yet to be identified. Studies in volunteers indicate that human immunization with R mutants can be accomplished without excess adverse reactions and that such immunization may protect against Gram-negative bacillary infections.

Animals↗
PubMed1979

Adult bacteremia caused by gram-negative bacilli.

Because gram-negative bacteremia is increasing in frequency, it is important for physicians to suspect, carefully evaluate, and initiate early appropriate therapy. Identification of the probable source of bacteremia and a knowledge of the hospital microflora are helpful in guiding antibiotic selection. The mortality of gram-negative bacteremia tends to vary with the severity of the underlying disease and, accordingly, tends to be low in obstetrical patients. Prevention is the most effective method of controlling these infections and, therefore, care and discretion when employing invasive devices is essential. With the increasing incidence of these infections and the increased threat of antibiotic plasmid resistance, future infection control in high-risk patients by immunoprophylaxis may be necessary.

Anti-Bacterial Agents↗
PubMed1978

Escherichia coli in bacteremia: K and O antigens and serum sensitivity of strains from adults and neonates.

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.

Adult↗
PubMed1977

Cross-reactive antigens: their potential for immunization-induced immunity to Gram-negative bacteria.

The involvement of multiple species and serologic types in gram-negative bacteremia prompted evaluation of immunization with shared, cross-reactive antigens of gram negative bacilli. Active and passive immunization with Re chemotype mutants of Salmonella minnesota afforded significant protection against heterologous gram-negative bacilli and were considerably more effective than immunization with smooth S. minnesota or its Ra, Rb, Rc, Rd1 and Rd2 mutants. Since the lipopolysaccharide of the Re mutant is composed solely of 2-keto-3-deoxycotonate (KDO) and lipid A, the protective activity of antibody to the Re mutant and lipid A was evaluated. Immunization with Re mutant protected granulocytopenic rabbits against lethal bacteremia and protected mice against lethal challenge with heterologous endotoxins, whereas antibody to lipid A had no protective activity. In concomitant clinical studies, high titers of antibody to the Re mutant at the onset of bacteremia were associated with a significant diminution in the frequency of shock and death, which was independent of any effect of O-specific antibody.

Animals↗
PubMed1977

Immunization with R mutants of Salmonella minnesota. II. Comparison of the protective effect of immunization with lipid A and the Re mutant.

The protective effect of active immunization with Salmonella minnesota Re bacilli or lipid A was assessed in the granulocytopenic rabbit model. Animals were immunized with Re bacilli, lipid A, or Pseudomonas aeruginosa as a nonspecific immunogen. After colonization with one of three enterobacterial strains (two Escherichia coli, one Enterobacter aerogenes), the immunized rabbits as well as controls given saline injections were made leukopenic with nitrogen mustard and monitored for fever, bacteremia, and death. Survival rates were significantly greater in Re-immunized animals than in saline controls or P. aeruginosa-immunized animals. Immunization with lipid A afforded no protection. In addition, rabbits immunized with Re mutant bacilli developed bacteremia less frequently than the others, indicating that antibody to Re may inhibit invasion of the intestinal mucosa as well as protect after bacteremia has developed.

Animals↗
PubMed1977

Immunization with R mutants of Salmonella minnesota. II. Serological response to lipid A and the lipopolysaccharide of Re mutants.

Rabbits were immunized with Salmonella minnesota Re mutant bacilli or lipid A, and the serological responses were compared. Re lipopolysaccharide and lipid A were found to possess distinct antigenic determinants as measured by hemagglutination, hemolysis, and precipitin techniques. Lipid A preparations from several enterobacterial and non-enterobacterial species were shown to cross-react in agar gel precipitation reactions. In contrast, preparations from bacilli that do not contain glucosamine as an integral part of their lipid A structure did not demonstrate cross-reactivity with enterobacterial lipid A. Antibody to smooth heterologous bacilli present in some antisera prepared against Re bacilli or lipid A was directed specifically against the smooth lipopolysaccharide and not against the Re or lipid A determinants, demonstrating a nonspecific mitogenic response. Precipitation and immunofluorescence tests indicated that the Re determinant was available on smooth bacilli for reactions with specific antisera but that the lipid A determinant was not.

Animals↗
PubMed1976

Effects of IgM and IgG antibody in patients with bacteremia due to gram-negative bacilli.

Earlier studies, which indicated that high titers of O-specific antibody to the patient's infecting organism in acute-phase serum specimens were not associated with a decrease in the frequency of subsequent shock and death in bacteremia due to gram-negative bacilli, were reexamined for evaluation of the protective activity of specific IgG and IgM antibody. Titers of hemagglutination antibody and levels of IgM, determined by indirect immunofluorescent staining of the patient's infecting organism, as well as hemagglutination titers after reduction of serum with 2-mercaptoethanol and IgG levels, correlated closely (P less than 0.001). High titers of IgG antibody to the patient's infecting organism in acute-phase specimens were associated with a significant reduction in the frequency of shock and death in bacteremia. In contrast, high titers of IgG antibody were not associated with a diminution in the frequency of shock and death. The previously demonstrated protective activity of antibody to an antigen, Re lipopolysaccharide, shared by most gram-negative bacilli was reconfirmed and shown to be independent of the protective activity of O-specific IgG antibody.

Antibodies, Bacterial↗
PubMed1975

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↗
PubMed1975

The relation of K-antigen to virulence of Escherichia coli.

The content of K-antigen was determined for 100 strains of Escherichia coli isolated from the blood of patients with bacteremia. 30 strains isolated from urine cultures, and 30 strains isolated from the feces of patients recently admitted to the hospital. The K-antigen content of urinary isolates of E. coli was significantly greater than that of strains isolated from feces, as noted by other workers. In contrast, the amount of K-antigen of blood culture isolates was not significantly greater than that of fecal isolates and was significantly lower than that of urinary E. coli isolates. No correlation could be detected between the K-antigen content of blood culture isolates and the severity and outcome of the bacteremia.

Animals↗