Linezolid-Resistant Staphylococcus haemolyticus: Emergence of G2447U and C2534U Mutations at the Domain V of 23Sr RNA Gene

Abstract

Background: Linezolid an oxazolidinone drug available in both parenteral and oral formulations has emerged as a novel alternative to vancomycin and other second-generation drugs for the treatment of infections from gram-positive cocci. Clinical isolates of linezolid-resistant staphylococci and enterococci were reported. Since then, linezolid-resistant strains have become an increasing problem worldwide. The most frequently reported mechanisms of linezolid resistance include the mutation in 23S ribosomal nucleic acid and presence of cfr gene. Methicillin-resistant coagulase-negative staphylococci (MR-CoNS) and vancomycin-resistant Enterococcus (VRE) have become a worrisome clinical problem. Objective: Therefore, we aimed to determine the distribution of linezolid-resistant strains in an inpatient setting of a tertiary-care hospital in India and to evaluate the resistance mechanisms among these isolates. In addition, the clonal diversity of the isolates was determined by pulsed-field gel electrophoresis (PFGE). Methods: The distribution, clonal diversity, and resistance mechanism of linezolid resistant-Staphylococcus haemolyticus (LRSH) strains were determined. The isolates were identified by MALDI-TOF. The mechanism of resistance was determined by sequence analysis of the domain V of 23SrRNA and screening for cfr gene. Clonal relatedness was defined by PFGE. Results: In total, 13 LRSH isolates were recovered from pus specimens. The 13 LRSH strains isolated had an linezolid MIC of 256 g/mL. Sequencing results revealed G2576T mutations in 7 (53.8%), G2447U in 4 (30.7%) and C2534U in 1 (7.6%) isolate of S. haemolyticus. One isolate of S. haemolyticus showed 2 simultaneous mutations (G2576T and G2447U) in the domain V region of 23Sr RNA gene. PFGE of the LR-SH isolates revealed the presence of 11 clones. Of the 11 clones, clones I and II had 2 isolates each. Isolates of clone I exhibited a band pattern identical with the previous isolates of LRSH isolated from the orthopedic unit. Similarly, isolates of clone II also shared the same band pattern with the previous LRSH isolates from the dermatology unit of our center. Conclusions: This study highlights the importance of continuous monitoring of vigilance of linezolid resistance in staphylococci. Rationalizing the use of linezolid and implementing methods to control the spread of hospital clones is of paramount importance to prevent further dissemination of these strains.Funding: NoneDisclosures: None