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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Infect Dis. May 25, 2015; 5(2): 14-29
Published online May 25, 2015. doi: 10.5495/wjcid.v5.i2.14
Treatment of methicillin-resistant Staphylococcus aureus infections: Importance of high vancomycin minumum inhibitory concentrations
Alejandra Morales-Cartagena, Antonio Lalueza, Francisco López-Medrano, Rafael San Juan, José María Aguado
Alejandra Morales-Cartagena, Antonio Lalueza, Francisco López-Medrano, José María Aguado, Rafael San juan, Infectious Diseases Unit, Department of Medicine, University Hospital 12 de Octubre, 28041 Madrid, Spain
Author contributions: Morales-Cartagena A and Lalueza A were the main authors in writing the draft version; López-Medrano F and Aguado JM principal physicians involved in the critical revision of the manuscript; all the authors approved the final version of the manuscript.
Conflict-of-interest: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Alejandra Morales-Cartagena, Infectious Diseases Unit, Department of Medicine, University Hospital 12 de Octubre, Av. Córdoba km 5.400, 28041 Madrid, Spain. a.morales.cartagena@gmail.com
Telephone: +34-91-3908247 Fax: +34-91-3908112
Received: July 3, 2014
Peer-review started: July 4, 2014
First decision: July 29, 2014
Revised: February 26, 2015
Accepted: March 5, 2015
Article in press: March 9, 2015
Published online: May 25, 2015
Processing time: 319 Days and 18.1 Hours
Abstract

Staphylococcus aureus (SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threatening systemic infections. The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration (MIC) (dubbed the MIC “creep”). In this way, the emergence of vancomycin-intermediate SA (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant SA. These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach. Ultimately, various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range (i.e., MIC = 2 μg/mL). These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use, both in methicillin-resistant SA and in methicillin-sensitive SA. The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains, and the different optimal treatment options known.

Keywords: Staphylococcus aureus; Minimum inhibitory concentration; Methicillin-resistant Staphylococcus aureus; Vancomycin-intermediate Staphylococcus aureus; Heteroresistant-vancomycin-intermediate Staphylococcus aureus; Vancomycin resistant Staphylococcus aureus

Core tip: The emergence of increasing vancomycin-resistance in Staphylococcus aureus (SA) isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. Complete vancomycin-resistance is acquired through plasmid transmission of enterococcal gene vanA. However, the development of strains with gradual loss of vancomycin-susceptibility seems to be related to conformational bacterial changes and affects its pathogenicity and even its susceptibility to other antimicrobials (other than vancomycin). It has been observed that the impact of diminished vancomycin susceptibility could not only affect methicillin-resistant SA but has also been related to worse prognosis in methicillin-sensitive SA infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.