Tigecycline: an update

Stein, Gary E.; Babinchak, Timothy

doi:10.1016/j.diagmicrobio.2012.12.004

Cited by 167 publications

(141 citation statements)

References 57 publications

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“…In contrast, TIG resistance remains seldom reported in Gram-positive bacteria, even if some intermediate or resistant strains have been described in Staphylococcus spp. and Enterococcus spp., but it has never been detected in E. faecium (8,(10)(11)(12)23). The first clinical isolate of E. faecalis resistant to TIG (MIC, 1 g/ml) was found in 2008 (11).…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

Cattoir

Isnard

Cosquer

et al. 2015

Antimicrob Agents Chemother

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c Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in Enterococcus faecium. Using the serial passage method, in vitro mutant AusTig and in vitro mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 g/ml) were obtained from strains E. faecium Aus0004 and HM1070 (MICs, 0.03 g/ml), respectively. In addition, two vancomycin-resistant E. faecium clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 g/ml, respectively) were studied. Compared to the wild-type strains, the in vitro mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the rpsJ gene (efau004_00094, coding for the S10 protein of the 30S ribosomal subunit), efau004_01228 (encoding a cation transporter), efau004_01636 (coding for a hypothetical protein), and efau004_02455 (encoding the L-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein.In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci.

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Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

Cattoir

Isnard

Cosquer

et al. 2015

Antimicrob Agents Chemother

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“…Tigecycline is a structural analog of tetracycline, and is mostly used as a broad‐spectrum antibiotic against gram‐positive and gram‐negative pathogens 9, 10, 11. Currently, it is approved for the treatment of adults with complicated intraabdominal, skin, soft tissue and skin structure infections, and community‐acquired bacterial pneumonia 9, 12.…”

Section: Introductionmentioning

confidence: 99%

A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia

et al. 2016

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Acute myeloid leukemia (AML) cells meet the higher energy, metabolic, and signaling demands of the cell by increasing mitochondrial biogenesis and mitochondrial protein translation. Blocking mitochondrial protein synthesis through genetic and chemical approaches kills human AML cells at all stages of development in vitro and in vivo. Tigecycline is an antimicrobial that we found inhibits mitochondrial protein synthesis in AML cells. Therefore, we conducted a phase 1 dose‐escalation study of tigecycline administered intravenously daily 5 of 7 days for 2 weeks to patients with AML. A total of 27 adult patients with relapsed and refractory AML were enrolled in this study with 42 cycles being administered over seven dose levels (50–350 mg/day). Two patients experienced DLTs related to tigecycline at the 350 mg/day level resulting in a maximal tolerated dose of tigecycline of 300 mg as a once daily infusion. Pharmacokinetic experiments showed that tigecycline had a markedly shorter half‐life in these patients than reported for noncancer patients. No significant pharmacodynamic changes or clinical responses were observed. Thus, we have defined the safety of once daily tigecycline in patients with refractory AML. Future studies should focus on schedules of the drug that permit more sustained target inhibition.

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“…The drug binds to bacterial ribosomes with high affinity and therefore evades the major resistance mechanisms of tetracycline, retaining activity against a broad range of both Gram-positive and Gramnegative bacteria (4,6), including multidrug-resistant isolates. However, tigecycline resistance has emerged recently and been detected during treatment with this agent (7)(8)(9)(10).…”

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confidence: 99%

Molecular Epidemiology and Mechanisms of Tigecycline Resistance in Clinical Isolates of Acinetobacter baumannii from a Chinese University Hospital

Deng

Zhu

et al. 2014

Antimicrob Agents Chemother

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bBecause of its remarkable ability to acquire antibiotic resistance and to survive in nosocomial environments, Acinetobacter baumannii has become a significant nosocomial infectious agent worldwide. Tigecycline is one of the few therapeutic options for treating infections caused by A. baumannii isolates. However, tigecycline resistance has increasingly been reported. Our aim was to assess the prevalence and characteristics of efflux-based tigecycline resistance in clinical isolates of A. baumannii collected from a hospital in China. A total of 74 A. baumannii isolates, including 64 tigecycline-nonsusceptible A. baumannii (TNAB) and 10 tigecycline-susceptible A. baumannii (TSAB) isolates, were analyzed. The majority of them were determined to be positive for adeABC, adeRS, adeIJK, and abeM, while the adeE gene was found in only one TSAB isolate. Compared with the levels in TSAB isolates, the mean expression levels of adeB, adeJ, adeG, and abeM in TNAB isolates were observed to increase 29-, 3-, 0.7-, and 1-fold, respectively. The efflux pump inhibitors (EPIs) phenyl-arginine-␤-naphthylamide (PA␤N) and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) could partially reverse the resistance pattern of tigecycline. Moreover, the tetX1 gene was detected in 12 (18.8%) TNAB isolates. To our knowledge, this is the first report of the tetX1 gene being detected in A. baumannii isolates. ST208 and ST191, which both clustered into clonal complex 92 (CC92), were the predominant sequence types (STs). This study showed that the active efflux pump AdeABC appeared to play important roles in the tigecycline resistance of A. baumannii. The dissemination of TNAB isolates in our hospital is attributable mainly to the spread of CC92.

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Tigecycline: an update

Cited by 167 publications

References 57 publications

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia

Molecular Epidemiology and Mechanisms of Tigecycline Resistance in Clinical Isolates of Acinetobacter baumannii from a Chinese University Hospital

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