salicylates and Staphylococcal-Infections

Clinicians administering potent therapeutic agents must be aware of their side-effects. The gut is an important site of adverse drug reactions and drug-induced disease must always be considered in the differential diagnosis of patients presenting with gastrointestinal symptoms. A careful drug history must therefore be taken in all such patients. Symptoms can often be related to drug ingestion, but late effects also occur. The presence of blood in vomitus or stool is pathognomonic of serious pathology which may be drug-induced and requires further investigation. Upper gastrointestinal haemorrhage and pseudomembranous colitis are potentially fatal manifestations of drug therapy. Gastrointestinal symptoms can often be avoided if therapy is taken with meals or in a smaller dose, but drug withdrawal is always the first line of management in patients whose symptoms may be drug-induced.

Topics: Adrenal Cortex Hormones; Cathartics; Colon; Constipation; Diarrhea; Enterocolitis, Pseudomembranous; Esophagus; Gastrointestinal Diseases; Humans; Indomethacin; Intestine, Small; Mouth Mucosa; Phenylbutazone; Propionates; Prostaglandins; Salicylates; Staphylococcal Infections; Stomach; Stomatitis; Tongue

The Staphylococcus aureus can switch to a transient genotype-invariant dormancy, known as a persister, to survive treatment with high doses of antibiotics. This transient persister is an important reason underlying its resistance. There is an urgent need to find new antibacterial agents capable of eradicating methicillin-resistant S. aureus (MRSA) persisters. In this study, 37 new derivatives of cajaninstilbene acid (CSA) were designed and synthesized, and their biological activity against MRSA persisters was evaluated. Most of the newly synthesized derivatives exhibit more potent antimicrobial properties against S. aureus and MRSA than CSA itself, and 23 of the 37 derivatives show a tendency to eradicate MRSA persisters. A representative compound (A6) was demonstrated to target bacterial cell membranes. It eradicated the adherent biofilm of MRSA in a concentration dependent manner, and showed a synergistic antibacterial effect with piperacilin. In a model mouse abscess caused by MRSA persisters, A6 effectively reduced the bacterial load in vivo. These results indicate that A6 is a potential candidate for treatment of MRSA persister infections.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Cell Survival; Cell Wall; Disease Models, Animal; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; RAW 264.7 Cells; Salicylates; Skin Diseases; Staphylococcal Infections; Staphylococcus aureus; Stilbenes; Structure-Activity Relationship

The purpose of these experiments was to (1) assess differences in mastitis pathogen strain sensitivities to teat disinfectants (teat dips), and (2) determine the optimum time for premilking teat dips to remain in contact with teat skin to reduce pathogen loads on teat skin. Two experiments were conducted using the excised teat model. In experiment 1, the differences in mastitis pathogen strain sensitivities to 4 commercially available dips (dip A: 1% H2O2; dip B: 1% chlorine dioxide; dip C: 1% iodophor; and dip D: 0.5% iodophor) were evaluated. Four strains of 11 common mastitis pathogens (Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis, Streptococcus dysgalactiae, Streptococcus uberis, Escherichia coli, Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus hyicus, Staphylococcus xylosus, and Staphylococcus haemolyticus) were tested. In experiment 2, the percentage log reduction of mastitis pathogens (Escherichia coli, Streptococcus uberis, Streptococcus dysgalactiae, Klebsiella species, Staphylococcus chromogenes, Staphylococcus haemolyticus, Staphylococcus xylosus, and Staphylococcus epidermidis) on teat skin with 3 commercially available teat dips: dip A; dip D; and dip E: 0.25% iodophor, using dip contact times of 15, 30, and 45 s, was evaluated. Experiment 1 results indicated significant differences in strain sensitivities to dips within pathogen species: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Species differences were also found where Mycoplasma bovis (97.9% log reduction) was the most sensitive to tested teat dips and Staphylococcus haemolyticus (71.4% log reduction) the most resistant. Experiment 2 results indicated that contact times of 30 and 45 s were equally effective in reducing recovered bacteria for dips D and E and were also significantly more effective than a 15-s contact time. No differences were seen in recovered bacteria between tested contact times after treatment with dip A. It can be concluded that different mastitis pathogen species and strains within species may possess different sensitivities to teat dips, which may have implications in selection of teat dips on dairies. Furthermore, a 30-s premilking dip contact time for iodophors and 15 s for H2O2 dips may be optimal in reducing pathogen load in the shortest amount of time. A reduction in premilking teat dip contact time may improve milking parlor efficiency.

Topics: Animals; Anti-Infective Agents, Local; Bacterial Load; Cattle; Chlorine Compounds; Escherichia coli; Female; Hydrogen Peroxide; Mammary Glands, Animal; Mastitis, Bovine; Oxides; Salicylates; Skin; Species Specificity; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Streptococcus agalactiae; Time Factors

Increasing antibiotic resistance in human pathogens necessitates the development of new approaches against infections. Targeting virulence regulation at the transcriptional level represents a promising strategy yet to be explored. A global transcriptional regulator, MgrA in Staphylococcus aureus, was identified previously as a key virulence determinant. We have performed a fluorescence anisotropy (FA)-based high-throughput screen that identified 5, 5-methylenedisalicylic acid (MDSA), which blocks the DNA binding of MgrA. MDSA represses the expression of α-toxin that is up-regulated by MgrA and activates the transcription of protein A, a gene down-regulated by MgrA. MDSA alters bacterial antibiotic susceptibilities via an MgrA-dependent pathway. A mouse model of infection indicated that MDSA could attenuate S. aureus virulence. This work is a rare demonstration of utilizing small molecules to block protein-DNA interaction, thus tuning important biological regulation at the transcriptional level.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Mice; Mice, Inbred BALB C; Models, Molecular; Salicylates; Staphylococcal Infections; Staphylococcal Protein A; Staphylococcus aureus; Transcription Factors; Transcriptional Activation; Virulence; Virulence Factors

Osteomyelitis was induced in the tibiae of rabbits by injecting a suspension of Staphylococcus aureus and sodium tetradecylsulphate, a sclerosing agent. These rabbits were then divided into two groups: one group remained untreated and the other was fed a diet containing sodium salicylate. Two and four weeks after induction of osteomyelitis the tibiae taken from untreated rabbits with osteomyelitis and incubated in vitro released significantly more prostaglandin E and F than the control uninjected or uninfected tibiae. Tibiae taken from rabbits treated with sodium salicylate showed minimal radiographic changes and a significantly decreased release of prostaglandin E and F compared to the untreated rabbits. Prostaglandins are known to be potent bone resorbing agents and the results of this study suggest that they may also be involved in the destruction of bone which is characteristic of osteomyelitis. The treatment of rabbits with osteomyelitis using anti-inflammatory drugs, which block synthesis of prostaglandins, in addition to antibiotics, may prevent the destruction of bone and possible sequestration thereby decreasing the risk of chronic disease.

Topics: Animals; Bone Resorption; Osteomyelitis; Prostaglandins E; Prostaglandins F; Rabbits; Radiography; Salicylates; Staphylococcal Infections; Tibia

Topics: Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents; Edema; Hydrocortisone; Male; Rats; Salicylates; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Autoantibodies; Chloramphenicol; Chronic Disease; Eczema; Humans; Immunotherapy; Ointments; Oxytetracycline; Penicillin Resistance; Penicillins; Salicylates; Skin Diseases, Infectious; Staphylococcal Infections; Streptomycin; Tars; Zinc

Topics: Bee Venoms; Humans; Salicylates; Staphylococcal Infections; Staphylococcus

Topics: Bacteria; Salicylates; Staphylococcal Infections; Staphylococcus; Vitamin B Complex; Vitamins