Transduction of drug-resistances in Staphylococcus. II. Transduction of chloramphenicol-resistance in both Staphylococcus aureus and Staphylococcus epidermidis by typing phage 80.
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A total of 20 different allergens extracted from various staphylococcal strains were studied in the delayed hypersensitivity reactions in experiments on guinea-pigs. The most intensive dermatoallergic reactions were observed after the injection of the cytoplasmic fraction, acidic and alkaline extracts; reactions to the allergen of Ando-Verzhikovsky were less pronounced. The cytoplasmic fraction and the allergen of ando-Verzhikovsky were more active in the reaction of leukocyte migration inhibition in the blood. Both common and individual allergenic components were detected. No correlation between the results of the immunochemical and allergological studies of staphylococcal extracts was revealed.
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OBJECTIVE: To determine if head-injured patients with premorbid nasal colonization with Staphylococcus aureus are at increased risk for S. aureus infection. DESIGN: Patients admitted over a 2-yr period were enrolled if they met the following criteria: Injury Severity Score > or = 9, intensive care unit (ICU) admission, hospitalization in another hospital < 24 hrs, no recent use of antibiotics. SETTING: Acute care trauma facility. PATIENTS: Any patient sustaining acute, blunt, or penetrating injury and meeting the enrollement criteria were eligible. INTERVENTIONS: Swab cultures of both internal nares were performed within 72 hrs of readmission and cultured for S. Aureus. Patients were prospectively monitored for S. Aureus infections until discharge. MEASUREMENTS AND MAIN RESULTS: Admission nasal cultures were positive (NC+) for S. aureus in 144 of the 776 patients cultured. Forty of the 144 NC+ patients had isolated head (37) or high cervical spine (3) injury, and 11 of that group (27.5%) developed S. aureus infections. The remaining 104 patients positive for S. aureus on admission had no head injury (74) or head combined with torso and extremity injuries (30). S. aureus infection was diagnosed in 11 of the 104 patients (10.6%). The difference in incidence of infections is significant (p <.01), as is the difference in incidence of pneumonia (20% vs. 3.8%, respectively [p <.01]). Organisms causing pneumonia were often the same organisms isolated from the nares on admission. CONCLUSIONS: Nasal colonization with S. aureus at the time of severe head injury increases the risk of S. aureus pneumonia during hospitalization. Prophylactic measures against S. aureus pneumonia may help reduce the length and cost of hospitalization.
Staphylococci grow and cause infection under the iron-restricted conditions found in vivo. They therefore must possess mechanisms to obtain iron for metabolism from this environment. To determine if staphylococci can extract iron bound to human transferrin, we labelled transferrin with 55Fe and performed uptake assays on cells grown in iron-restricted and iron-plentiful conditions. Growing cultures of Staphylococcus aureus NCTC 8532 could take up radioactive iron during mid- to late-exponential phase of growth. This process was iron-regulated and did not require direct contact between the cell and the labelled transferrin. Siderophore production was detected during this phase, but reductase or protease activity was not. S. epidermidis ATCC 14990 could not access 55Fe bound to transferrin, nor did this isolate produce siderophore, reductase or protease. This difference in the ability to acquire iron bound to transferrin may contribute to the increased virulence of S. aureus when compared to S. epidermidis.
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Although the definition of S. aureus nasal carriage in peritoneal dialysis patients is variable, carriage is often defined as 2 or more positive cultures for S. aureus. We investigated the relationship between S. aureus infections and nasal carriage (defined as 1 or more positive nose cultures) in 138 patients on peritoneal dialysis. By this definition, approximately 50% of the patients were carriers. The rates of S. aureus exit-site infection (0.28/year vs 0.43/year, p < 0.001) and peritonitis (0.08/year vs 0.20/year, p < 0.001) were lower in the noncarriers (patients with no positive nose cultures) than in those patients who had 1 or more positive nose cultures. Patients with only 1 positive nose culture had a similar S. aureus exit-site infection rate (0.31/year vs 0.28/year), but a higher peritonitis rate (0.24/year vs 0.08/year, p < 0.001) compared to those patients with no positive nose cultures. However, patients with 2 or more positive nose cultures were at increased risk for both S. aureus exit-site infections and peritonitis. This relationship held even when only patients with frequent nose cultures were included in the analysis. Thus patients with even 1 positive nose culture for S. aureus are at risk for S. aureus peritonitis and should not be classified as noncarriers.
The penicillin-binding proteins of a total of 25 staphylococcal strains belonging to five different species were analyzed. All strains of the same species showed an identical penicillin-binding protein pattern which clearly differed from that of strains of the other species. Staphylococcus aureus, Staphylococcus intermedius, Staphylococcus simulans, and the dolphin strains were found to contain two to four penicillin-binding proteins. Strains of Staphylococcus hyicus exhibited only one penicillin-binding protein.
Staphylococcus aureus and Staphylococcus epidermidis are organisms that frequently cause conjunctivitis or blepharoconjunctivitis. We describe a patient with methicillin-resistant S. aureus and S. epidermidis conjunctivitis who was treated successfully using an extemporaneously prepared topical ophthalmic solution of vancomycin hydrochloride 31 mg/mL. Studies describing the preparation, stability, and comfort of this solution, as well as reports pertaining to efficacy, are reviewed. Controlled clinical trials evaluating the safety and efficacy of vancomycin ophthalmic solution have not yet been performed.
A close homologue of the mec A gene, the primary drug resistance determinant in methicillin resistant Staphylococcus aureus (MRSA), is ubiquitous in the animal commensal species Staphylococcus sciuri, yet most isolates of this staphylococcal species are susceptible to beta-lactam antibiotics including methicillin. Recently, we showed that in a methicillin-resistant mutant of S. sciuri prepared in the laboratory, the mec A homologue is converted to an antibiotic resistance gene by a point mutation introduced into the -10 consensus of the promoter and such promoter-up mutants of the S. sciuri mec A can express a significant degree of methicillin resistance when introduced into an antibiotic-susceptible strain of S. aureus. We now demonstrate that in this system further increase of the drug resistance phenotype may be achieved under antibiotic pressure by at least two different mechanisms. The first one of these involves the introduction of a point mutation at nucleotide Nt 1889 in the coding region of the S. sciuri-derived mec A determinant, resulting in the replacement of an asparagine with a threonine residue downstream of the conserved SXXK motif which causes extensive reduction in the beta-lactam antibiotic binding capacity (affinity) of the penicillin binding protein (PBP) encoded by the S. sciuri mec A homologue. A second, distinct, mechanism causing increased methicillin resistance is associated with mutation(s) of unknown nature in the genetic background of the S. aureus host.
Checks were applied to 3,213 dead or ill broiler chickens and broiler parents for the purpose of elucidating enzootic or epizootic Staphylococcus aureus infections which had occurred on three industrialised poultry units. Rates of Staphylococcus aureus detection and identification declined by the following order: staphylococcal septicaemia (100 per cent), dermatitis (75.42 per cent), arthritis and tenosynovitis or osteomyelitis (64.59 per cent), wound infections (24.02 per cent), infection of bursa suprasternalis (18.94 per cent), underdevelopment (8.70 per cent), navel-yolksac-peritonitis (7.83 per cent), and conjunctivitis (7.14 per cent). Staphylococcus aureus was found to be the most important pathogen of arthritis with synovitis and of osteomyelitis with epiphysiolysis, the rate of detection being directly correlated with the severity of the pathologico-anatomic alterations established. Attempts to culture mycoplasmas from irritated synovial sheaths were successful only in three of 56 examined animals (5.3 per cent). The site variety of gallinae or strains of the crystal-violet Type A with lysis patterns of 84, 53, 77 and 84 accounted for 78.1 per cent of all Staphylococcus aureus strains isolated from infected fowl. Their percentual importance was 85.0 for septicaemia, dermatitis, and arthritis with synovitis and osteomyelitis. For prophylaxis and control of Staphylococcus aureus infections of fowl on elimination of predisposing factors and on the control of epidemic occurrence of the above types.
Staphylococcus aureus is a major human pathogen. Pathogenic effects are largely due to production of bacterial toxins, whose synthesis is controlled by an mRNA molecule termed RNAIII. The S. aureus protein called RAP (RNAIII-activating protein) is secreted and activates RNAIII production by inducing the phosphorylation of its target protein TRAP (target of RAP). Antibodies to TRAP have been shown to suppress exotoxin production by S. aureus in vitro, suggesting that TRAP may be a useful vaccine target site. Here we showed that a peptide TA21 was identified by screening a phage display library using anti-TRAP antibodies. Mice vaccinated with Escherichia coli engineered to express TA21 on their surface (FTA21) were protected from S. aureus infections, using sepsis and cellulitis mice models. By sequence analysis, it was found that the TA21 is highly homologous to the C-terminal sequence of TRAP which is conserved among S. aureus and Staphylococcus epidermidis, suggesting that peptide TA21 may be a useful broad vaccine to protect from infection caused by various staphylococcal strains.
Bovine mastitis caused by Staphylococcus aureus is responsible for major economic losses to the dairy industry, and more-effective therapeutic or preventive approaches are sorely needed. The predominance of staphylococcal capsular polysaccharide types 5 and 8 among human isolates from many sources is well documented, but there seems to be a greater variation in the distribution of capsular serotypes among isolates from cows. A total of 636 isolates of S. aureus from cases of bovine mastitis in Sweden, Denmark, Finland, Iceland, Ireland, and the United States were investigated for production of capsular polysaccharide types 5 and 8. Approximately half of all the European isolates tested were of serotype 8, although variation among countries and among isolates of clinical and subclinical origin was observed. Sweden had the highest frequency (87%) of serotypeable isolates, and Finland had the lowest (48%). Capsule types 5 and 8 accounted for only 42% of the U.S. isolates tested. A few isolates showed weak reactivity with CP5 antiserum in a colony blot assay, and an enzyme-linked immunosorbent assay inhibition method confirmed that the levels of capsule produced by these strains were <10% of those produced by control strains. Fifty isolates that failed to react with capsular antisera all possessed the genes for production of capsular polysaccharide type 5 or 8. These results underscore the variability in capsule production by bovine isolates of S. aureus from different geographic regions. This information is important for the rational design of a capsule-based vaccine to prevent S. aureus bovine mastitis.
Bactericidal activities of LY191145, an investigational glycopeptide, and vancomycin against Staphylococcus aureus were evaluated. Only LY191145 at a concentration 16-fold greater than the MIC was able to achieve 99.9% killing against methicillin-susceptible S. aureus (ATCC 25923; 8.0 h). Both agents demonstrated 99.9% killing against methicillin-resistant clinical isolate S. aureus MRSA67 over 24 h at concentrations 4-, 8-, and 16-fold greater than the MIC, but bacteria were killed at a more rapid rate by LY191145 (1.63 versus 5.02 h; P < 0.001). Against strain ATCC 25923- and MRSA67-infected fibrin clots, total reductions by LY191145 and vancomycin over 72 h were not statistically significantly different at a concentration 16 times the MIC (1.12 +/- 0.31 and 1.23 +/- 0.13 and 1.40 +/- 0.17 and 1.36 +/- 0.37 CFU/g; respectively). Increasing the drug concentration to 50 times the MIC did not alter the values significantly, and there was no statistically significant difference between the two agents. Overall, LY191145 exhibited more rapid bactericidal activity than vancomycin against S. aureus, and a concentration 16-fold greater than the MIC appears to be optimal.
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The efficiency of vancomycin hydrochloride in the treatment of septicemia due to polyresistant aureus staphylococcus is illustrated by the observation of a patient affected with a necrotic and hemorrhagic acute pancreatitis and post-operative septicemic syndrome, which has been cured after a one-month treatment with a daily dose of two grammes. The vancomycin hydrochloride, because of its potential toxicity on the kidneys and cochlea should be reserved to the treatment of major staphylococcic infections. It could be prescribed either alone or in association, with a mean daily dose of 30 milligrammes a kilo, slowly administered by intravenous way. The side effects are prevented by adjusting the doses in case of renal insufficiency and by controlling the serous concentrations in case of a long continued treatment.