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The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid.
Curr Med Res Opin 2010; 26(3):571-88CM

Abstract

BACKGROUND

The rising prevalence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) and the recent emergence of community-associated MRSA are major clinical, public health, and economic challenges. MRSA is a leading cause of nosocomial pneumonia and complicated skin and soft-tissue infections (cSSTI). Vancomycin and linezolid are two commonly used antimicrobial agents with activity against Gram-positive pathogens, particularly MRSA, that are used to treat both nosocomial pneumonia and cSSTI. Recently, the therapeutic efficacy of vancomycin in the treatment of hospitalized patients with MRSA infections has been questioned due to the emergence of MRSA strains with reduced susceptibility to vancomycin together with concerns related to inadequate dosing and poor tissue penetration of the drug.

SCOPE

A literature review was conducted to investigate the pharmacokinetics and pulmonary and tissue penetration of vancomycin and linezolid. Using MEDLINE and EMBASE, the most relevant articles in English published over the past 25 years (up to October 2008) were identified and summarized. Studies in human volunteers and adult patients that measured concentrations of antibiotic in serum, epithelial lining fluid (ELF), and tissue were selected for further review.

FINDINGS

For both drugs, pharmacokinetic studies were conducted in diverse patient populations and employed varying techniques to measure tissue concentrations. Vancomycin concentrations in ELF ranged from 5 to 25% of simultaneous plasma levels, while concentrations in whole homogenized lung tissue were slightly higher (24-41%). Distribution of vancomycin into soft tissue was variable. For linezolid, overall mean concentrations in ELF and in soft tissue were generally similar or higher than simultaneous plasma levels, although variability in tissue penetration across studies in healthy volunteers and patients was seen.

LIMITATIONS

The studies included in this review vary greatly in their designs and patient populations; this, together with methodologic difficulties, limits the interpretation of the data.

CONCLUSIONS

In the absence of clinical data correlating ELF concentrations and clinical outcome, the clinical significance of differences in pulmonary penetration of vancomycin and linezolid is unknown. Higher vancomycin serum concentrations may be necessary to achieve appropriate lung concentrations to optimize treatment outcomes. Linezolid demonstrates adequate penetration into lung and other soft issues with sustained concentrations above the minimum inhibitory concentrations for susceptible pathogens, including MRSA, for the majority of the dosing interval. Examination of the pharmacokinetic data adds insights not provided by the clinical trial data and together provides clinicians with a more comprehensive basis for selecting appropriate antimicrobial therapy for the treatment of serious MRSA infections.

Authors+Show Affiliations

Department of Medicine, Michigan State University, East Lansing, MI, USA. steing@msu.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20055750

Citation

Stein, Gary E., and Elizabeth M. Wells. "The Importance of Tissue Penetration in Achieving Successful Antimicrobial Treatment of Nosocomial Pneumonia and Complicated Skin and Soft-tissue Infections Caused By Methicillin-resistant Staphylococcus Aureus: Vancomycin and Linezolid." Current Medical Research and Opinion, vol. 26, no. 3, 2010, pp. 571-88.
Stein GE, Wells EM. The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid. Curr Med Res Opin. 2010;26(3):571-88.
Stein, G. E., & Wells, E. M. (2010). The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid. Current Medical Research and Opinion, 26(3), pp. 571-88. doi:10.1185/03007990903512057.
Stein GE, Wells EM. The Importance of Tissue Penetration in Achieving Successful Antimicrobial Treatment of Nosocomial Pneumonia and Complicated Skin and Soft-tissue Infections Caused By Methicillin-resistant Staphylococcus Aureus: Vancomycin and Linezolid. Curr Med Res Opin. 2010;26(3):571-88. PubMed PMID: 20055750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid. AU - Stein,Gary E, AU - Wells,Elizabeth M, PY - 2010/1/9/entrez PY - 2010/1/9/pubmed PY - 2010/5/21/medline SP - 571 EP - 88 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 26 IS - 3 N2 - BACKGROUND: The rising prevalence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) and the recent emergence of community-associated MRSA are major clinical, public health, and economic challenges. MRSA is a leading cause of nosocomial pneumonia and complicated skin and soft-tissue infections (cSSTI). Vancomycin and linezolid are two commonly used antimicrobial agents with activity against Gram-positive pathogens, particularly MRSA, that are used to treat both nosocomial pneumonia and cSSTI. Recently, the therapeutic efficacy of vancomycin in the treatment of hospitalized patients with MRSA infections has been questioned due to the emergence of MRSA strains with reduced susceptibility to vancomycin together with concerns related to inadequate dosing and poor tissue penetration of the drug. SCOPE: A literature review was conducted to investigate the pharmacokinetics and pulmonary and tissue penetration of vancomycin and linezolid. Using MEDLINE and EMBASE, the most relevant articles in English published over the past 25 years (up to October 2008) were identified and summarized. Studies in human volunteers and adult patients that measured concentrations of antibiotic in serum, epithelial lining fluid (ELF), and tissue were selected for further review. FINDINGS: For both drugs, pharmacokinetic studies were conducted in diverse patient populations and employed varying techniques to measure tissue concentrations. Vancomycin concentrations in ELF ranged from 5 to 25% of simultaneous plasma levels, while concentrations in whole homogenized lung tissue were slightly higher (24-41%). Distribution of vancomycin into soft tissue was variable. For linezolid, overall mean concentrations in ELF and in soft tissue were generally similar or higher than simultaneous plasma levels, although variability in tissue penetration across studies in healthy volunteers and patients was seen. LIMITATIONS: The studies included in this review vary greatly in their designs and patient populations; this, together with methodologic difficulties, limits the interpretation of the data. CONCLUSIONS: In the absence of clinical data correlating ELF concentrations and clinical outcome, the clinical significance of differences in pulmonary penetration of vancomycin and linezolid is unknown. Higher vancomycin serum concentrations may be necessary to achieve appropriate lung concentrations to optimize treatment outcomes. Linezolid demonstrates adequate penetration into lung and other soft issues with sustained concentrations above the minimum inhibitory concentrations for susceptible pathogens, including MRSA, for the majority of the dosing interval. Examination of the pharmacokinetic data adds insights not provided by the clinical trial data and together provides clinicians with a more comprehensive basis for selecting appropriate antimicrobial therapy for the treatment of serious MRSA infections. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/20055750/The_importance_of_tissue_penetration_in_achieving_successful_antimicrobial_treatment_of_nosocomial_pneumonia_and_complicated_skin_and_soft_tissue_infections_caused_by_methicillin_resistant_Staphylococcus_aureus:_vancomycin_and_linezolid_ L2 - http://www.tandfonline.com/doi/full/10.1185/03007990903512057 DB - PRIME DP - Unbound Medicine ER -