Breakthrough bacteraemia with a susceptible Enterococcus faecalis during tigecycline monotherapy

Parsonage, M.; Shah, S.I.; Moss, Peter; Thaker, Hiten; Meigh, R.; Balaji, Ariyur; Elston, James; Barlow, Gavin

doi:10.1093/jac/dkp455

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…However, fully resistant Klebsiella strains have been described previously (6,28), suggesting that several mechanisms might contribute to tigecycline resistance. Acquisition of mutations in ramR may represent one step in the development of full resistance; however, in certain body compartments like the bloodstream, where only low concentrations of tigecycline can be achieved, an intermediate phenotype may be sufficient to result in therapeutic failure of tigecycline (3,18). Other resistance mechanisms, like Tn1721-associated tet(A) (9,31), may be additive and upon acquisition successively result in full resistance.…”

mentioning

confidence: 99%

ramR Mutations in Clinical Isolates of Klebsiella pneumoniae with Reduced Susceptibility to Tigecycline

Hentschke

Wolters

Sobottka

et al. 2010

Antimicrob Agents Chemother

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Five Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline (MIC, 2 g/ml) were analyzed. A gene homologous to ramR of Salmonella enterica was identified in Klebsiella pneumoniae. Sequencing of ramR in the nonsusceptible Klebsiella strains revealed deletions, insertions, and point mutations. Transformation of mutants with wild-type ramR genes, but not with mutant ramR genes, restored susceptibility to tigecycline and repressed overexpression of ramA and acrB. Thus, this study reveals a molecular mechanism for tigecycline resistance in Klebsiella pneumoniae.

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confidence: 99%

ramR Mutations in Clinical Isolates of Klebsiella pneumoniae with Reduced Susceptibility to Tigecycline

Hentschke

Wolters

Sobottka

et al. 2010

Antimicrob Agents Chemother

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“…Regarding bacteremia, a recent review article reported 114 patients with all-cause bacteremia treated with tigecycline, of whom 78 were given monotherapy [74]. Among them, 16 cases with A. baumannii and 16 due to Enterobacteriaceae were included, 8 (25%) of whom died because they failed therapy.…”

Section: Clinical Implications Of Pk/pd Of Tigecyclinementioning

confidence: 99%

Pharmacokinetic and pharmacodynamic evaluation of tigecycline

Giamarellou

Poulakou

2011

Expert Opinion on Drug Metabolism & Toxicology

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Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.

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Bacterial Infections

Leather¹,

Wingard²

2015

Thomas’ Hematopoietic Cell Transplantation

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Breakthrough bacteraemia with a susceptible Enterococcus faecalis during tigecycline monotherapy

Cited by 6 publications

References 16 publications

ramR Mutations in Clinical Isolates of Klebsiella pneumoniae with Reduced Susceptibility to Tigecycline

ramR Mutations in Clinical Isolates of Klebsiella pneumoniae with Reduced Susceptibility to Tigecycline

Pharmacokinetic and pharmacodynamic evaluation of tigecycline

Bacterial Infections

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