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Biomedical subjects

L Dall

Publications and source records attributed to L Dall.

At least 19 recordsLinked to original sources

Molecular characterization and LD(50) identify virulent isolates of Staphylococcus epidermidis from adult sepsis.

Staphylococcus epidermidis plays an important role in infections of patients with implanted prosthetic devices. The exact clinical significance of recovered S. epidermidis from clinical specimens is difficult to assess, as they are inhabitants of the normal skin. In this study, 11 adults with clinical sepsis and blood cultures that grew only S. epidermidis were the host population. Bacterial virulence in vivo was determined by using the mouse LD(50) assay where the intravenous lethality was determined for each patient isolate. Bacterial dose (CFU x 10(9)) that produced lethality in 50% of the animals at 12 h was the value used for comparison. Restriction fragment length polymorphism (RFLP) analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE) was used for identification of individual strains and their clonal organization. Confirmation of species assignment was done by RFLP analysis of 16S + 23S rRNA gene regions (ribotyping). Plasmid profile analysis was also conducted. Four of 11 blood isolates from adults with S. epidermidis sepsis had indistinguishable or closely related DNA patterns and were considered clone A. The same clone was previously seen to account for the majority of sepsis in a neonatal intensive care unit. There were significant differences in virulence characteristics of the S. epidermidis isolates. Clone A isolates produced lethality by LD(50) in mice at a dose averaging 2.35; clone B isolate at a dose of 2.54, and the remaining isolates, representing six distinct clones, were lethal to mice at significantly larger doses (3.51-5.17, average 4.16). These data suggest that individual clones of S. epidermidis isolated from septic adults have detectable differences in virulence as defined by an animal bioassay, and the more virulent clone is widespread.

APACHE↗

Beta-blocker use in patients with acute myocardial infarction treated by hospitalists.

It is well recognized that the administration of beta blockers to patients after myocardial infarction improves survival. This retrospective cohort and prospective study sought to define the usage of a large hospitalist group and enhance this usage by education and the utilization of a uniform discharge summary. All patients with a discharge diagnosis of acute myocardial infarction were included for analysis. The use of beta blockers by the hospitalist group was initially collected retrospectively and compared with two large cohorts. The data were presented to the hospitalist group. Prospective data collection then commenced. Retrospective analysis of the use of beta blockers showed a rate of 68% as compared with 21% and 34% in two large cohorts (P < .0001). After data were reviewed and conference occurred, prospective use of beta blockers increased to 90% (P < .0005). Patients with myocardial infarction were extremely likely to be treated with beta blockers by this hospitalist group. Review of previous usage and review of contraindications along with the use of a uniform discharge summary resulted in a significant increase in the use of these life-saving drugs.

Adrenergic beta-Antagonists↗

A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease.

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.

Adult↗

Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology.

Histoplasmosis is a common opportunistic infection in patients with human immunodeficiency virus (HIV) infection who reside in areas where Histoplasma capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV-Infected patients in Kansas City from October 1990 through March 1993 to define the incidence-specific risk factors, and pathophysiology of histoplasmosis. The annual incidence of histoplasmosis was 4.7%; 74% of the patients with histoplasmosis were symptomatic (all of whom had disseminated disease). A history of exposure to chicken coops, a positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count of < 150/microL were associated with an increased risk for histoplasmosis. Histoplasmin reactivity and the presence of pulmonary calcifications were not useful markers for patients at high risk. Symptomatic infection occurred in 9.9% of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients without documented prior exposure, and in 3.0% of patients who were anergic; these findings suggest that the pathophysiology of histoplasmosis in patients with AIDS involves reactivation of latent infection in some cases and dissemination of exogenously acquired infection in other cases.

AIDS-Related Opportunistic Infections↗

Contribution of the host to test results in assays of Staphylococcus epidermidis.

From two human populations (one pediatric and one adult), clinically diagnosed with Staphylococcus epidermidis (S. epidermidis) sepsis of similar severity, bacteria were isolated from pre-antibiotic blood samples and evaluated for virulence. The LD50 of the bacteria in a mouse model was performed, with evaluation of animals dying acutely following intravenous S. epidermidis administration. More simple assays of virulence were also performed, including bacterial adherence to a fibrin clot and carbohydrate specific lectin binding. The eight pediatric-host S. epidermidis isolates required a significantly larger dose to produce lethality in dosed animals (LD50) when compared to the 20 adult-host S. epidermidis isolates. The fibrin clot assay, a test that has corroborated bacterial virulence in endocarditis models, did not differentiate the groups: all but one of the 28 isolates were well above the adherence seen with the ATCC control, suggesting endocarditis-producing potential. Glycocalyx (slime) from eight of the more virulent isolates showed reactivity with a glucose-specific biotinylated lectin which was lacking in other isolates. Necropsy of mice dying at 12 hr showed S. epidermidis strain differences in specific organ effects. Overall, this study demonstrates the utility of the LD50 to provide a highly sensitive quantification of bacterial virulence. Necropsy of test animals dying acutely has showed an apparent organ tropism of some of these isolates which are usually considered harmless commensals.

Adult↗

Bacterial characterization in Staphylococcus epidermidis septicemia.

An analysis of the in vitro characteristics of Staphylococcus epidermidis strains isolated from patients with true S. epidermidis septicemia was undertaken. From a potential population of 921 cultures from adult patients with coagulase-negative bacteremia, highly defined selective criteria limited the population to 20 patients with S. epidermidis sepsis, from whose blood cultures the study organisms were isolated. Another population of 11 S. epidermidis blood isolates, clinically determined to be contaminants, were tested as a control group. In vitro assays performed on all isolates included slime quantification, hydrophobicity, surface hexoses, and capsule presence. Murine spleen phagocytosis of intravenously administered isolates was measured in vivo. The assayed quantity of cell-associated bacterial hexose sugars positively correlated with organism virulence to the host (p = 0.02). This bacterial population was also low in slime but varied as to the presence of capsule and ease of phagocytosis. Permanent catheter-bearing patients' bacteria were somewhat more hydrophobic (p = 0.07). We conclude that in vitro assays can differentiate bacteremic cultures from contaminants and that the characteristic that best relates to host toxicity in these S. epidermidis isolates was bacterial cell surface-associated carbohydrate.

Adult↗

Clindamycin effect on glycocalyx production in experimental viridans streptococcal endocarditis.

Abundant glycocalyx production by viridans streptococci in the rabbit model of endocarditis has been associated with delayed antimicrobial sterilization. Enzymatic digestion of the glycocalyx with dextranase enhances antibiotic activity. The effect of clindamycin (30 mg/kg, subcutaneous, three times daily) was studied in rabbits with experimental aortic valve endocarditis caused by high glycocalyx-producing viridans streptococci. Animals receiving clindamycin had smaller vegetations that were sterilized more quickly than did controls or animals receiving penicillin or dextranase alone (P less than .001). Penicillin plus dextranase treatment allowed greater bacterial killing than penicillin alone and did not differ significantly from clindamycin treatment. Electron micrographs revealed markedly less cell-adherent glycocalyx on organisms grown in vitro treated with clindamycin versus penicillin and controls. It is hypothesized that clindamycin inhibits glycocalyx production in vivo, allowing better antimicrobial penetration in the infected cardiac vegetation.

Animals↗

Quantitative assay of glycocalyx produced by viridans group streptococci that cause endocarditis.

A quantitative method to determine glycocalyx production by strains of viridans group streptococci from patients with endocarditis is presented. There is good correlation between this new tryptophan quantitative assay and qualitative assays employing polysaccharide stains (ruthenium red, periodic acid-Schiff, and Cellufluor) or the Molisch test. The quantification of the glycocalyx production in glucose substrate in vitro by viridans group streptococci correlates with the size of cardiac vegetation and ease of antimicrobial sterilization in experimental endocarditis. The relationship of in vitro quantification of glycocalyx to maintenance of infection, morbidity of infection, and antimicrobial treatment is discussed.

Animals↗

Septicaemia in a granulocytopenic patient caused by Corynebacterium striatum.

A 64 year old woman with metastatic endometrial carcinoma was admitted to the hospital after three grand mal seizures. Blood cultures yielded Corynebacterium striatum. The patient responded to parenteral ampicillin therapy. This is believed to be the first case of sepsis caused by this organism.

Agranulocytosis↗

Influence of underlying disease process on the utility of cellulitis needle aspirates.

A prospective microbiological evaluation of 87 patients with acute cellulitis was performed. Adult patients with cellulitis with diabetes mellitus or malignant disorders had a greater frequency of positive cultures. Qualitative leukocyte disorders associated with these underlying disease states was hypothesized as a contributing factor to this higher yield.

Acute Disease↗

Infective endocarditis of a bicuspid aortic valve caused by Hansenula anomala.

Infective endocarditis due to Hansenula anomala developed on a bicuspid aortic valve in a 40-year-old man. H. anomala, an ascomycetous yeast, may be a member of the normal flora of the throat and alimentary tract in humans but has not been previously known to be pathogenic in humans. A past history of intravenous drug use may have contributed to the development of disease in this patient.

Adult↗

Enzymatic modification of glycocalyx in the treatment of experimental endocarditis due to viridans streptococci.

The presence of abundant surface polysaccharide, or glycocalyx, on viridans streptococci has been associated with failure to eradicate the organism from experimental cardiac vegetations during penicillin treatment. The role of glycocalyx in retarding sterilization was tested by in vivo administration of dextranase, an endohydrolase that attacks internally situated alpha (1-6) linkages. Dextranase and penicillin, either singly or in combination, were used to treat experimental endocarditis. After two days of therapy, 100% of animals treated with penicillin or dextranase alone had infected vegetations, whereas only 25% treated with penicillin and dextranase had infected vegetations (P less than .01). After five days of therapy, 100% of the animals treated with penicillin had infected vegetations, versus none that were treated with penicillin and dextranase (P less than .01). We conclude that glycocalyx acts to retard antibiotic activity in vegetations and that partial enzymatic digestion of the glycocalyx facilitates penicillin sterilization of the infected valve.

Animals↗