Tigecycline activity: low resistance rates but problematic disc breakpoints revealed by a multicentre sentinel survey in the UK

Hope, Russell; Mushtaq, Shazad; James, Deborah; Pllana, Teresa; Warner, Marina; Livermore, David M.; Brown, D L; Rooney, Paul J.; Palmer, Richard; Croal, J.; Weinbren, M.; Hogue, Susan; Gould, Katherine A.; Cumberland, Nigel; Logan, M. N.; Pillay, D.; Thomas, Chang-Yao Tsao; Want, S.; Oppenheim, Beryl; Kent, Robert A.; Manjula,; Rizkalla, None; Wade, Jim; Wilcox, Mark H.; Swann, A.; Leonard, Anne; Galloway,; Al-Wali, Walid; Hudson, S. J.; Rogers, James E.; Winstanley, T. G.; Riley, Unell; Johnstone, D; El-Bouri, Khalid; Jones, G.; MacGowan, A. P.; Jepson, Annette; Unsworth, None; James, E. O.; Shetty, Nandini; Shemko, M.; Hastings, Mark; Lafong, Cyril; Richards, Shawn; Nash, James; Waghorn, David; Cullen, Martin E.; Todd, Neil; Anderson, A. Nixon; D’Arcy, S.; Goodburn, C.; Bignardi, G.

doi:10.1093/jac/dkq370

Cited by 18 publications

(16 citation statements)

References 15 publications

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“…Clinical labs using disc diffusion on a daily basis could properly categorize true tigecycline susceptible and resistant strains by using a zone breakpoint of susceptible ≥ 21 mm and resistant ≤ 16 mm (VME and MaE 0%) (Mueller-Hinton agar from Difco, BD, New Jersey, US). Strains with halos between 17-20 mm could fall in any of the three MIC categories, although most of the isolates had a trend toward susceptibility by the reference (MIC) method, as has been also observed in other study using the BSAC method [12]. We observed in this series that 40% of strains with intermediate halos showed susceptibility by MIC, and only 7% resulted true resistant.…”

Section: Resultssupporting

confidence: 84%

“…The strains were submitted to the National Reference Laboratory because they either had an XDR phenotype (50% of the isolates) or required a tigecycline/fosfomycin MIC confirmation. The resistant mechanisms were characterized by PCR and DNA sequencing and included (n): KPC (70), CTX-M-2 plus porin loss (21), OXA-163 (3), IMP-8 (3), VIM-2 (2), VIM-1 (1), NDM-1 (1), OXA-48-like (1), ESBLs (CTXM-2, PER-2, SHV-2, SHV-5, SHV-18) (76), narrow-spectrum beta-lactamases (6), and wild type isolates (including ATCC quality control strains) (12). The isolates were from clinical sources and they were single isolates from each patient.…”

Section: Methodsmentioning

confidence: 99%

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Tigecycline and intravenous fosfomycin zone breakpoints equivalent to the EUCAST MIC criteria for Enterobacteriaceae

Pasterán

Lucero

Rapoport

et al. 2012

J Infect Dev Ctries

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Introduction: Tigecycline and intravenous (i.v.) fosfomycin could be alternative therapeutic options for the treatment of carbapenemasepossessing Enterobacteriaceae bacterial infections. However, routine laboratories are forced to test these drugs using minimum inhibitory concentration (MIC) methods as zone breakpoints are not available for the disc diffusion technique. Methodology: Clinical and Laboratory Standards Institute methods for agar dilution and disc diffusion were compared to determine tentative zone breakpoints that best correlate to tigecycline and i.v. fosfomycin MIC breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing. A total of 195 Enterobacteriaceae with defined mechanisms of resistance were tested in duplicate assays. Half of the strains were characterized as carbapenemase producers (KPC-2, OXA-48, OXA-163, VIM-1, VIM-2, IMP-8, NDM-1). Results: Corresponding zone diameters of susceptible ≥15mm, resistant ≤12mm and susceptible ≥17mm, resistant ≤15mm for the 50µg fosfomycin plus 50μg glucose-6-phosphate and 200μg fosfomycin plus 50μg glucose-6-phosphate discs, respectively, allowed categorization of the strains with an acceptable level of error (< 10% minor errors, < 1.5 % major errors, < 1% very major errors and categorical agreement > 90%). For the 15µg tigecycline disc, the best performance was achieved with the corresponding zone diameters of susceptible ≥21mm and resistant ≤16mm, which eliminated the very major and major errors but not the minor errors (34.4%). Conclusions: Based on these results, tigecycline and fosfomycin can be included in the routine panel of antibiotics for susceptibility testing by disc diffusion to provide fast and reliable information for the selection of treatment alternatives, especially for strains with extreme resistance, as carbapenemase producers.

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Section: Resultssupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Tigecycline and intravenous fosfomycin zone breakpoints equivalent to the EUCAST MIC criteria for Enterobacteriaceae

Pasterán

Lucero

Rapoport

et al. 2012

J Infect Dev Ctries

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“…The interchangeability of tigecycline susceptibility results of CR Enterobacteriaceae and A. baumannii is not well defined (13). Previous studies have reported discrepant Etest and BMD results with tigecycline, mainly for A. baumannii (3,7,10,12,14,19,22). Scarce data are available on the accuracy of VItek2 with MDR pathogens (15).…”

Section: Susceptibility Testing Methodsmentioning

confidence: 99%

“…It has been previously noted that discrepancies may exist when different methods are used (3,7,14,19,22). It was also reported that disk diffusion and Etest have a poor correlation with BMD, especially for A. baumannii (3,10,12,22). Furthermore, the accuracy of the Vitek2 automated system (bioMérieux, Marcy l' Etoile, France) has not been adequately evaluated for tigecycline (15).…”

mentioning

confidence: 99%

Comparative Evaluation of Tigecycline Susceptibility Testing Methods for Expanded-Spectrum Cephalosporin- and Carbapenem-Resistant Gram-Negative Pathogens

et al. 2012

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We evaluated the Vitek2, Etest, and MIC Test Strip (MTS) methods of tigecycline susceptibility testing with 241 expanded-spectrum cephalosporin-resistant and/or carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii clinical isolates by using dry-form broth microdilution (BMD) as the reference method. The MIC 50/90 s were as follows: BMD, 1/4 g/ml; Vitek2, 4/>8 g/ml; Etest, 2/4 g/ml; MTS, 0.5/2 g/ml. Vitek2 produced 9.1/21.2% major errors, Etest produced 0.4/0.8% major errors, and MTS produced no major errors but 0.4/3.3% very major errors (FDA/EUCAST breakpoints). Vitek2 tigecycline results require confirmation by BMD or Etest for multidrug-resistant pathogens. Carbapenem resistance has steadily increased in several regions, representing the most significant resistance issue among multidrug-resistant (MDR) Gram-negative pathogens (2, 17, 18). Tigecycline and colistin are among the few antimicrobials active and are commonly used for infections caused by carbapenem-resistant (CR) Enterobacteriaceae and Acinetobacter baumannii (2,4,16,21).The increasing clinical use of tigecycline necessitates rapid, simple, and accurate susceptibility testing methods. Several methods have been evaluated for routine tigecycline susceptibility testing (1,12,14,19,22) with broth microdilution (BMD) as the reference method. It has been previously noted that discrepancies may exist when different methods are used (3,7,14,19,22). It was also reported that disk diffusion and Etest have a poor correlation with BMD, especially for A. baumannii (3,10,12,22). Furthermore, the accuracy of the Vitek2 automated system (bioMérieux, Marcy l' Etoile, France) has not been adequately evaluated for tigecycline (15).In this study, we evaluated three routine tigecycline susceptibility methods, Vitek2, Etest (bioMérieux), and MIC Test Strip (MTS; Liofilchem SRL, Roseto degli Abruzzi, Italy) in comparison with BMD. These methods were applied to a large collection of CR Enterobacteriaceae and A. baumannii and expanded-spectrum cephalosporin-resistant (ESCR) Enterobacteriaceae isolates.Bacterial isolates. This study included 241 clinical isolates recovered during 2008 to 2011 from patients in five tertiary-care hospitals located in different regions of Greece, consisting of CR (K. pneumoniae carbapenemase [KPC]-producing K. pneumoniae, n ϭ 73; VIM-producing K. pneumoniae, n ϭ 39; KPCand VIM-producing K. pneumoniae, n ϭ 13; OXA-58-producing A. baumannii, n ϭ 56) and ESCR isolates (extended-spectrum ␤-lactamase [ESBL]-producing Escherichia coli, n ϭ 20; ESBLproducing K. pneumoniae, n ϭ 20; Enterobacter spp., n ϭ 20). Identification was performed with Vitek2. Phenotypic carbapenemase detection was performed as described previously (23). Common broad-spectrum ␤-lactamase genes (for KPC, OXA-48, OXA-58, metallo-␤-lactamases, and ESBLs) were sought by PCR (20). Susceptibility testing methods.The FDA-cleared commercial dry-form microtiter panels and cation-adjusted Mueller-Hinton broth with N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (Sen...

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“…Tigecycline is a member of the glycylcycline group of antibiotics, and was registered in the EU in April 2006 [18]. This bacteriostatic antibiotic acts as a protein synthesis inhibitor by binding to the 30S ribosomal subunit [19].…”

Section: Introductionmentioning

confidence: 99%

Tigecycline challenge triggers sRNA production in Salmonella enterica serovar Typhimurium

Schneiders

2012

BMC Microbiol

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BackgroundBacteria employ complex transcriptional networks involving multiple genes in response to stress, which is not limited to gene and protein networks but now includes small RNAs (sRNAs). These regulatory RNA molecules are increasingly shown to be able to initiate regulatory cascades and modulate the expression of multiple genes that are involved in or required for survival under environmental challenge. Despite mounting evidence for the importance of sRNAs in stress response, their role upon antibiotic exposure remains unknown. In this study, we sought to determine firstly, whether differential expression of sRNAs occurs upon antibiotic exposure and secondly, whether these sRNAs could be attributed to microbial tolerance to antibiotics.ResultsA small scale sRNA cloning strategy of Salmonella enterica serovar Typhimurium SL1344 challenged with half the minimal inhibitory concentration of tigecycline identified four sRNAs (sYJ5, sYJ20, sYJ75 and sYJ118) which were reproducibly upregulated in the presence of either tigecycline or tetracycline. The coding sequences of the four sRNAs were found to be conserved across a number of species. Genome analysis found that sYJ5 and sYJ118 mapped between the 16S and 23S rRNA encoding genes. sYJ20 (also known as SroA) is encoded upstream of the tbpAyabKyabJ operon and is classed as a riboswitch, whilst its role in antibiotic stress-response appears independent of its riboswitch function. sYJ75 is encoded between genes that are involved in enterobactin transport and metabolism. Additionally we find that the genetic deletion of sYJ20 rendered a reduced viability phenotype in the presence of tigecycline, which was recovered when complemented. The upregulation of some of these sRNAs were also observed when S. Typhimurium was challenged by ampicillin (sYJ5, 75 and 118); or when Klebsiella pneumoniae was challenged by tigecycline (sYJ20 and 118).ConclusionsSmall RNAs are overexpressed as a result of antibiotic exposure in S. Typhimurium where the same molecules are upregulated in a related species or after exposure to different antibiotics. sYJ20, a riboswitch, appears to possess a trans-regulatory sRNA role in antibiotic tolerance. These findings imply that the sRNA mediated response is a component of the bacterial response to antibiotic challenge.

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Tigecycline activity: low resistance rates but problematic disc breakpoints revealed by a multicentre sentinel survey in the UK

Cited by 18 publications

References 15 publications

Tigecycline and intravenous fosfomycin zone breakpoints equivalent to the EUCAST MIC criteria for Enterobacteriaceae

Tigecycline and intravenous fosfomycin zone breakpoints equivalent to the EUCAST MIC criteria for Enterobacteriaceae

Comparative Evaluation of Tigecycline Susceptibility Testing Methods for Expanded-Spectrum Cephalosporin- and Carbapenem-Resistant Gram-Negative Pathogens

Tigecycline challenge triggers sRNA production in Salmonella enterica serovar Typhimurium

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