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Biomedical subjects

J N Sheagren

Publications and source records attributed to J N Sheagren.

At least 37 records · Page 2Linked to original sources
PubMed1985

Staphylococcal infections of the skin and skin structures.

A review of the pathogenesis, clinical manifestations, diagnosis, and therapy of staphylococcal skin and skin structure infections begins with discussion of the staphylococcal carrier state. Patients carrying Staphylococcus aureus are particularly vulnerable to infection if their skin is broken by wounds or placement of intravenous lines or catheters. S. aureus begins the process of infection by binding tightly to fibronectin-coated surfaces and endothelial cells; bacterial invasion, however, depends on the innate pathogenicity of the bacterial strain and on the status of the host's defenses. The carrier state may be manifested by recurrent infections in the skin and skin structures. Infection may be spontaneous, associated with skin trauma and/or presence of a foreign body, or related to the presence of bacteria. For diagnosis, appropriate samples of purulent materials are needed for Gram stain and culture. Drainage is absolutely essential. Most staphylococci are now penicillinase-producing. Initial coverage with a cell-wall-active agent combined with an aminoglycoside is usually highly effective. If a methicillin-resistant organism is suspected, vancomycin should be used. Treatment of the carrier state may eliminate recurrent episodes of staphylococcal skin infection. Meticulous infection-control procedures are extremely important in the prevention of staphylococcal infection of the skin and skin structures.

Carrier State↗
PubMed1985

Epidemiology and clinical significance of blood cultures positive for coagulase-negative staphylococcus.

Coagulase-negative staphylococci are frequently isolated from blood cultures. As these organisms may occasionally cause serious disease, differentiating bacteremia from contamination is very important but often difficult. Over a 26-month period, of 29,542 blood cultures processed at the University of Michigan Medical Center, 2,875 (9.7%) were positive, and of those, 694 (from 527 patients) grew coagulase-negative staphylococci. Isolates from the 439 patients with only one blood culture positive for coagulase-negative staphylococci and those from the 18 patients with two positive cultures 10 days or more apart were deemed contaminants. Review of the records of the remaining 70 patients with multiple isolates indicated that 33 had had an episode of true bacteremia, 29 (87.9%) of which were associated with intravascular catheters or prosthetic valves. Overall, 85% of all coagulase-negative staphylococci isolated during the study period were judged to be contaminants. Seventy-one percent of the blood cultures drawn during the episodes of bacteremia were positive for coagulase-negative staphylococci as opposed to only 34% in the patients with contaminated cultures (p less than 0.01). Moreover, coagulase-negative staphylococci grew in both aerobic and anaerobic bottles in 85% of blood culture sets drawn during episodes of bacteremia, but in only 30% of the cultures thought to be contaminated (p less than 0.001). Growth of coagulase-negative staphylococci in less than 48 hours was also significantly associated with bacteremia (p less than 0.01). Antibiotic sensitivity patterns were not useful in differentiating bacteremia from contamination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Population dynamics of ingested Clostridium difficile in the gastrointestinal tract of the Syrian hamster.

The population dynamics of Clostridium difficile in the hamster gastrointestinal tract were studied after intragastric inoculation with organisms and a 51Cr tracer. Seventy-eight percent of spores germinated within the small intestine within 1 hr. Germinated spores and vegetative cells both showed two phases of elimination from the hamster cecum--an initial phase of rapid death that was not affected by antibiotic treatment followed by a phase of complete inhibition of multiplication. The latter phase of inhibition was not seen in antibiotic-treated animals and was thus attributable to the indigenous flora. The 51Cr tracer mixed well with cecal contents and was eliminated exponentially with a dilution rate constant ranging from -0.46/hr to -0.31/hr in normal hamsters. The hamster cecum was therefore dynamically analogous to a continuous flow system, a finding supporting the concept that anaerobic continuous flow cultures are useful in vitro models of the cecal ecosystem.

Animals↗
PubMed1984

Treatment of skin and skin structure infections in the patient at risk.

Infections of the skin and skin structures in patients at risk can be either primary or secondary. In the normal host, the most important primary dermal pathogens are the group A beta-hemolytic Streptococcus and Staphylococcus aureus. These organisms can spread rapidly and seed to distant sites. Secondary skin involvement occurs in several life-threatening bacteremic conditions in previously normal hosts, especially in those involving meningococci and S. aureus. In the compromised host, although the acute pyogenic bacteria just mentioned can be even more devastating, low grade pathogens or nonpathogenic members of the normal flora, or both, are commonly involved. Such organisms include gram-negative aerobic bacilli, a variety of anaerobes, several fungi, and the herpesviruses. Therapy of primary skin and skin structure infections invariably should include debridement along with antibiotic coverage. Debridement must be complete, opening all deep extensions of the primary infection and removing, to the extent possible, all foreign materials. In the normal host, antibiotic coverage must include a beta-lactamase-resistant antibiotic or vancomycin if beta-lactamase-resistant, antibiotic-resistant S. aureus could be involved. In the compromised host, signs of local inflammation may be reduced; yet, debridement must still be aggressive and antibiotic coverage broad. Neutropenic patients should be covered for Pseudomonas aeruginosa, requiring a combination of an antipseudomonal agent plus an aminoglycoside. Antifungal or antiviral therapy, or both, should be added in the severely compromised host in the proper setting, especially in patients not promptly responding to antibacterial measures. Attempts to enhance host defenses should be considered.

Anti-Bacterial Agents↗
PubMed1983

Staphylococcus saprophyticus: role in urinary tract infections in men.

We investigated the role of Staphylococcus saprophyticus in urinary tract infections in men. Of 9,314 urine specimens cultured from men in a veterans hospital only 3 (2 patients) yielded Staphylococcus saprophyticus. Thus, Staphylococcus saprophyticus rarely causes infection in older men and should not be sought routinely by microbiology laboratories in hospitals serving men primarily.

Humans↗
PubMed1983

Antagonism of toxigenic Clostridium difficile by nontoxigenic C. difficile.

Cefoxitin-treated hamsters were first colonized with a nontoxigenic strain of Clostridium difficile, and then a toxigenic strain of C. difficile was administered. Toxigenic C. difficile was suppressed to a mean cecal population level of less than 0.2% of that found in control animals given only toxigenic C. difficile after cefoxitin treatment. Colonization with nontoxigenic C. difficile before toxigenic C. difficile was associated with 93% survival, as opposed to 21% survival of the control animals. Simultaneous administration of nontoxigenic and toxigenic C. difficile did not lead to suppression of toxigenic C. difficile and conferred no protection. These results are in keeping with previously established concepts of bacterial interactions on body surfaces and may have therapeutic implications.

Animals↗
PubMed1981

Antibody levels to bacterial peptidoglycan in human sera during the time course of endocarditis and bacteremic infections caused by Staphylococcus aureus.

Sera from patients with endocarditis and bacteremia due to Staphylococcus aureus were compared for peptidoglycan-binding capacity with those from normal blood donors. Those patients treated with beta-lactam antibiotics had higher antigen-binding levels than normal donors and patients treated exclusively with vancomycin (P less than 0.01). The factor responsible for this activity was purified by affinity chromatography from a normal donor and shown to be an immunoglobulin. Specificity studies indicated that the immunodominant determinant was a peptide sequence found in peptidoglycan precursors. Since soluble peptidoglycan molecules having the precursor peptide sequence are known to be secreted by some gram-positive bacteria like Micrococcus luteus when grown in the presence of beta-lactam antibiotics, these soluble molecules may constitute the "natural" immunogen. Such a hypothesis is consistent with the study of the peptidoglycan-binding capacities in the sera of these patients during the course of treatment. For most of the responding patients studied (four of four with bacteremia and seven of nine with endocarditis), a significant increase in peptidoglycan-binding capacity was observed in sera taken 1 to 5 weeks after the initiation of beta-lactam antibiotic therapy (compared with the initial serum studied). No such increase in the peptidoglycan-binding capacity over a similar time span was noted in the sera of people not receiving beta-lactam antibiotics (none of seven).

Anti-Bacterial Agents↗
PubMed1981

Technical aspects of the Staphylococcus aureus teichoic acid antibody assay: gel diffusion and counterimmunoelecrophoretic assays, antigen preparation, antigen selection, concentration effects, and cross-reactions with other organisms.

Because variable results are being reported from laboratories performing the teichoic acid antibody assay in patients with serious infections due to Staphylococcus aureus, we have thoroughly reviewed all technical aspects of the test. This paper reports on the importance of agar and antigen preparation in standardizing results of the assay and reducing the prevalence of false-negative and -positive tests. Once standardized, the counterimmunoelectrophoretic method is as accurate as the gel diffusion method for both initial screening and generating titers; practically, however, unless numerous tests are to be performed, the gel diffusion technique will suffice for most purposes. The cell wall of the Lafferty strain of S. aureus was used as the standard antigen in assays for serum antibodies. We studied whether it is an appropriate antigen and found that antibody titers obtained with the Lafferty strain antigen were, in three patients with endocarditis, the same as those obtained with antigens from the individual blood stream isolates. We have also confirmed that pooled human gamma globulin can be used, by back titration against newly prepared lots of antigen, to select optimal antigen concentration and is as good as more specific, higher titer serum specimens for that purpose. Finally, cell wall antigens from Staphylococcus epidermidis and a variety of streptococci may react with normal human sera, but such antigens are distinct by immunoprecipitation from those from S. aureus.

Antibodies, Bacterial↗
PubMed1981

Impaired concanavalin A-inducible suppressor T-cell activity in active alcoholic liver disease.

To examine the possible contribution of cellular immunoregulatory mechanisms to the pathogenesis and progression of alcoholic liver diseases, suppressor T-cell function was evaluated in patients with severe active or inactive alcoholic liver disease and compared with normal control subjects. Suppressor T-cell activity after in vitro induction by concanavalin A or other T cell-mediated immune reactions was then assessed. T-cell interactions studied included the proliferative responses of both autologous or allogeneic responding peripheral blood mononuclear cells to T-cell mitogens and to allogeneic cells. No significant differences were found in the ability to induce suppressor T cells between controls and patients with inactive alcoholic liver disease (p < 0.05). In contrast, T cells from patients with severe active alcoholic liver disease failed to develop suppressor cell activity (p < 0.001) after concanavalin A stimulation; restoration of suppressor cell function was found after these patients improved clinically. Adherent cells (monocyte-macrophages) from patients with active alcoholic liver diseases exhibited normal support of concanavalin A-induced blastogenesis and suppressor T-cell generation. This immunoregulatory cell abnormality could be important in the pathogenesis and/or progression of active alcoholic liver disease.

Adult↗
PubMed1981

Variability in the degree of opsonization and phagocytosis of strains of Staphylococcus aureus isolated from patients with disseminated intravascular coagulation.

Patients with septicemia due to Staphylococcus aureus occasionally manifest DIC. We studied the ability of organisms isolated from 30 patients with S. aureus (5 with DIC) to be opsonized and phagocytosed by normal human PMNs in the presence of normal human serum chelated with MgEGTA as a possible measure of alternative complement pathway activation. By this assay, nine S. aureus strains were found to be opsonized at 50% level or greater. Five of those organisms were isolated from the five patients who had clinical and laboratory manifestations of DIC, three of whom died. Patients from whom the other four activating strains were isolated were more seriously ill (by a method of grading clinical severity of disease) than the remaining 21 patients. Four of the nine patients from whom activating strains were isolated died compared to only four of the other 21 patients. The accelerated phagocytosis of staphylococcal strains from patients with DIC after incubation in MgEGTA-chelated serum suggests that surface factors on these strains interacted with serum factors differently than did strains from patients not developing DIC. However, all (except one) staphylococcal strains, from patients both with and without DIC, depleted hemolytic complement activity in MgEGTA-chelated serum; therefore a direct relationship between activation of the alternative complement pathway and opsonization seems not to exist. Thus strains of S. aureus capable of being opsonized by PMNs in human serum chelated with MgEGTA were associated with more severe infections often associated with DIC.

Disseminated Intravascular Coagulation↗
PubMed1980

Rapid identification of Staphylococcus aureus by using lysostaphin sensitivity.

Lysostaphin sensitivity was evaluated as a rapid screening test to differentiate Staphylococcus aureus from other species of staphylococci and micrococci. A total of 168 strains of staphylococci, 108 of which were S. aureus, were cultured overnight in brain infusion broth. Gram stains were peformed before and after a 1:10 dilution of the culture was exposed to 2 micrograms of lysostaphin per ml at 37 degrees C for 30 min. A reduction of 90% or greater in the number of organisms seen on comparison of the pre- and posttreatment Gram stains was considered a "positive" test result and was found in 106 of 108 S. aureus strains; 60 of 60 non-S. aureus staphylococci had a negative test result, showing no difference between the pre- and posttreatment Gram stains. Identical results were obtained using commerical blood culture media in place of brain heart infusion broth. Also studied prospectively were 100 blood or broth cultures which the clinical microbiology laboratory identified as containing gram-positive cocci suggestive of staphylococci. All 33 cultures later found to contain S. aureus gave positive test results; 67 of 67 non-S. aureus staphylococci, micrococci, and steptococci were negative.

Cell Wall↗