Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most complicated skin and skin structure infections (cSSSI) are caused by Staphylococcus aurens (SA) and streptococcus (SC). More and more isolates of SA and SC are resistant to methicillin (MRSA) and there are concerns that SA will become resistant to vancomycin (VRSA), the current standard of treatment. Dalbavancin (BI397) is a novel semisynthetic lipoglycopeptide that was designed to improve uon the natural glycopeptides currently available, vancomycin and teicoplanin. Phase-III clinical trials comprising more than 1,500 patients evaluating once-weekly dalbavancin in skin and soft tissue infections (SSTIs) associated with Gram-positive bacteria met the primary endpoint of non-inferiority in patients whose clinical response was evaluated at 2 weeks following therapy when compared to linezolid, cefazolin, or vancomycin, the three most widely administered standard-of-care agents for SSTIs. The side effect profile of dalbavancin is mild, with headache and pyrexia being the most adverse effects. Once-a-week dosing with dalbavancin may obviate the need for the continued presence of IV lines in some patients, which could translate into fewer local infections and blood stream infections and which could facilitate transfer of the patients to skilled nursing facilities. Unlike other new antibiotics, such as oritavancin and tigecycline, dalbavancin is not active against vancomycin-resistant enterococcus or VRSA. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred other newer agents such as linezolid.
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PMID:Dalbavancin: a review for dermatologists. 1708 61

Dalbavancin is a second-generation lipoglycopeptide bactericidal agent. Due to its once-weekly intravenous (i.v.) dosing and greater tissue penetration, dalbavancin may offer advantages in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) as compared to vancomycin, the gold standard in the treatment of MRSA. Dalbavancin binds to the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors in bacterial cell walls. Such binding blocks enzymes involved in the final stages of peptidoglycan synthesis and cell wall formation. Dalbavancin exhibits an elimination half-life of approximately 200 hours, allowing it to be dosed weekly. The best-studied dosing schedule for dalbavancin involves the i.v. administration of 1 g of dalbavancin followed by 500 mg one week later. Phase III clinical trials comprising more than 1,500 patients evaluated once-weekly dalbavancin in Gram-positive skin and soft tissue infections (SSTIs). When compared to linezolid, cefazolin or vancomycin, dalbavancin met the primary endpoint of noninferiority at two weeks following therapy. The side-effect profile of dalbavancin is mild, with headache and pyrexia being the most common adverse effects. Dalbavancin is eliminated renally and hepatically, and does not need dose adjustments in patients with renal insufficiency. Once-weekly dosing with dalbavancin gives it another advantage when compared with vancomycin, and may alleviate the need for the continued presence of indwelling catheters in some patients with SSTIs and other infections requiring prolonged doses of antibiotics. While some in vitro evidence supports dalbavancin's effectiveness against vancomycin-resistant S. aureus, the preponderance of in vivo evidence does not demonstrate its effectiveness against vancomycin-resistant S. aureus.
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PMID:Dalbavancin: a review. 1772 97

Glycopeptide antibiotics represent an important class of microbial compounds produced by several genera of actinomycetes. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among gram-positive organisms has been increasing steadily during the past several decades. Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of Gram-positive organisms specially multidrug resistant Staphylococcus aureus, but no activity against Gram-negative or vancomycin-resistant enterococci that possess vanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well-tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being pyrexia, headache, diarrhea. Dalbavancin appears to be a promising antimicrobial agent for the treatment of Gram-positive infections. Additional clinical data are required to fully assess its use. Despite the remarkable and favorable pharmacokinetic and pharmacodynamic properties, the use of this potent agent should be restricted to severe infections due to multidrug resistant organisms to limit the risk of selection of resistance. It is active against Gram-positive aerobes and anerobes, including resistant pathogens, with the exception of strains producing vanA-mediated resistance. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred over other newer agents such as linezolid in the next decade remains to be seen.
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PMID:Review: dalbavancin--a novel lipoglycopeptide antimicrobial for gram positive pathogens. 1816 24