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Year : 2015  |  Volume : 33  |  Issue : 1  |  Page : 1--2

Need to rationalize linezolid use

A Kapil 
 Department of Microbiology , All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
A Kapil
Department of Microbiology (AK), All India Institute of Medical Sciences, New Delhi

How to cite this article:
Kapil A. Need to rationalize linezolid use.Indian J Med Microbiol 2015;33:1-2

How to cite this URL:
Kapil A. Need to rationalize linezolid use. Indian J Med Microbiol [serial online] 2015 [cited 2020 Jul 7 ];33:1-2
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Linezolid was introduced in clinical practice in the beginning of 21 st century and was considered to be an ideal reserve drug for treatment of vancomycin-resistant Enterococcus spp. (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). It has remained a promising antimicrobial against gram-positive cocci and no resistance was reported for a long time. Linezolid acts by inhibiting protein synthesis and the mode of action does not lead to cross resistance with other antimicrobials. Although bacterostatic in action, its bio-availably is 100% even with oral administration with excellent tissue distribution that leaves an option for early oral switch from intravenous administration. Also, it does not require dose adjustment for renal or hepatic impairment.

Even in treating methicillin-resistant Staphylococcus aureus (MRSA) where vancomycin has been the drug of choice, linezolid is a logical option for antibiotic de-escalation due to a possibility of oral switch in selected group of patients, resulting in early discharge of the patient from hospital. This is beneficial both to the patient and hospital as it could reduce the cost of treatment by reducing the hospital stay, which will further decrease exposure of patient to the healthcare setting and thus reduce risk of acquiring healthcare-associated infections.

Broadly looking at the emergence of resistance in gram-positive bacteria in a hospital microenvironment over the years, we know that increase vancomycin use has been responsible for emergence of vancomycin-resistant Enterococci (VRE), besides reports on VRSA or vancomycin intermediate resistant Staphylococcus aureus (VISA). With increasing infectious due to VRE, linezolid is the best option available.

The mechanism of resistance to linezolid is by mutations in 23S ribosomal ribonucleic acid (rRNA) or presence of cfr gene. Though mutations in 23S rRNA is more commonly reported in literature, it is not transferable and therefore the spread of resistance can be limited by standard precautions. The other transferable plasmid mediated cfr gene, also imparting multidrug resistance, has also been demonstrated in both MRSA and VRE.

Reports of resistance to linezolid along with the characterization of mechanism of resistance have been documented in Enterococcus sp., Staphylococcus sp. and MRSA. [1],[2],[3] From India, all Staphylococcus sp. and Enterococcus sp. remain linezolid sensitive except for occasional case reports. [4],[5] Recently, Staphylococcus sp. having both the mechanisms has been reported from India. [6]

A study by Rai et al., published in this issue [7] shows the presence of mutations G2576U in 23S rRNA in three isolates from a patient admitted to their hospital who was administered linezolid prior to admission. The patient had blood stream infection with linezolid resistant E. fecium (LRVRE). On surveillance cultures, the authors found that the gut of this patient was colonized with the same organism besides having nasal carriage of linezolid resistant S. aureus (LRMRSA). This emphasizes a need for continuous monitoring of the patients on linezolid by surveillance cultures for detection of LRVRE or LRMRSA.

As the more common mode of resistance by mutations in 23S rRNA are non-transferable, it is possible to control the dissemination of resistant clones by implementing infection control practices in healthcare settings. However, the other mechanism of cfr gene mediated resistance, which is transferable, is a cause of concern as we know that this resistance can be transferred horizontally across bacterial species. The ease of oral administration of linezolid can be easily exploited in clinical practice, especially its use in treating MRSA in a community setting. So, there is a need to emphasize the rational antibiotic use and keep linezolid as a reserve.


1Chamon RC, Iorio NL, Cavalcante FS, da Silva Teodoro CR, de Oliveira AP, Maia F, et al. Linezolid-resistant Staphylococcus haemolyticus and Staphylococcus hominis: Single and double mutations at the domain V of 23S rRNA among isolates from a Rio de Janeiro hospital. Diagn Microbiol Infect Dis 2014;80:307-10.
2Gopegui ER, Juan C, Zamorano L, Pérez JL, Oliver A. transferable multidrug resistance plasmid carrying cfr associated with tet (L), ant (4=)-Ia, and dfrK Genes from a Clinical Methicillin-Resistant Staphylococcus aureus ST125 Strain. Antimicrob Agents Chemother 2012;56:2139-42.
3Chena H, Wu W, Nic M, Liu Y, Zhange J, Xiaf F, et al. Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: Molecular epidemiology and resistance mechanisms. Int J Antimicrob Agents 2013;42:317-21.
4Peer MA, Nasir RA, Kakru DK, Fomda BA, Bashir G, Sheikh IA. Sepsis due to Linezolid resistant Staphylococcus chonii and Staphylococcus kloosii: First reposts of Linezolid resistance in coagulase negative staphylococci from India. Indian J Med Microbiol 2011;29:60-2.
5Kalawat U, Sharma KK, Reddy S. Linezolid - resistant Staphylococcus spp. at a tertiary care hospital of Andhra Pradesh. Indian J Med Microbiol 2011;29:314-5.
6Rajan V, Kumar VS, Gopal S. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid - resistance. Indian J Med Res 2014;139:463-7.
7Rai S, Niranjan DK, Kaur T, Singh NP, Hada V, Kaur IR. Detection of the classical G2576U mutation in linezolid resistant Staphylococcus aureus along with isolation of linezolid resistant Enterococcus faecium from a patient on short-term linezolid therapy: First report from India. Indian J Med Microbiol 2015;33.