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Biomedical subjects

D T Durack

Publications and source records attributed to D T Durack.

At least 127 records · Page 7Linked to original sources
PubMed1978

Effect of antibiotics on the prevention of experimental Bacteroides fragilis endocarditis.

The relative efficacy of single doses of antibiotics in modifying the development of Bacteroides fragilis subsp. fragilis endocarditis was studied in an experimental model. Antibiotics were administered 0.5 h before intravenous injection of B. fragilis subsp. fragilis into rabbits prepared by insertion of a polyethylene catheter into the left side of the heart; 48 h later, intracardiac vegetations were excised and cultured anaerobically. B. fragilis was recovered from 92% of untreated animals. After a single dose of procaine penicillin G (250 mg/kg intramuscularly), 80% of the animals remained infected. Chloramphenicol (30 mg/kg), carbenicillin (50 mg/kg), and metronidazole (10 mg/kg) were also ineffective (76, 80, and 75% infected, respectively). Cefamandole (30 mg/kg), cefoxitin (30 mg/kg), and erythromycin (30 mg/kg) were significantly more active (50, 55, and 45% infected, respectively), as were higher doses of carbenicillin. Clindamycin (50 mg/kg) was the most effective regimen (11% infected). At present, the relevance of these results to the therapy of serious B. fragilis infections is not known, but this model may prove useful in the evaluation of the prevention of B. fragilis subsp. fragilis bacteremia.

Animals↗
PubMed1978

Effect of immunization on susceptibility to experimental Streptococcus mutans and Streptococcus sanguis endocarditis.

It has been asserted that humoral immunity is an important potentiating factor in pathogenesis of infective endocarditis, in that prior immunization to certain bacteria may predispose the host to endocarditis caused by those organisms. If so, possible future vaccination of humans with streptococcal antigens for the prevention of dental caries might increase the susceptibility of the population to streptococcal endocarditis. To examine this hypothesis further, we immunized rabbits with killed Streptococcus sanguis or Streptococcus mutans. After complement-fixing antibody had developed, the rabbits were tested for susceptibility to experimental infective endocarditis. Rabbits with high titers of complement-fixing antibody to the infecting organism developed streptococcal endocarditis less often (13%) than animals with lower titers (69%; P less than 0.0002). These findings do not support the hypothesis that pre-immunization predisposes to infective endocarditis and lend no credence to the concept that vaccination of human subjects against dental caries might increase their susceptibility to streptococcal endocarditis. On the contrary, the results of these experiments indicate that specific antibody can confer relative immunity to infective endocarditis.

Animals↗
PubMed1977

Protective role of complement in experimental Escherichia coli endocarditis.

Fourteen strains of Escherichia coli were tested for ability to cause infective endocarditis in rabbits prepared by prior placement of an intracardiac catheter. Strains that were resistant to the bactericidal action of serum caused E. coli endocarditis in 91.4% of rabbits, whereas serum-sensitive strains usually failed to cause persisting infection (11.3% infected, P less than 0.001). Although serum-sensitive E. coli lodged on heart valves within 1 h after intravenous injection, they survived less than 24 h in most normal rabbits. In contrast to normals, all five C6-deficient rabbits injected with a serum-sensitive strain of E. coli developed infective endocarditis (P less than 0.005). No correlation was found between the presence of K1 antigen and the incidence of experimental E. coli endocarditis. Thus, the ability of strains of E. coli to establish persisting endocardial infection in rabbits appears to be directly associated with resistance to the complement-mediated serum bactericidal system. These findings may explain in part the rarity of gram-negative bacillary endocarditis in patients; they also indicate that in certain special circumstances the serum bactericidal system can play a decisive role in host defense.

Animals↗
PubMed1977

Functional studies on human peritoneal eosinophils.

A number of functional studies were performed on essentially pure eosinophil preparations obtained from the ascitic fluid of a patient with eosinophilic gastroenteritis. These cells responded to chemotactic factors including a bacterial factor, partially purified C5a, and factors generated from serum or ascitic fluid. The chemotactic activity generated in the patient's ascitic fluid was capable of attracting both neutrophils and eosinophils, was dependent on the presence of complement components, and was identified as C5a. Metabolic studies demonstrated that particle ingestion by eosinophils was associated with a marked increase in hexose monophosphate shunt activity ([1-14C]glucose oxidation), H2O2 formation ([14C]formate oxidation), superoxide anion generation, chemiluminescence, thyroid hormone degradation, iodination, and estrogen binding. This postphagocytic metabolic burst by eosinophils was qualitatively similar to that observed in neutrophils, but for several parameters the eosinophil response was greater than the neutrophil response.

Chemotaxis↗
PubMed1975

Experimental bacterial endocarditis. IV. Structure and evolution of very early lesions.

The vegetations of experimental sterile and bacterial endocarditis in rabbits were studied using light, immunofluorescent and electron microscopy. At an early stage, both lesions were composed chiefly of masses of platelets supported in a scaffolding of fibrin strands. In previous studies, this structure has often been described merely as "fibrin". After i.v. injection of Thorotrast, sterile vegetations showed remarkable accumulations of mononuclear phagocytes containing this substance, on surfaces projecting into the bloodstream. Sections fixed 30 min. after i.v. injection of streptococci also showed these phagocytes, which contained large numbers of bacteria. The possibility that BE is initiated by phagocytosis of circulating bacteria has been raised. Smaller numbers of circulating streptococci reached the vegetation by direct adhesion to exposed surfaces. In contrast, a majority of Proteus and Staphylococcus albus adhered directly to vegetations, without phagocytosis. Subsequently, these first settlers multiplied rapidly to form rounded colonies surrounded by capsules of fibrin, which apparently provided protection from phagocytosis. The vegetations grew by accretion of layers of fibrin and platelets, with colonies sandwiched between them. This suggested that a cycle of thrombosis and reseeding by circulating bacteria was a factor in their growth. Colonies showed morphological changes consistent with ageing after two days. Healing occurred by endothelialisation and organisation, and was greatly accelerated by penicillin treatment.

Animals↗
PubMed1975

Current practice in prevention of bacterial endocarditis.

A survey of Oxfordshire dentists showed that most practise prophlaxis of bacterial endocarditis, but that few follow currently recommended regimens. for example, prophylactic antibiotics are started one or more days before the procedure by 72 per cent of dentists, and two or more days before by 25 per cent. Eight-seven per cent administer antibiotics for a total of four or more days. Penicillin is most often given, but tetracyline remains the commonest second choice. Only 12 per cent use intramuscular drugs as first choice, and procaine penicillin is seldom used. These practices are contrasted with current medical recommendations and discussed with reference to fresh experimental evidence on prevention of bacterial endocarditis.

Administration, Oral↗
PubMed1975

Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

The ability of antibiotics to prevent Streptococcus sanguis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.

Ampicillin↗
PubMed1974

Chemotherapy of experimental streptococcal endocarditis. 3. Failure of a bacteriostatic agent (tetracycline) in prophylaxis.

Bacteriostatic agents are frequently recommended as alternatives to penicillin for prophylaxis of bacterial endocarditis. To test the efficacy of this group of antimicrobials, prophylaxis of experimental streptococcal endocarditis was attempted with tetracycline. The number of streptococci colonizing the aortic valves of rabbits was not affected by inhibitory levels of tetracycline, but multiplication was checked. Streptococcis urvived in vegetations for seven days despite the continuous presence of tetracycline, and multiplied when the drug was withdrawn. It is therefore suggested that bacteriostatic agents may be valueless for prophylaxis of bacterial endocarditis.

Animals↗
PubMed1974

Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin-sensitive streptococci.

Bacterial endocarditis was produced by intravenous injection of Streptococcus viridans into rabbits with preexisting sterile endocardial vegetations. After 6 h had elapsed, bacteria in the vegetations could not be eradicated by brief treatment with antimicrobials to which the streptococci were sensitive. However, when treatment with penicillin was continued for 4 days, the animals were cured. The 6-h infection therefore offered a model in which treatments could be conveniently compared over a short period. Synergism was demonstrated between penicillin and streptomycin in endocarditis due to a fully penicillin-sensitive streptococcus, a point which had not been previously proved in vivo. The clinical implications are discussed.

Animals↗
PubMed1973

Chemotherapy of experimental streptococcal endocarditis. I. Comparison of commonly recommended prophylactic regimens.

The effectiveness of various antibiotics commonly recommended for the prophylaxis of bacterial endocarditis has been evaluated in experimental streptococcal endocarditis in rabbits. High doses of penicillin G did not prevent the development of this infection. The only consistently successful prophylactic regimens using penicillin alone were those which provided for both an early high serum level and more than 9 h of effective antimicrobial action. Vancomycin was the only other drug which proved uniformly successful when given alone, even though the duration of its antimicrobial action in the blood was only 3 h. However, combined therapy using penicillin G or ampicillin with streptomycin was always effective in prophylaxis. Treatment with single injections of ampicillin, cephaloridine, cephalexin, clindamycin, cotrimoxazole, rifampicin, streptomycin, erythromycin, and tetracycline failed to prevent infection. The findings provide information on the effect of antimicrobials in vivo and may be applicable to the chemoprophylaxis of infective endocarditis in clinical practice.

Ampicillin↗