An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit

Kelly, Simon P.; Collins, Jonathan; Maguire, Maureen G.; Gowing, Catriona; Flanagan, Michelle; Donnelly, Maria; Murphy, Philip G.

doi:10.1093/jac/dkn043

Cited by 71 publications

(48 citation statements)

References 30 publications

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“…Several mutations have been pinpointed in the 23S rRNA, but the most common mutation is G2576T when using the Escherichia coli numbering system (for review, see . The same mutations were also observed in clinical isolates of S. aureus (Tsiodras et al 2001;, Staphylococcus epidermidis (Hong et al 2007;Kelly et al 2008), and in enterococci (Gonzales et al 2001;Sinclair et al 2003;Bourgeois-Nicolaos et al 2007) resistant to linezolid. There are four to six copies of the 23S rRNA genes in most gram-positive pathogens, and the level of resistance generally correlates with the number of mutated copies of 23S rRNA, as shown in the enterococci (Marshall et al 2002;Ruggero et al 2003) and in the staphylococci (Tsakris et al 2007;Besier et al 2008).…”

supporting

confidence: 58%

Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance

Feng¹,

Lupien²,

Gingras³

et al. 2009

Genome Res.

103

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Linezolid is a member of a novel class of antibiotics, with resistance already being reported. We used whole-genome sequencing on three independent Streptococcus pneumoniae strains made resistant to linezolid in vitro in a step-by-step fashion. Analysis of the genome assemblies revealed mutations in the 23S rRNA gene in all mutants including, notably, G2576T, a previously recognized resistance mutation. Mutations in an additional 31 genes were also found in at least one of the three sequenced genomes. We concentrated on three new mutations that were found in at least two independent mutants. All three mutations were experimentally confirmed to be involved in antibiotic resistance. Mutations upstream of the ABC transporter genes spr1021 and spr1887 were correlated with increased expression of these genes and neighboring genes of the same operon. Gene inactivation supported a role for these ABC transporters in resistance to linezolid and other antibiotics. The hypothetical protein spr0333 contains an RNA methyltransferase domain, and mutations within that domain were found in all S. pneumoniae linezolid-resistant strains. Primer extension experiments indicated that spr0333 methylates G2445 of the 23S rRNA and mutations in spr0333 abolished this methylation. Reintroduction of a nonmutated version of spr0333 in resistant bacteria reestablished G2445 methylation and led to cells being more sensitive to linezolid and other antibiotics. Interestingly, the spr0333 ortholog was also mutated in a linezolid-resistant clinical Staphylococcus aureus isolate. Whole-genome sequencing and comparative analyses of S. pneumoniae resistant isolates was useful for discovering novel resistance mutations.

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supporting

confidence: 58%

Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance

Feng¹,

Lupien²,

Gingras³

et al. 2009

Genome Res.

103

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“…The first linezolid-resistant clinical isolate was reported in an MRSA isolate in the USA (Tsiodras et al, 2001). Since then, the occurrence of linezolid-resistant staphylococci has been increasingly reported in the United States (Mendes et al, 2008;Scheetz et al, 2008), Mexico (Mendes et al, 2010a), Japan (Ikeda-Dantsuji et al, 2011), Italy (Bongiorno et al, 2010;Mendes et al, 2010b), Spain (Sánchez García et al 2010;Seral et al, 2011) and Ireland (Kelly et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of cfr-positive Staphylococcus aureus isolates from community-onset infectious patients in a county hospital in China

Zhao

Zheng

et al. 2015

Journal of Medical Microbiology

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The cfr gene was detected in 14 meticillin-susceptible Staphylococcus aureus isolates recovered from outpatients with community-onset infections in a county hospital in China. The MIC of linezolid was 4 mg ml 21 in eight isolates and 2 mg ml 21 in six isolates. All isolates were susceptible to vancomycin and teicoplanin, but had elevated MICs for penicillin (0.5-128 mg ml 21), chloramphenicol (2-32 mg ml 21), clindamycin (0.5-128 mg ml 21) and erythromycin (4-128 mg ml 21 ). Nine isolates had mutations on domain V of 23S rRNA and/or the ribosomal L proteins that were not located close to the linezolid-binding pocket. Southern blotting experiments demonstrated that the cfr genes in all 14 isolates resided on plasmids. Sequence analysis of the 5.6 kb cfr-carrying plasmid segment revealed 99 % identity to the corresponding sequences in plasmid pSS-01 from animal staphylococci and plasmid pRM-01 from human staphylococci. Five isolates belonged to sequence type (ST)188 and three to ST965; the two ST types were previously reported in isolates of animal origin in some areas of China. These results indicate that the cfr-carrying plasmids in this study are likely of animal origin. The present study shows that cfr-harbouring S. aureus isolates have emerged in some areas of China and that cfr-carrying isolates may be transmitted between animals and humans.

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“…Linezolid resistance occurred in < 1% of Staphylococcus aureus, coagulase-negative staphylococci, and enterococci isolates from the US between 2002 and 2009 [29] . Resistance usually develops after prolonged therapy with linezolid for serious infection although nosocomial acquisition of both resistant enterococci has been reported, including cases in patients with no prior treatment with linezolid [30][31][32] . It has been proposed that a combination with a second antibacterial agent, particularly rifampicin or fusidic acid, may delay the emergence of linezolid resistance in Staphylococcus aureus [33] .…”

Section: Joel J Et Al Linezolid In Orthopaedic Infectionsmentioning

confidence: 99%

Clinical results of linezolid in arthroplasty and trauma related infections

Graham

Peckham‐Cooper

et al. 2014

WJO

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AIM:To analyse the management of patients treated with linezolid for orthopaedic infections. METHODS:Twenty-two patients with orthopaedic related infections receiving a course of linezolid were reviewed retrospectively. Patients were classified into either post trauma, post arthroplasty and non trauma related infections. A diagnosis of infection was based on clinical findings, positive microbiological specimens, and positive signs of infection on radiological imaging and raised inflammatory markers. Pathogens isolated, inflammatory markers both at presentation and at final follow up, length of linezolid treatment, adverse drug reactions, concomitant anti-microbial therapy, length of hospital stay and any surgical interventions were recorded. RESULTS:Infections were classified as post arthroplasty (n = 10), post trauma surgery (n = 8) or nontrauma related infections (n = 4). Twenty patients (91%) underwent surgical intervention as part of their treatment. The number of required surgical procedures ranged from 1 to 6 (mean = 2.56). Mean total length of stay per admission was 28.5 d (range 1-160 d). Furthermore, the mean duration of treatment with linezolid of patients who had resolution of symptoms was 31 d (range 10-84 d). All patients within this group were discharged on oral linezolid. Pathogens isolated included methicillin resistant Staphylococcus aureus, coagulase negative staphylococci, coliforms, enterococcus, Staphylococcus epidermidis, streptococcus viridans, Escherichia coli, group B streptococcus and pseudomonas. An overall 77% of patients demonstrated resolution of infections at follow-up, with mean C-reactive protein reducing from 123 mg/L to 13.2 mg/L. CONCLUSION:This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Antibiotic resistance; Linezolid; Orthopaedic infections; Osteomyelitis; Periprosthetic joint infection Core tip: Our study demonstrates that linezolid delivers excellent oral bioavailability, with good penetration into bone, joints and soft tissue. It exhibits action against gram-positive organisms, including methicillin resistant Staphylococcus aureus and vancomycin resistant enterococci, and it is ideally suited for the variety of infections encountered in orthopaedic practice. Used in conjunction with surgical management, excellent results can be achieved in resolving infection.

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An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit

Cited by 71 publications

References 30 publications

Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance

Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance

Identification and characterization of cfr-positive Staphylococcus aureus isolates from community-onset infectious patients in a county hospital in China

Clinical results of linezolid in arthroplasty and trauma related infections

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