Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bloodstream infections, especially those arising from multidrug-resistant strains, are an alarming public health threat requiring continuous efforts for new drug development. In this review, antibiotics at an advanced development stage for the treatment of patients with bloodstream infections are identified through a search of the available literature sources. Eight compounds currently undergoing phase II and/or phase III trials were identified. Isavuconazole, a triazole, is undergoing a phase III trial for the potential treatment of candidemia. Ceftobiprol medocaril, which belongs to the cephalosporin class, is undergoing regulatory review for the treatment of skin infections. Three lipoglycopeptides, oritavancin, dalbavancin and telavancin, are being tested against Gram-positive cocci in clinical trials. Also, human lactoferrin peptide 1-11, which appears to be a promising agent, is being tested in patients with Staphylococcus epidermidis bacteremia and in patients with candidemia. Iclaprim, a novel dihydrofolate reductase inhibitor, has completed two phase III trials for complicated skin and skin structure infections. The revival of an old class of antibiotics, polymyxins, in an effort to combat resistance, has also necessitated further investigation of these agents; colistin (polymyxin E) is at the forefront of this class of compounds, and is being assessed in a phase III efficacy trial. This overview of investigational antibiotics for bloodstream infections highlights that the pace of antimicrobial drug research and development is slower than the evolution of resistance. Only eight relevant compounds were identified in the pipeline of antibiotic research, none of which demonstrate a novel mechanism of action.
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PMID:Investigational antimicrobial drugs for bloodstream infections. 1866 35

Antibiotic resistance is an ever-increasing concern in the treatment of severe skin and skin-structure infections, pneumonia, bacteremia and other serious infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus, group A Streptococcus and vancomycin-resistant Enterococcus. In this review, we summarize the current status of both US FDA-approved and investigational agents aimed at this group of pathogens. We also describe, in detail, the chemistry, mechanism of action, pharmacokinetic properties and spectrum of microbiological activity of iclaprim, a novel dihydrofolate reductase inhibitor recently awarded fast-track approval status by the FDA. Finally, we review the clinical efficacy of iclaprim compared with linezolid for skin and skin-structure infections as demonstrated in Phase III randomized, controlled trials, and comment on its potential role in the treatment of other severe infections with drug-resistant Gram-positive pathogens.
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PMID:Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections. 1925 39