Shimpi Chopra

Bio: Shimpi Chopra is an academic researcher from Vardhman Mahavir Medical College. The author has contributed to research in topics: Linezolid & 23S ribosomal RNA. The author has an hindex of 1, co-authored 1 publications receiving 9 citations.

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

Abstract: 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. 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. 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. 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.

Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.

Abstract: Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.

Epidemiology of Staphylococcus aureus Infections in Kenya: Current State, Gaps and Opportunities

Abstract: Staphylococcus aureus has maintained its clinical relevance as a major cause of hospital and community acquired infections globally with a high burden of antimicrobial resistance (AMR). Though reported, the burden of infection, antimicrobial resistance and molecular epidemiology of S. aureus are not well defined in Kenya. This descriptive review evaluated reported data on the detection and characterization of S. aureus infections in Kenya. Published data between 2000 and 2020 were evaluated. S. aureus isolation frequencies varied from 1% in blood specimens to 52.6% among skin and soft tissues infections while MRSA rates ranged from 1% to 84.1%. While penicillin resistance has consistently been high, last line and recent antibiotics such as vancomycin, linezolid, teicoplanin and daptomycin have retained their efficacy. Data on MRSA carriage in the community, among HCWs and inpatients is limited. Global clones (CC1, CC5, CC8, CC22, CC30, CC45 and CC239) alongside a few novel MRSA strains have been reported with staphylococcal protein A (spa) sequence based clustering yielding four major clusters (spa CC359, spa CC005, spa CC121 and spa CC021) in circulation. MRSA strain ST239/241 (t037) seems predominant in the country. Despite a clear paucity of data, the present analysis points to a high infection and AMR burden in S. aureus with global MRSA clones in circulation. Standardized national surveillance and reporting incorporating molecular tools for identification and characterization will help fill existing gaps in the understanding of the evolving epidemiology of MRSA infections.

Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci.

Abstract: Coagulase-negative staphylococci (CoNS) for a long time were considered avirulent constituents of the human and warm-blooded animal microbiota. However, at present, S. epidermidis, S. haemolyticus, and S. hominis are recognized as opportunistic pathogens. Although linezolid is not registered for the treatment of CoNS infections, it is widely used off-label, promoting emergence of resistance. Bioinformatic analysis based on maximum-likelihood phylogeny and Bayesian clustering of the CoNS genomes obtained in the current study and downloaded from public databases revealed the existence of international linezolid-resistant lineages, each of which probably had a common predecessor. Linezolid-resistant S. epidermidis sequence-type (ST) 2 from Russia, France, and Germany formed a compact group of closely related genomes with a median pairwise single nucleotide polymorphism (SNP) difference of fewer than 53 SNPs, and a common ancestor of this lineage appeared in 1998 (1986-2006) before introduction of linezolid in practice. Another compact group of linezolid-resistant S. epidermidis was represented by ST22 isolates from France and Russia with a median pairwise SNP difference of 40; a common ancestor of this lineage appeared in 2011 (2008-2013). Linezolid-resistant S. hominis ST2 from Russia, Germany, and Brazil also formed a group with a high-level genome identity with median 25.5 core-SNP differences; the appearance of the common progenitor dates to 2003 (1996-2012). Linezolid-resistant S. hominis isolates from Russia demonstrated associated resistance to teicoplanin. Analysis of a midpoint-rooted phylogenetic tree of the group confirmed the genetic proximity of Russian and German isolates; Brazilian isolates were phylogenetically distant. repUS5-like plasmids harboring cfr were detected in S. hominis and S. haemolyticus.

Molecular detection of chloramphenicol-florfenicol resistance (cfr) genes among linezolid resistant MRSA isolates in Sokoto State, Nigeria

Abstract: Objective : we investigated previous literatures for documentation of the trend in Sokoto, Nigeria and found none We deemed it fit to determine the frequency of linezolid resistance mediated by cfr gene among MRSA isolates from Sokoto State-owned hospitals Methods : Bacterial species identification was carried out with Microgen™ Staph-ID System kit (Microgen, Surrey, UK) Disc agar diffusion method (Modified Kirby-Bauer’s) following Clinical and Laboratory Standards Institute (CLSI 2018) guidelines was used in antimicrobial susceptibility testing The results were interpreted and managed using WHONET 56 software (WHO, Switzerland) Oxacillin resistant screening agar base (ORSAB) culture was used to determine phenotypic methicillin resistance Polymerase chain reaction (PCR) was carried out to determine the presence of cfr-gene Result s: A total of 81 S aureus isolates were phenotypically identified Of this number, 4691% (38/81) were MRSA; Healthcare workers (395%), Outpatient (289%), In patient (21%), Security men and Cleaners (53% each) Importantly linezolid resistance rate among the MRSA isolates was 447% Analysis of antimicrobial susceptibility profile also showed a multiple antibiotics resistance burden of MDR (59%), possible XDR (471%), XDR (411%) and PDR (59%) amongst LR-MRSA About 529% (9/17) of LR-MRSA harbored the cfr gene Conclusions : This is the first report to document cfr gene in LR-MRSA strains in Sokoto The cfr gene was found among the studied LR-MRSA strains and if cfr-mediated linezolid resistance is not properly checked, its phenotypic expression may result in an outbreak of multiple antibiotic resistant strains

Coagulase-Negative Staphylococci Clones Are Widely Distributed in the Hospital and Community.

Abstract: Coagulase-negative staphylococci (CoNS) may be considered contaminants when isolated from clinical specimens but may also be a cause of true infection. This study aimed to compare the clonality and SCCmec type of a collection of CoNS isolated from blood cultures of inpatients, nasal swabs of healthy individuals, and patients with chronic wounds, all from the same community, using SCCmec typing, pulsed-field gel electrophoresis (PFGE), and MLST. Staphylococcus epidermidis, exhibited high clonal diversity, but hospital and community clusters were observed. Nosocomial S. epidermidis clones belonged to sequence types ST2, ST6, and ST23. Some Staphylococcus haemolyticus clones were found to circulate in the hospital and community, while Staphylococcus saprophyticus exhibited very high clonal diversity. Staphylococcus lugdunensis, Staphylococcus warneri, and Staphylococcus capitis revealed several isolates belonging to the same clone in the hospital and community. The detection of different SCCmec types within the same cluster indicated high diversity. S. epidermidis was associated with SCCmec I and III, S. haemolyticus with I and II, S. capitis with type V, Staphylococcus hominis with mec complex type A and ccr1, and S. warneri and S. saprophyticus with SCCmec I. The generation of elements and new combinations of cassette genes were highly associated with CoNS isolates, suggesting that SCCmec may not be a good marker of clonality in these bacteria.