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[Chemotherapeutic effectiveness of a new derivative of 5-alkyl-3N-furanones in experimental staphylococcal infection].

High chemotherapeutic efficacy of the compound 1929, a new derivative of 5-alkyl-3H-furanones was shown in albino mice with experimental staphylococcal infection caused by intraperitoneal administration to the animals. The efficacy was found to be higher than that of furagin used for comparison. The average therapeutic dose (AD50) of the compound for intraperitoneal administration amounted to 40 mg/kg while the average lethal dose (LD50) was 3000 mg/kg.

Administration, Oral↗

[The antibacterial effects of homologous interferons in an experimental staphylococcal infection].

Homologous interferons (IF) of the 1st and 2nd types are studied for their effect on the course of experimental staphylococcal infection. A model of intracutaneous infection of animals is used. Survival of mice, dynamics of the agent elimination from the organism, functional activity of phagocytes in dynamics of the infectious process during IF administration are studied. Only preparations of natural IF are found to possess a protective effect. The recombinant gamma-IF does not prevents from the mouse death and exerts no effect on the dynamics of elimination of agents from the organism.

Animals↗

Therapy of staphylococcal infections with cefamandole or vancomycin alone or with a combination of cefamandole and tobramycin.

Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.

Anti-Bacterial Agents↗

Pharmacokinetics of enrofloxacin in clinically normal dogs and mice and drug pharmacodynamics in neutropenic mice with Escherichia coli and staphylococcal infections.

Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 10(6) colony-forming units of E coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log10 colony-forming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way ANOVA was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E coli and staphylococci is concentration dependent and not time dependent.

Animals↗

Antibodies to cell wall peptidoglycan of Staphylococcus aureus in patients with serious staphylococcal infections.

An enzyme-linked immunoassay was used to detect antibodies to the cell wall peptidoglycan of Staphylococcus aureus in human sera. All 170 sera from donors and patients with staphylococcal and nonstaphylococcal infections contained IgG antibodies to peptidoglycan; antibody levels varied with age, and transplacental transfer occurred. IgM antibodies to peptidoglycan were not found in donors and were present in only one patient with serious staphylococcal infection. Significantly elevated levels of IgG antibodies to peptidoglycan were observed in 20 (80%) of 25 patients with deep tissue infection with S. aureus but in only two (9%) of 22 patients with superficial staphylococcal infection. An increase in levels of antibodies to peptidoglycan generally coincided with an increase in level of IgG antibodies to teichoic acid. No cross-reactivity between peptidoglycan and teichoic acid was observed. Thus, staphylococcal peptidoglycan is immunogenic in humans, and testing for IgG antibodies to peptidoglycan may be useful in the diagnosis and follow-up of serious staphylococcal infections.

Antibodies, Bacterial↗

[Activity of myocardial, kidney and serum isoenzymes in experimental staphylococcal infection].

Alteration in activity and spectrum of multiple forms of some enzymes were studied in rat blood serum, myocardium and kidney cells in dynamics of staphylococcal infection as well as after administration of exo- and intracellular protein of staphylococci into animals. In the infection intracellular distribution of enzymes was impared in animal tissues studied and "tissue" isoforms of enzymes were accumulated in blood. Staphylococcal exo- and intracellular substances were found to effect dissimilarly on spectrum and activity of isoenzymes from rat kydney, myocardium and blood serum.

Acid Phosphatase↗

Nafcillin concentration in cerebrospinal fluid during treatment of staphylococcal infections.

The nafcillin concentration of simultaneous cerebrospinal fluid (CSF) and serum specimens from nine patients being treated with parenteral nafcillin for staphylococcal infection were measured. Marked variations in the ratio of CSF/serum nafcillin concentration were observed. However, the concentration of nafcillin in the CSF was greater than the minimum lethal concentration (MLC) for Staphylococcus aureus in eight of the nine patients. In five patients with CSF pleocytosis, the nafcillin concentration was three to 100 times the MLC. These results support the recommendation to use nafcillin in doses of at least 100 to 200 mg/kg body weight-day for treatment of meningitis caused by S. aureus.

Adolescent↗