title: Oritavancin - a new semisynthetic lipoglycopeptide agent to tackle the challenge of resistant gram positive pathogens.
abstract: Natural glycopeptide antibiotics like vancomycin and teicoplanin have played a significant role in countering the threat posed by Gram-positive bacterial infections. 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 and the current development of antibiotics falls short of meeting the needs. Oritavancin (LY-333328 diphosphate), a promising novel second-generation semisynthetic lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has concentration-dependent activity against a variety of Gram-positive organisms specially methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant Staphylococcus aureus (VISA), Streptococcus pneumoniae and vancomycin-resistant enterococcus. It is rapidly bactericidal against many species and in particular for enterococci where vancomycin and teicoplanin are only bacteriostatic even against susceptible strains. The pharmacokinetic profile of oritavancin has not been fully described; however, oritavancin has a long half-life of about 195.4 hours and is slowly eliminated by renal means. Oritavancin is not metabolized by the liver in animals. Oritavancin will most probably be prescribed as a once-daily dose and it demonstrates concentration-dependent bactericidal activity. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and II clinical trials. In a Phase III clinical trial, oritavancin has achieved the primary efficacy end point in the treatment of complicated Gram-positive skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being administration site complaints, headache, rhinitis, dry skin, pain, increases in liver transaminases and accumulation of free cholesterol and phospholipids in phagocytic (macrophages) and nonphagocytic (fibroblast) cells. Oritavancin appears to be a promising antimicrobial alternative to vancomycin (with additional activity against Staphylococcus and Enterococcus resistant to vancomycin) for the treatment of complicated Gram-positive skin and skin-structure infections. Additional clinical data are required to fully explore its use.
authors.affiliation: Department of Pharmacology, Division of Pathology, School of Medicine, International Medical University (IMU), No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
authors.forename: Biswadeep
authors.initials: B
authors.lastname: Das
authors.forename: Chayna
authors.initials: C
authors.lastname: Sarkar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schachter
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D000077427:Lipoglycopeptides; D016896:Treatment Outcome; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin