Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections (BSI) in India

Abstract

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 gen e 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.

Antibiotic resistance properties of Staphylococcus epidermidis isolated from hospitals in Selangor

“…This is similar to studies conducted on clinical S. epidermidis isolates in India and Italy [13,55]. This finding is also in agreement with the claim of the significance of linezolid in the treatment for S. epidermidis infections [33], whereby it is used for treatment in cases of glycopeptideresistant infections [29,56]. However, there were also isolated cases on resistant strains of S. epidermidis when tested against linezolid in India and Saudi Arabia [15,36].…”

Epidemiology of <i>Staphylococcus aureus</i> Infections in Kenya: Current State, Gaps and Opportunities

“…However, resistance against linezolid, mediated by point mutations and the plasmid-borne chloramphenicol florfenicol resistance (cfr) gene has already been observed in other settings [43]. The cfr gene has also been implicated in phenotypic expression of resistance against other classes such as lincosamides and phenicols [44]. Resistance against daptomycin, mediated by a variety of mechanisms is increasingly being recognized in S. aureus [45].…”

“…Initial observation of resistance coupled with the expiry of patents for the two drugs and their impending decreased costs and greater availability calls for vigilance through constant surveillance for emerging resistant strains as prolonged use has been suggested as a key driver of linezolid resistance. The threat of widespread resistance is compounded by the occurrence of linezolid and high level daptomycin resistance among coagulase negative Staphylococci [44] which may act as a pool of resistance genes for the more pathogenic S. aureus [46].…”

First Case of Staphylococci Carrying Linezolid Resistance Genes from Laryngological Infections in Poland

“…The first linezolid-resistant S. haemolyticus (LRSH) strain was reported by Rodríguez-Aranda et al in 2009 [ 8 ]. Since then, a few strains (namely, 11) have been reported worldwide [ 9 , 10 ], but most of them were reported from China [ 11 , 12 ] and from India [ 13 , 14 , 15 ], with the last one in 2019 [ 16 ].…”

“…Linezolid resistance has also emerged in patients without linezolid exposure, which is probably due to cross-transmission between patients, horizontal transfer of linezolid resistance mediated by transferable genes among different CoNS species or co-selection by treatment with other antibiotics [ 15 , 22 ]. Moreover, linezolid-resistant strains are also resistant to other groups of antibiotics, especially linezolid resistant strains are often simultaneously resistant to β lactams, so a proper characterization of broad resistance mechanisms is required [ 29 ].…”