Linezolid resistance in a clinical isolate of Staphylococcus aureus

Tsiodras, Sotirios; Gold, Howard S.; Sakoulas, George; Eliopoulos, George M.; Wennersten, Christine; Venkataraman, Lata; Moellering, Robert C.; Ferraro, Mary Jane

doi:10.1016/s0140-6736(01)05410-1

Cited by 924 publications

(612 citation statements)

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“…have been associated with bacteremia and endocarditis for which therapy may be problematic; others have been associated with vaginal health, while depletion has been associated with an increased risk of urinary tract infections and bacterial vaginosis (1,12,14). In our study, many Lactobacillus species that were resistant to vancomycin, linezolid, and daptomycin were generally susceptible to telavancin at concentrations of Յ0.25 g/ml.…”

Section: Resultsmentioning

confidence: 55%

“…The development of resistance in gram-positive organismsincluding Staphylococcus aureus resistant to oxacillin and vancomycin (10,11,13) and linezolid (12) and vancomycinresistant enterococci also resistant to linezolid (4)-has accentuated the need for new antimicrobial agents. Telavancin is a novel glycopeptide that is bactericidal and shows concentration-dependent killing against gram-positive aerobes, including vancomycin-resistant strains (9).…”

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confidence: 99%

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In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp

Goldstein

Citron²,

Merriam³

et al. 2004

Antimicrob Agents Chemother

100

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Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca 2؉ to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC 90 s) for telavancin and vancomycin were as follows: Actinomyces spp. (n ‫؍‬ 45), 0.25 and 1 g/ml, respectively; Clostridium difficile (n ‫؍‬ 14), 0.25 and 1 g/ml, respectively; Clostridium ramosum (n ‫؍‬ 16), 1 and 4 g/ml, respectively; Clostridium innocuum (n ‫؍‬ 15), 4 and 16 g/ml, respectively; Clostridium clostridioforme (n ‫؍‬ 15), 8 and 1 g/ml, respectively; Eubacterium group (n ‫؍‬ 33), 0.25 and 2 g/ml, respectively; Lactobacillus spp. (n ‫؍‬ 26), 0.5 and 4 g/ml, respectively; Propionibacterium spp. (n ‫؍‬ 34), 0.125 and 0.5 g/ml, respectively; Peptostreptococcus spp. (n ‫؍‬ 52), 0.125 and 0.5 g/ml, respectively; and Corynebacterium spp. (n ‫؍‬ 31), 0.03 and 0.5 g/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three-to fivefold more active. Daptomycin had decreased activity (MIC > 4 g/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 g/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin-tazobactam were active against >98% of strains. The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei were >1 g/ml. The MIC 90 of TD-6424 for all strains tested was <2 g/ml. TD-6424 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.The development of resistance in gram-positive organismsincluding Staphylococcus aureus resistant to oxacillin and vancomycin (10,11,13) and linezolid (12) and vancomycinresistant enterococci also resistant to linezolid (4)-has accentuated the need for new antimicrobial agents. Telavancin is a novel glycopeptide that is bactericidal and shows concentration-dependent killing against gram-positive aerobes, including vancomycin-resistant strains (9). Unlike vancomycin, TD-6424 has multiple synergistic mechanisms of action resulting in TD-6424's enhanced activity against aerobic gram-positive species (5a, 9). At the MIC, it has exhibited postantibiotic effects of up to 6 h against S. aureus, compared to 2 h for vancomycin (9). TD-6424 is currently in phase 2 trials for serious gram-positive infe...

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Section: Resultsmentioning

confidence: 55%

mentioning

confidence: 99%

In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp

Goldstein

Citron²,

Merriam³

et al. 2004

Antimicrob Agents Chemother

100

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“…Linezolid is currently approved for the treatment of infections caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) strains and vancomycin-resistant enterococci. Resistance has developed sporadically during therapy in both enterococci (8) and S. aureus (29). The most common mechanism of linezolid resistance involves mutations in the central loop of domain V of the 23S rRNA.…”

mentioning

confidence: 99%

“…The most common mechanism of linezolid resistance involves mutations in the central loop of domain V of the 23S rRNA. The most frequent mutation associated with linezolid resistance in both staphylococci and enterococcal clinical strains is G2576T (Escherichia coli 23S rRNA gene numbering) (8,25,29). Another mutation (T2500A) was characterized in a single patient bloodstream isolate of MRSA (17).…”

mentioning

confidence: 99%

Clinical and Microbiological Aspects of Linezolid Resistance Mediated by the cfr Gene Encoding a 23S rRNA Methyltransferase

et al. 2008

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The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), the erm(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette mec type I. We were unable to detect the cfr gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the cfr gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of cfr-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method.

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“…2,3 Development of resistance in these reports was due to G2576T mutation in the 23S rRNA gene, and it appeared to be an uncommon finding. [2][3][4] However, the first outbreak of a linezolid-resistant MRSA due to a different resistance mechanism has recently been described: the acquisition of cfr gene, which also confers chloramphenicol, 16C macrolides, streptogramin A and clindamycin resistance. 5 Previously the cfr gene was described in other staphylococcal species of animal origin.…”

mentioning

confidence: 95%

Spread of cfr gene among staphylococci conferring resistance to linezolid in a patient under treatment

et al. 2011

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Linezolid resistance in a clinical isolate of Staphylococcus aureus

Cited by 924 publications

References 4 publications

In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp

In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp

Clinical and Microbiological Aspects of Linezolid Resistance Mediated by the cfr Gene Encoding a 23S rRNA Methyltransferase

Spread of cfr gene among staphylococci conferring resistance to linezolid in a patient under treatment

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