title: Early appropriate therapy of Gram-positive bloodstream infections: the conservative use of new drugs.
abstract: Among the Gram-positive organisms, meticillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium represent the biggest therapeutic hurdles. The evolution of MRSA exemplifies the genetic adaptation of an organism into a first-class multidrug-resistant pathogen. Glycopeptides such as vancomycin have been the treatment of choice for MRSA, but poor outcomes have frequently been reported, particularly among isolates with higher minimum inhibitory concentrations (MICs) within the susceptible range (< or =2 mg/L). Further more, vancomycin's limitations as an antibacterial agent include slow bactericidal activity and relatively poor tissue penetration. Inadequate dosing may, however, contribute to vancomycin's poor performance; the standard recommendation for trough concentrations of 5-10 mg/L is inadequate for serious infections such as bacteraemia and endocarditis. Trough levels of 15-20 mg/L are probably necessary; however they are often associated with increased nephrotoxicity. Despite the recent dramatic reduction in antibiotic research by pharmaceutical companies, a few compounds have been developed to treat Gram-positive infections. Quinupristin-dalfopristin, although shown to have in vitro activity against MRSA, is not approved by the US Food and Drug Administration for the treatment of MRSA, and cannot be recommended for the treatment of S. aureus bacteraemia, except under exceptional circumstances. Although linezolid and tigecycline may be useful in specific situations, they cannot be routinely recommended for the treatment of MRSA bacteraemia because of safety concerns and very limited available clinical data. Daptomycin has recently been proven to be effective and well tolerated for meticillin-sensitive S. aureus and MRSA bacteraemia, including right-sided endocarditis.
authors.affiliation: Infectious Diseases Department, University of Insubria, Viale Borri 57, 21100 Varese, Italy. paolo.grossi@uninsubria.it
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Grossi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D016984:Enterococcus faecium / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents