Limits...
Update on the appropriate use of linezolid in clinical practice.

Manfredi R - Ther Clin Risk Manag (2006)

Bottom Line: During the recent years, the phenomenon of multiresistant Gram-positive cocci is spreading to the community, where the retrieval of such microorganism is progressively increasing.The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains.The first oxazolidinone derivative linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin, and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds on the pipeline, represent an effective response to the great majority of these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, Division of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital Bologna, Italy.

ABSTRACT
Multi-antibiotic resistant Gram-positive cocci, which include Staphylococcus aureus, the coagulase-negative staphylococcal group, Enterococcus faecalis and Enterococcus faecium, and other streptococci, represent emerging pathogens especially in the setting of the immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are of concern, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics or immunosuppressive drugs are widely administered. During the recent years, the phenomenon of multiresistant Gram-positive cocci is spreading to the community, where the retrieval of such microorganism is progressively increasing. The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains. The first oxazolidinone derivative linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin, and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds on the pipeline, represent an effective response to the great majority of these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern. The main problems related to the epidemiological and clinical features of multiresistant Gram-positive infection, the potential clinical indications of all recently available compounds compared with the standard of care of treatment of resistant Gram-positive infections, and updated data on efficacy and tolerability of linezolid as the golden standard compound for vancomycin-resistant Gram-positive cocci in multiple clinical situations, are outlined and updated on the ground of an extensive review of all the available, recent evidences coming from the international literature.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of linezolid, the first oxazolidinone antimicrobial compound.The first ring (from the left) contains a morpholino group, which enhances its pharmacokinetic profile and improves water solubility. In the second ring (from the left), the strategically located fluorine atom enhances drug activity.The “bridge” structure after the third ring (from the left) bears a necessary 5-(S) configuration.The terminal (right) C-5 acylaminomethyl group is essential for ensuring the unique drug characteristics.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1936365&req=5

fig1: Chemical structure of linezolid, the first oxazolidinone antimicrobial compound.The first ring (from the left) contains a morpholino group, which enhances its pharmacokinetic profile and improves water solubility. In the second ring (from the left), the strategically located fluorine atom enhances drug activity.The “bridge” structure after the third ring (from the left) bears a necessary 5-(S) configuration.The terminal (right) C-5 acylaminomethyl group is essential for ensuring the unique drug characteristics.

Mentions: Linezolid represent the first member of a novel class of oxazolidinone derivatives (a, q), which encompasses an effective activity spectrum which covers all the most important Gram-positive organisms, including those resistant to methicillin and glycopeptides. The chemical structure of linezolid is sketched in Figure 1. The oxazolidinones have an unique mode of action, which inhibits the initiation of the synthesis of bacterial proteins and enzymes, by preventing the formation of the ternary complex at 70S ribosomal subunit (Stevens et al 2004), by an apparent double blockade of both the 50S and the 30S bacterial ribosomal subunits. The uniquely particular mechanisms of action of linezolid, which includes a blockade of ribosomal assemblation which occurs before the initiation of bacterial protein synthesis (Stevens et al 2004), makes very improbable the emerging of cross resistance with other antimicrobial compounds. Single episodes of linezolid resistance have until now been anecdotally reported, especially after long-term and low-dosage courses, although it appears to be extremely rare among Staphylococci (Herrero et al 2002; Meka and Gold 2004), while linezolid-resistant Enterococci have been occasionally reported in intensive care units (Weigelt et al 2005), reports for both are now increasingly common.


Update on the appropriate use of linezolid in clinical practice.

Manfredi R - Ther Clin Risk Manag (2006)

Chemical structure of linezolid, the first oxazolidinone antimicrobial compound.The first ring (from the left) contains a morpholino group, which enhances its pharmacokinetic profile and improves water solubility. In the second ring (from the left), the strategically located fluorine atom enhances drug activity.The “bridge” structure after the third ring (from the left) bears a necessary 5-(S) configuration.The terminal (right) C-5 acylaminomethyl group is essential for ensuring the unique drug characteristics.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1936365&req=5

fig1: Chemical structure of linezolid, the first oxazolidinone antimicrobial compound.The first ring (from the left) contains a morpholino group, which enhances its pharmacokinetic profile and improves water solubility. In the second ring (from the left), the strategically located fluorine atom enhances drug activity.The “bridge” structure after the third ring (from the left) bears a necessary 5-(S) configuration.The terminal (right) C-5 acylaminomethyl group is essential for ensuring the unique drug characteristics.
Mentions: Linezolid represent the first member of a novel class of oxazolidinone derivatives (a, q), which encompasses an effective activity spectrum which covers all the most important Gram-positive organisms, including those resistant to methicillin and glycopeptides. The chemical structure of linezolid is sketched in Figure 1. The oxazolidinones have an unique mode of action, which inhibits the initiation of the synthesis of bacterial proteins and enzymes, by preventing the formation of the ternary complex at 70S ribosomal subunit (Stevens et al 2004), by an apparent double blockade of both the 50S and the 30S bacterial ribosomal subunits. The uniquely particular mechanisms of action of linezolid, which includes a blockade of ribosomal assemblation which occurs before the initiation of bacterial protein synthesis (Stevens et al 2004), makes very improbable the emerging of cross resistance with other antimicrobial compounds. Single episodes of linezolid resistance have until now been anecdotally reported, especially after long-term and low-dosage courses, although it appears to be extremely rare among Staphylococci (Herrero et al 2002; Meka and Gold 2004), while linezolid-resistant Enterococci have been occasionally reported in intensive care units (Weigelt et al 2005), reports for both are now increasingly common.

Bottom Line: During the recent years, the phenomenon of multiresistant Gram-positive cocci is spreading to the community, where the retrieval of such microorganism is progressively increasing.The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains.The first oxazolidinone derivative linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin, and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds on the pipeline, represent an effective response to the great majority of these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, Division of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital Bologna, Italy.

ABSTRACT
Multi-antibiotic resistant Gram-positive cocci, which include Staphylococcus aureus, the coagulase-negative staphylococcal group, Enterococcus faecalis and Enterococcus faecium, and other streptococci, represent emerging pathogens especially in the setting of the immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are of concern, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics or immunosuppressive drugs are widely administered. During the recent years, the phenomenon of multiresistant Gram-positive cocci is spreading to the community, where the retrieval of such microorganism is progressively increasing. The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains. The first oxazolidinone derivative linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin, and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds on the pipeline, represent an effective response to the great majority of these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern. The main problems related to the epidemiological and clinical features of multiresistant Gram-positive infection, the potential clinical indications of all recently available compounds compared with the standard of care of treatment of resistant Gram-positive infections, and updated data on efficacy and tolerability of linezolid as the golden standard compound for vancomycin-resistant Gram-positive cocci in multiple clinical situations, are outlined and updated on the ground of an extensive review of all the available, recent evidences coming from the international literature.

No MeSH data available.


Related in: MedlinePlus