scholarly journals First Report of cfr-Mediated Resistance to Linezolid in Human Staphylococcal Clinical Isolates Recovered in the United States

2008 ◽  
Vol 52 (6) ◽  
pp. 2244-2246 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Lalitagauri M. Deshpande ◽  
Mariana Castanheira ◽  
Joseph DiPersio ◽  
Michael A. Saubolle ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Ribosomal Protein ◽  
Staphylococcus Epidermidis ◽  
The United States ◽  
Human Infection ◽  
Clinical Isolates ◽  
23S Rrna ◽  
First Report ◽  
Linezolid Resistance

ABSTRACT Linezolid resistance has dominantly been mediated by mutations in 23S rRNA or ribosomal protein L4 genes. Recently, cfr has demonstrated the ability to produce a phenotype of resistance to not only oxazolidinones, but also other antimicrobial classes (phenicols, lincosamides, pleuromutilins, and streptogramin A). We describe the first detection of cfr-mediated linezolid resistance in Staphylococcus aureus and Staphylococcus epidermidis recovered from human infection cases monitored during the 2007 LEADER Program.

scholarly journals Polyphyletic Emergence of Linezolid-Resistant Staphylococci in the United States

2010 ◽  
Vol 54 (2) ◽  
pp. 742-748 ◽  
Author(s):  
Agnes Wong ◽  
Shilpa P. Reddy ◽  
Davida S. Smyth ◽  
Maria E. Aguero-Rosenfeld ◽  
George Sakoulas ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Epidermidis ◽  
The United States ◽  
23S Rrna ◽  
Resistance Mutations ◽  
Gene Characterization ◽  
Linezolid Resistance ◽  
Year 2000 ◽  
Gram Positive Cocci

ABSTRACT Since the year 2000, linezolid has been used in the United States to treat infections caused by antimicrobial-resistant Gram-positive cocci. At present, linezolid-resistant (Linr) Staphylococcus aureus and Staphylococcus epidermidis strains are rare and the diversity of their genetic backgrounds is unknown. We performed sequence-based strain typing and resistance gene characterization of 46 Linr isolates that were collected from local and national sources between the years 2004 and 2007. Resistance was found to occur in at least three clonal complexes (CCs; lineages) of S. aureus and in at least four subclusters of a predominant, phylogenetically unstable CC of S. epidermidis. New candidate resistance mutations in 23S rRNA and the L4 riboprotein were identified among the S. epidermidis isolates. These findings suggest that linezolid resistance has emerged independently in multiple clones of S. aureus and with a variety of ribosomal mutations in multiple clones of S. epidermidis.

scholarly journals Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Jennifer M. Streit ◽  
Patricia A. Hogan ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Resistance Mechanisms ◽  
23S Rrna ◽  
Rrna Gene ◽  
Gram Positive ◽  
Content Type ◽  
Linezolid Resistance

ABSTRACT This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus, inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, especially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.

scholarly journals Mutations within therplDGene of Linezolid-Nonsusceptible Streptococcus pneumoniae Strains Isolated in the United States

2014 ◽  
Vol 58 (4) ◽  
pp. 2459-2462 ◽  
Author(s):  
W. Dong ◽  
S. Chochua ◽  
L. McGee ◽  
D. Jackson ◽  
K. P. Klugman ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Structural Changes ◽  
Binding Pocket ◽  
The United States ◽  
Target Site ◽  
23S Rrna ◽  
Content Type

ABSTRACTThree invasiveStreptococcus pneumoniaestrains nonsusceptible to linezolid were isolated in the United States between 2001 and 2012 from the CDC's Active Bacterial Core surveillance. Linezolid binds ribosomal proteins where structural changes within its target site may confer resistance. Our study identified mutations and deletions near the linezolid binding pocket of two of these strains within therplDgene, which encodes ribosomal protein L4. Mutations in the 23S rRNA alleles or therplVgene were not detected.

scholarly journals Predominance of 23S rRNA Mutants among Non-Erm, Non-Mef Macrolide-Resistant Clinical Isolates of Streptococcus pneumoniae Collected in the United States in 1999-2000

2005 ◽  
Vol 49 (7) ◽  
pp. 3031-3033 ◽  
Author(s):  
Todd A. Davies ◽  
Karen Bush ◽  
Daniel Sahm ◽  
Alan Evangelista
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Gene Mutations ◽  
The United States ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Surveillance Studies

ABSTRACT A total of 322 erythromycin-resistant pneumococci from TRUST 3 and TRUST 4 United States surveillance studies (1999-2000) were screened for 23S rRNA, L4, and L22 gene mutations. Nineteen isolates, two with mefA, had mutations at position 2058 or 2059 in 23S rRNA. Two had a 69GTG71-to-TPS substitution in L4; one of these also contained ermA.

scholarly journals LEADER Program Results for 2009: an Activity and Spectrum Analysis of Linezolid Using 6,414 Clinical Isolates from 56 Medical Centers in the United States

2011 ◽  
Vol 55 (8) ◽  
pp. 3684-3690 ◽  
Author(s):  
David J. Farrell ◽  
Rodrigo E. Mendes ◽  
James E. Ross ◽  
Helio S. Sader ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Geographic Area ◽  
The United States ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Coagulase Negative Staphylococci ◽  
Laboratory Design ◽  
Linezolid Resistance ◽  
Medical Centers

ABSTRACTThe LEADER Program monitors thein vitroactivity of linezolid in sampled U.S. medical centers using reference broth microdilution methods with supporting molecular investigations in a central laboratory design. This report summarizes data obtained in 2009, the 6th consecutive year of this longitudinal study. A total of 6,414 isolates from 56 medical centers in all nine Census regions across the United States participated in 2009. For the six leading species/groups, the following linezolid MIC90values were observed:Staphylococcus aureus, 2 μg/ml; coagulase-negative staphylococci (CoNS), 1 μg/ml;Enterococcusspp., 2 μg/ml;Streptococcus pneumoniae, 1 μg/ml; viridans group streptococci, 1 μg/ml; and beta-hemolytic streptococci, 1 μg/ml. Linezolid resistance was only 0.34% overall, with no evidence of significant increase in the LEADER Program since 2006. The predominant linezolid resistant mechanism found was a G2576T mutation in the 23S rRNA. L3/L4 riboprotein mutations were also found. The mobile multidrug-resistantcfrgene was found in four strains (twoS. aureusstrains and one strain each ofS. epidermidisandS. capitis) from four different states, suggesting persistence but a lack of dissemination. Linezolid continues to exhibit excellent activity and spectrum, and this study documents the need for continued monitoring of emerging mechanisms of resistance over a wide geographic area.

scholarly journals First Report ofcfr-Carrying Plasmids in the Pandemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Staphylococcal Cassette ChromosomemecType IV Clone

2016 ◽  
Vol 60 (5) ◽  
pp. 3007-3015 ◽  
Author(s):  
Anna C. Shore ◽  
Alexandros Lazaris ◽  
Peter M. Kinnevey ◽  
Orla M. Brennan ◽  
Gráinne I. Brennan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ribosomal Proteins ◽  
Resistance Mechanisms ◽  
Sequence Type ◽  
23S Rrna ◽  
Methicillin Resistant ◽  
Content Type ◽  
First Report ◽  
Type Iv ◽  
Linezolid Resistance

ABSTRACTLinezolid is often the drug of last resort for serious methicillin-resistantStaphylococcus aureus(MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins;cfr, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPSA) resistance; its homologuecfr(B); oroptrA, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare inS. aureus, andcfris even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected tocfrPCR, PhLOPSAsusceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling,spatyping, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification,cfrplasmid sequence analysis, andoptrAandcfr(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosomemectype IV (ST22-MRSA-IV)/spatype t032 isolates, harboredcfr, exhibited the PhLOPSAphenotype, and lackedoptrAandcfr(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harboredcfrandfexAon a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harboredcfrandlsa(B) on a novel 27-kb plasmid. This is the first report ofcfrin the pandemic ST22-MRSA-IV clone. Differentcfrplasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential.

scholarly journals Macrolide Resistance by Ribosomal Mutation in Clinical Isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 Study

2003 ◽  
Vol 47 (6) ◽  
pp. 1777-1783 ◽  
Author(s):  
D. J. Farrell ◽  
S. Douthwaite ◽  
I. Morrissey ◽  
S. Bakker ◽  
J. Poehlsgaard ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
The United States ◽  
Resistance Mechanisms ◽  
Macrolide Resistance ◽  
Primer Extension ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Resistant Organism ◽  
Rrna Methylation

ABSTRACT Sixteen (1.5%) of the 1,043 clinical macrolide-resistant Streptococcus pneumoniae isolates collected and analyzed in the 1999-2000 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study have resistance mechanisms other than rRNA methylation or efflux. We have determined the macrolide resistance mechanisms in all 16 isolates by sequencing the L4 and L22 riboprotein genes, plus relevant segments of the four genes for 23S rRNA, and the expression of mutant rRNAs was analyzed by primer extension. Isolates from Canada (n = 4), Japan (n = 3), and Australia (n = 1) were found to have an A2059G mutation in all four 23S rRNA alleles. The Japanese isolates additionally had a G95D mutation in riboprotein L22; all of these originated from the same collection center and were clonal. Three of the Canadian isolates were also clonal; the rest were not genetically related. Four German isolates had A2059G in one, two, and three 23S rRNA alleles and A2058G in two 23S rRNA alleles, respectively. An isolate from the United States had C2611G in three 23S rRNA alleles, one isolate from Poland had A2058G in three 23S rRNA alleles, one isolate from Turkey had A2058G in four 23S rRNA alleles, and one isolate from Canada had A2059G in two 23S rRNA alleles. Erythromycin and clindamycin resistance gradually increased with the number of A2059G alleles, whereas going from one to two mutant alleles caused sharp rises in the azithromycin, roxithromycin, and rokitamycin MICs. Comparisons of mutation dosage with rRNA expression indicates that not all alleles are equally expressed. Despite their high levels of macrolide resistance, all 16 isolates remained susceptible to the ketolide telithromycin (MICs, 0.015 to 0.25 μg/ml).

scholarly journals Comparison of BD Max StaphSR and BD Max MRSAXTfor Screening of Staphylococcus aureus Clinical Isolates Collected from Hospitals in the United States: TABLE 1

2016 ◽  
Vol 54 (6) ◽  
pp. 1668-1669
Author(s):  
Rodrigo E. Mendes ◽  
Amy A. Watters ◽  
Paul R. Rhomberg ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Clinical Isolates

scholarly journals Characterization of Erythromycin-Resistant Isolates of Staphylococcus aureus Recovered in the United States from 1958 through 1969

1998 ◽  
Vol 42 (11) ◽  
pp. 3024-3027 ◽  
Author(s):  
Federico G. Nicola ◽  
Linda K. McDougal ◽  
James W. Biddle ◽  
Fred C. Tenover
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Single Copy ◽  
The United States ◽  
Clinical Isolates ◽  
Constitutive Resistance

ABSTRACT We tested 16 erythromycin-resistant clinical isolates of S. aureus, recovered from patients hospitalized in the United States from 1958 to 1969, for the presence of ermA,ermB, and ermC by using PCR. Fifteen of 16 isolates contained at least one copy of ermA; the remaining isolate, which was also clindamycin resistant, containedermB. Eight of the 15 isolates harboring ermA, all of which were inducible, contained a single copy of the gene in the chromosome, while the remaining seven isolates had two copies of the gene. ermB was plasmid encoded and mediated constitutive resistance to erythromycin.

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