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Endotoxin-induced susceptibility to staphylococcal infection and its reversal by adrenergic blocking agents.

Sultzer, Barnet M. (Princeton Laboratories, Inc., Princeton, N.J.), and Henry H. Freedman. Endotoxin-induced susceptibility to staphylococcal infection and its reversal by adrenergic blocking agents. J. Bacteriol. 90:1001-1006. 1965.-The transient phase of increased susceptibility to bacterial infection in mice provoked by prior administration of small doses of endotoxin was investigated for possible mediation by vasoactive substances. Animals were given endotoxin intravenously shortly before intraperitoneal injection of Staphylococcus aureus Smith, thereby lowering the lethal inoculum 10-fold. To determine whether this susceptibility state could be obviated, mice were pretreated with phenoxybenzamine or dibenzylchlorethylamine. Mortality decreased from an average of 81% in the endotoxin control groups to about 23% in the treated mice, closely approximating the mortality in control mice injected with saline and staphylococci. Neither antiadrenergic agent independently altered the resistance of mice to a higher lethal staphylococcal challenge, nor did these materials induce extravascular leukocyte mobilization into the peritoneal cavity. The results suggest a possible role of vasoactive staphylococcal alpha-toxin, as well as epinephrine or epinephrine-like factors, in this altered state of resistance to staphylococcal infection.

Animals↗

Solid-phase radioimmunoassay for immunoglobulin G Staphylococcus aureus antibody in serious staphylococcal infection.

Clinical features of 99 patients with staphylococcal infection were reviewed, and sera were tested by solid-phase radioimmunoassay and gel diffusion for staphylococcal antibodies to ascertain whether these variables predict the extent of infection and the need for prolonged therapy. Clinical features, including the presence of a primary site of infection or a continuous pattern of bacteremia, were not sufficient for differentiating endocarditis or complicated bacteremia from uncomplicated bacteremia. Patients with uncomplicated bacteremia were cured by 3 weeks of antibiotic therapy. Positive serologic tests for staphylococcal antibody helped distinguish patients with endocarditis or complicated bacteremia from patients with uncomplicated bacteremia. Radioimmunoassay was more sensitive than gel diffusion for identifying patients with complicated bacteremia. Our results indicate that patients with a positive antibody result 14 days after the onset of infection should be considered to have endocarditis or complicated bacteremia, but a negative antibody result would support short-term antibiotic therapy.

Antibodies, Bacterial↗

[Chemotherapeutic effect of 3-(5-nitrofuryl)-7-(5-nitrofurfurylidene)-3,3a,4,5,6,7-hexahydro-2H-indazole in experimental staphylococcal infection].

Chemotherapeutic activity of 3-(5-nitrofuryl)-7-(5-nitrofurfuryliden)-3, 3a, 4, 5, 6, 7-hexahydro-2H-indazol (compound 26) was studied on albino mice with experimental staphylococcal infection. The animals were contaminated intraperitoneally. The results of culture of the specimens of the organs of the mice killed within various terms and the values of the spleen bacterial index served as the criteria of the effectiveness. Compound 26 was administered in doses of 20, 10 and 5 mg/kg once a day for 3 days. The treatment was started simultaneously with or 24 hours after the contamination. The results showed that compound 26 in a dose 20 mg/kg (0.4 mg/mouse) possessed high chemotherapeutic activity in experimental staphylococcal infection of albino mice and could be recommended for a thorough study as a potential agent for chemotherapy of staphylococcal infection.

Animals↗

[Controlled study of pristinamycin versus oxacillin in staphylococcal infections ].

A prospective double-blind study was conducted in patients hospitalized with a staphylococcal infection. The effects of oxacillin (4-6 g/d) and pristinamycin (2-3 g/d) were compared. These were 52 cutaneous infections and 17 other ones. The results of the two antibiotics effects were not different. Tolerance was appreciated in the 82 patients who entered the study: pristinamycin had fewer (but not significantly different) side effects than oxacillin (3/37 vs 9/45). As pristinamycin is active in vitro on at least 95 p. cent of strains, we concluded that it can be the first choice antibiotic in staphylococcal infections when the oral route is possible.

Administration, Oral↗

[The paradoxes of staphylococcal infection in dentistry].

Study of the role of staphylococcal infection in pyoinflammatory complications of mandibular injuries showed that immunization of this category of patients with staphylococcal antitoxin simultaneously with antibiotic therapy leads to a significant increase in the blood level of anti-alpha-toxin. The latter has a positive impact on the clinical course of disease and staphylococcal contamination of involved site and oronasal mucosa.

Adolescent↗

[Effect of an autovaccine on the course of an experimental staphylococcal infection].

The effect of autovaccine on the state of cellular immunity in mice with staphylococcal infection was studied. The maximum decrease of staphylococcal dissemination in internal organs, espeically in the lungs, as well as an increase in the intensity of phagocytosis by peritoneal macrophages were observed after the administration of the vaccine by the method of inhalation. The intranasal administration of the vaccine also proved to be more effective than subcutaneous injection. The cumulation of immune response was more pronounced after the aerosol administration of autovaccine, especially in cases of pathological processes in the respiratory organs.

Animals↗

[Protective action of remantadine in experimental influenzal-staphylococcal infection].

The effect of remantadine on the course of influenzal-staphylococcal infection was studied in white mice. When the drug was injected to the mice infected with remantadine-sensitive strain of influenza A virus and Staphylococcus the lethality decreased from 93.3% to 26.7%, the survival time increased from 3.8 to 10.1 days, the incidence of pneumonia decreased from 85.7% to 48.7%, the average intensity of pneumonia decreased from 66.4% to 9.9%, and virus titres in the lungs decreased by 3.5-4.0 lg EID50 (p less than 0.05). In the groups of mice infected with remantadine-resistant strain of influenza virus and Staphylococcus remantadine showed no significant effect on these parameters: the lethality decreased by 6.7% only, the average survival time increased only by 0.33 days, the incidence of pneumonia decreased by 9%, its intensity by 19.2%; influenza virus titres in the lung tissue did not change significantly.

Adamantane↗

Immunoglobulin E antibodies against Staphylococcus aureus cell walls in the sera of patients with hyperimmunoglobulinemia E and recurrent staphylococcal infection.

The specificity of antistaphylococcal antibodies of the IgE class in five patients with hyperimmunoglobulinemia E and recurrent staphylococcal infection has been investigated. Purified cell walls were prepared from various staphylococcal strains, and serum immunoglobulin E binding was measured by using a solid-phase radioimmunoassay. Immunoglobulin E binding occurred only with cell walls from Staphylococcus aureus strains, including walls from a teichoic acid-deficient mutant. Immunoglobulin E did not bind to cell wall preparations from the coagulase-negative species S. capitis, S. sciuri subsp. lentus, S. simulans, S. xylosus, staphylococcal strains RB-11 and Armour, and from a group A streptococcus strain CS44. Since the glycan backbone and the tetrapeptide (pentapeptide) subunit of the peptidoglycan of all staphylococcal strains tested are believed to be identical, it is suggested that IgE binding is related to either the peptidoglycan interpeptide bridge or an unknown antigenic structure within the cell wall of S. aureus. The pathophysiological significance of antistaphylococcal immunoglobulin E antibodies in the disorder studied is at present unknown. The formation of immunoglobulin E antibodies to S. aureus cell wall components may be a manifestation of an aberrant immunological response to S. aureus related to the undue susceptibility to staphylococcal infections in these patients.

Antibodies, Bacterial↗

Gentamicin in the treatment of staphylococcal infections.

The aminoglycoside antibiotic, gentamicin, was used to treat staphylococcal infections in eighty-six patients in an open multicentre trial. Most of the infections involved the skin and soft tissue and the lower respiratory tract. Staphylococcus aureus was the only organism isolated in seventy-four patients; mixed flora were found in twelve. Gentamicin was administered, intramuscularly or intravenously, for 7 to 12 days (mean, 10 days) in a mean dose of 3-27 mg/kg per day. Clinical and bacteriological assessment of results indicated a complete resolution of the infection in fifty-three patients (61-6%) and a marked, moderate, or slight improvement in an additional twenty-nine patients (33.7%). Thus, a total of eighty-two patients ((95.3%) showed cure or improvement while only four patients (4-6%) failed to do so. Staphylococci persisted in six patients. Superinfection also occurred in six patients, however, it was considered to be clinically significant in only four of them. Screening for eighth cranial nerve, renal, hepatic and haematological function, before, during, and after gentamicin treatment, revealed no adverse reactions in these patients.

Adolescent↗

Serious staphylococcal infections with strains tolerant to bactericidal antibiotics.

The clinical response in 20 cases of serious staphylococcal infection was compared with the in vitro resistance or "tolerance" of the infecting Staphylococcus to killing by antibiotics used in treatment. Cases were divided into two groups: (1) patients who initially received nonbactericidal antibiotics (ten cases), and (2) patients who initially received bactericidal antibiotics with or without nonbactericidal antibiotics. Mortality due to uncontrolled staphylococcal infection was 40% (4/10) in group 1 as compared with no mortality (1/10) in group0) in group 1 as compared with no mortality (0/10) in group 2. The duration of positive cultures after start of therapy in group 1 (mean, 6.1 days) was significantly longer than that in group 2 (mean, 1.3 days). The duration of fever after start of therapy in group 1 was not significantly different when compared with group 2.

Adult↗

Defective leukocytotaxia and recurrent staphylococcal infecion: deficiency of leukocytotaxia and abnormal granulocytes associated with increase serum IgE levels in an adult with recurrent staphylococcal infection.

A man who was suffering from recurrent staphylococcal infection had antecedent symptoms of severe pruritus. Laboratory investigations showed leukocytosis with eosinophilia, hyperimmunoglobulinemia of all fractions, but particularly of IgE, and a deficiency of cell-mediated immunity on in vivo testing. Phagocytosis and bactericidal activity of polymorphonuclear leukocytes were normal, but a cellular and serum-associated defect in leukocytotaxia was present. Ultrastructural changes were observed in polymorphonuclear leukocytes. Association of impaired leukocytotaxia and elevated levels of IgE is not uncommon. Recurrent bacterial infections in the patient described are probably related to defective chemotaxis.

Aged↗

Cefotaxime in the treatment of staphylococcal infections. Comparison of in vitro and in vivo studies.

Staphylococcus aureus strains are well-established pathogens that may cause mild to serious life-threatening disease. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, also have a pathogenic role in humans and cause infections primarily associated with prosthetic devices and indwelling catheters, whereas Staphylococcus saprophyticus usually causes urinary tract infections. Cefotaxime is a "third-generation" cephalosporin that is stable to the staphylococcal beta-lactamases. In vitro studies over the last 15 years have shown that this parenteral cephalosporin has remained highly active (MIC90 ranges of < or = 2-8 micrograms/ml) against oxacillin-susceptible staphylococci. Cefotaxime therapy of staphylococcal infections has resulted in clinical cure/improvement rates ranging from 78%-100% and bacteriologic eradication rates ranging from 85%-100% in a wide variety of infections. Contrary to contemporary dogma, this "third-generation" cephalosporin appears to be efficacious against staphylococcal infections from a review of 15 years of clinical experience.

Cefotaxime↗

Staphylococcal infection of open granulating wounds.

The significance of staphylococcal infection has been studied prospectively in 250 wounds healing by open granulation. In a series of 50 axillary skin excisions, 17 became infected with Staphylococcus aureus with consequent pain and delay in healing. The infections responded well to Fucidin ointment. Nasal carriers of the organism may be especially liable to this complication. In contrast, although S. aureus was not infrequently found in deep granulating wounds, there was no clear evidence of harm resulting in the 50 laparotomy wounds and 150 pilonidal sinus excisions studied. The susceptibility of superficial wounds to the infection is ascribed to friction from dressings. Deep granulating wounds are occasionally affected similarly when the cavity has filled.

Axilla↗

Phagocytic and chemotactic function of polymorphonuclear and mononuclear leucocytes in patients with recurrent staphylococcal infections.

From 21 patients with chronic or recurrent staphylococcal infections, phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear (PMN) and mononuclear (MN) leucocytes were evaluated. Also chemotactic responsiveness and the capacity of their sera to opsonize Staph. aureus was tested. The chemotactic, phagocytic and bactericidal capacity of PMN's and MN's from patients was significantly decreased. The mean uptake of Staph. aureus by patient PMN's and MN's was 65% and 44%, respectively, as compared to 85% and 75% observed with PMN's and MN's from 38 healthy donors. The phagocytic activity of 17/21 patients (81%) was below the normal range. A decreased chemotactic mobility and bactericidal capacity of patient leukocytes was also found and was always accompanied by a decreased rate of ingestion. Although a great variability was noted in the phagocytic capacity of leucocytes from patients tested repeatedly over periods up to 82 weeks, the mean value for phagocytosis remained below the normal range in 10/11 patients included in the follow-up study. Except for 1 patient with dysgammaglobulinemia, sera from the patients contained normal amounts of immunoglobulins and complement (CH50 and C3), and they all effectively opsonized Staph. aureus. The results indicate that defects in leucocyte function may be frequently involved in the pathogenesis of recurrent Staph. aureus infections.

Adolescent↗

Prophylactic effects of gamma-aminobutyrylhistidine (homocarnosine) on experimental staphylococcal infections in mice.

Prophylactic administration of the dipeptide homocarnosine induced a high degree of resistance to staphylococcal infections in Swiss albino mice. It expressed its antistaphylococcal properties 1 hr after administration, and this protection lasted for at least 1 month. Although 5 mg per animal (approximately 200 to 250 mg/kg) was routinely used in our studies, experiments showed that comparable results could be obtained with 1.5 mg per animal. Rechallenge experiments indicated that an active infection by itself may confer immunity up to 4 weeks, but an infection after treatment with homocarnosine gave complete immunity to reinfection for at least 2 months. Studies in vitro showed that homocarnosine had no effect on the growth or certain other characteristics (ability to ferment mannitol, liquefy gelatin, and to produce coagulase, deoxyribonuclease, and pigment) of S. aureus. It appears that resistance induced by this peptide is an indirect effect mediated by some nonimmunological host reaction. The possible involvement of homocarnosine, among other compounds, in the protective action of deproteinized beef extract against staphylococcal infections is suggested.

Animals↗