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Updated: Jan 20, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections
Gajanand Mittal1, Vasundhra Bhandari2, Rajni Gaind3
1Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, 110029, India.
Background:
Coagulase-negative Staphylococci (CoNS) have emerged as a major causative agent of blood-stream infections (BSI). Linezolid (LZD) is currently used for treating glycopeptide and methicillin-resistant staphylococci. It is important to understand the resistance mechanism and probable transmission of LZD resistant (LR) CoNS within the hospital.
Methods:
Clinically significant LRCoNS from patients with BSI were characterized using MALDI-TOF and 16S rRNA gene sequence analysis. Antimicrobial susceptibility and MIC of vancomycin and LZD were determined. LZD resistance mechanisms using PCR for the cfr gene and mutation in the V domain of the 23S rRNA gene were studied.
Results:
The MIC of LZD ranged from 8 to 32 μg/ml. LR was observed in three different CoNS species from diverse locations within the hospital. The cfr gene was identified in all the isolates. Sequence analysis of V domain region of 23S rRNA gene confirmed mutation in single copy among 12/15 isolates with novel mutations: G2614 T and C2384T. All infections were nosocomially acquired and LZD resistance was emerging in the absence of prior LZD use. Horizontal spread of resistant isolates and cfr gene among diverse species were the probable mechanisms of transmission.
Conclusion:
The study highlights the novel mutations associated with LRCoNS and the importance of surveillance & transmission pathway within the hospital. It also systematically discusses the published information on LRCoNS.
Insights
Linezolid-resistant Coagulase-negative Staphylococci (CoNS) infections are emerging due to novel mutations and horizontal gene transfer. Hospital surveillance is crucial to understand transmission pathways of these resistant bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Coagulase-negative Staphylococci (CoNS) are significant causes of bloodstream infections (BSI).
- Linezolid (LZD) is a critical treatment for resistant staphylococcal infections.
- Understanding Linezolid resistance (LR) in CoNS is vital for infection control.
Purpose of the Study:
- To characterize Linezolid-resistant CoNS (LRCoNS) from bloodstream infections.
- To investigate the genetic mechanisms and transmission of Linezolid resistance in CoNS.
- To identify novel mutations associated with Linezolid resistance.
Main Methods:
- Bacterial identification using MALDI-TOF and 16S rRNA sequencing.
- Antimicrobial susceptibility testing and Minimum Inhibitory Concentration (MIC) determination for Linezolid and vancomycin.
- Molecular analysis including PCR for the cfr gene and sequencing of the 23S rRNA gene for mutations.
Main Results:
- Linezolid resistance (MIC 8-32 μg/ml) was found in three CoNS species.
- The cfr gene was detected in all isolates; novel mutations (G2614T, C2384T) were identified in the 23S rRNA gene of 12/15 isolates.
- Nosocomial acquisition and horizontal spread of resistant isolates and the cfr gene were identified as probable transmission mechanisms, even without prior Linezolid use.
Conclusions:
- Novel mutations in the 23S rRNA gene are associated with Linezolid resistance in CoNS.
- Hospital surveillance and understanding transmission pathways are essential for managing LRCoNS.
- The study provides insights into the emergence and spread of Linezolid-resistant CoNS.
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