Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in Gram-negative bacteria: is it time for a paradigm shift?

Tuite, Nina; Reddington, Kate; Barry, Thomas; Zumla, Alimuddin; Enne, Virve I.

doi:10.1093/jac/dku083

Cited by 45 publications

(28 citation statements)

References 21 publications

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“…Patient outcome predictions derived from targeted sequence data of AMR genes may be imperfect owing to the multifactorial nature of drug resistance (Livermore & Wain, 2013;Tuite et al, 2014). The sources of resistance may be unknown, causing unexpected treatment failure, as AMR gene analysis may create false-positive or falsenegative results.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of infections with Gram-negative bacteria, the problem is daunting owing to the presence of hundreds of resistance genes and variants. Despite these potential obstacles, tests for AMR genes are in successful widespread clinical use today, with reported sensitivity and specificity of 72.3-100 and 55-100 %, respectively (Tuite et al, 2014). Olender (2013) reported 'very high' concordance between the phenotypic method (MIC determination) and the presence of the ermX gene for Corynebacterium isolated from the nasal mucosa, noting that this was the most common mechanism of resistance.…”

Section: G Bostwick and Othersmentioning

confidence: 99%

“…(Tuite et al, 2014). Resistance data from cultures have been available for decades, but provide no information regarding numerous abundant BV-associated bacteria that are difficult or impossible to culture, including many of the most abundant found only recently with advanced molecular diagnostics, such as Atopobium vaginae, Atopobium parvulum, Lactobacillus iners and other Lactobacillus spp., and multiple Lachnospiraceae spp.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women

Bostwick¹,

J²,

Hunt³

et al. 2016

Journal of Medical Microbiology

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Clinical management of bacterial vaginosis (BV) is difficult owing to inaccurate diagnostic tests, limited drug choices, and a high rate of recurrence. To our knowledge, there has not been a previous study of antimicrobial resistance (AMR) genes in community practice using nextgeneration sequencing (NGS). A case-control study (1 : 1 age-matched with and without BV) was undertaken in a series of 326 nongravid women of reproductive age with symptoms of BV to determine the prevalence of AMR genes. NGS was used to describe the complete vaginal microbiota and identify bacterial genes associated with resistance to: macrolides and/or lincosamides -ermA, ermB, ermC, erM, ermTR and mefA; tetracyclines, b-lactams, streptomycin, gentamicin and/or tobramycin -acrA, acrB, mecA, tet, tetA, tolC and aac2; 5-nitroimadazoles -nim and nimB; and triazoles -cdr1 and mdr1. An evidence base was created to inform treatment decisions applicable to individual patients. AMR genes were identified in all drug classes: macrolides, 35.2 %; lincosamides, 35.6 %; tetracyclines, 21.8 %; aminoglycosides (streptomycin, gentamicin and tobramycin), 5.2 % each; 5-nitroimidazoles, 0.3 %; and triazoles, 18.7 %. There was more than a fourfold-higher frequency of AMR genes in pathogens from BV than from non-BV patients for macrolides (58.2 versus 12.3 %, respectively), lincosamides (58.9 versus 12.3 %) and tetracyclines (35.6 versus 8.0 %) (Fisher's exact test; all p,0.001). For each patient with BV, the spectrum of resistance genes was matched to the pathogens present. AMR genes were present in the majority of vaginal microbiomes of patients with symptoms of BV.

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Section: Discussionmentioning

confidence: 99%

Section: G Bostwick and Othersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women

Bostwick¹,

J²,

Hunt³

et al. 2016

Journal of Medical Microbiology

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“…Several microarray platforms for carbapenemases have been developed, including Verigene, BioFire, and Check-Points. Sensitivities have been reported at 100% (41,42,43,44).…”

Section: Molecular Cp-cre Detection Methodsmentioning

confidence: 99%

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

2016

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The emergence and spread of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are a significant clinical and public health concern. Reliable detection of CP-CRE is the first step in combating this problem. There are both phenotypic and molecular methods available for CP-CRE detection. There is no single detection method that is ideal for all situations.G ram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospitalacquired infections, including urinary tract, bloodstream, and lower respiratory tract infections. These bacteria can acquire genes encoding multiple antibiotic resistance mechanisms, including extended-spectrum ␤-lactamases (ESBLs), AmpCs, and carbapenemases (1). ␤-Lactam drugs are often the primary therapeutic option for serious infections, and carbapenems in particular are often considered agents of last resort. Thus, the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) are a significant clinical and public health concern. CRE are often resistant to all ␤-lactam drugs and frequently carry mechanisms conferring resistance to other antimicrobial classes, further limiting treatment options. Although CRE infections are relatively infrequent, they have become more common in the United States since their emergence (2, 3, 4). Infections with these resistant bacteria are associated with higher mortality rates than those for infections caused by carbapenem-susceptible organisms (5).The epidemiologic description and phenotypic detection of CRE are complicated by the fact that Enterobacteriaceae may be nonsusceptible (intermediate or resistant) to carbapenems via a variety of mechanisms. Proteus, Providencia, and Morganella species demonstrate intrinsically elevated MICs to imipenem (6). Enterobacteriaceae can also produce ␤-lactamase enzymes such as AmpCs (chromosomal or acquired) and ESBLs that do not readily inactivate carbapenems on their own but can confer carbapenem resistance when combined with chromosomal porin mutations that prevent accumulation of ␤-lactam agents in the bacteria. Finally, the production of carbapenemase enzymes, typically found on mobile genetic elements, that inactivate carbapenem and other ␤-lactam antibiotics is increasingly common (1, 2). These carbapenemase-producing CRE (CP-CRE) frequently carry multiple resistance mechanisms, which can include redundant ␤-lactamases such as AmpCs and ESBLs and genes conferring resistance to other antimicrobial classes.Among the various types of CRE, CP-CRE have received the most attention because they have the greatest potential to contribute to the overall problem of antimicrobial resistance. Production of a carbapenemase usually confers resistance on its own, without requiring additional chromosomal mutations or accessory mechanisms. Because carbapenemase genes are carried on mobile genetic elements, these genes can be spread horizontally to naive bacteria, thus contributing to the reservoir of resistance in both environmental and clinical Enterob...

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“…With the ever increasing incidence of bacterial drug resistance, the need for rapid and reliable methods to predict antimicrobial susceptibility early in the course of treatment is ever more pressing (11). Advances in methodology and the decreasing cost of next-generation sequencing (NGS) have the potential to impact clinical microbiology ranging from species identification to antimicrobial susceptibility testing (12)(13)(14).…”

mentioning

confidence: 99%

The Resistome of Pseudomonas aeruginosa in Relationship to Phenotypic Susceptibility

Kos

Déraspe

McLaughlin

et al. 2015

Antimicrob Agents Chemother

231

267

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Many clinical isolates of Pseudomonas aeruginosa cause infections that are difficult to eradicate due to their resistance to a wide variety of antibiotics. Key genetic determinants of resistance were identified through genome sequences of 390 clinical isolates of P. aeruginosa, obtained from diverse geographic locations collected between 2003 and 2012 and were related to microbiological susceptibility data for meropenem, levofloxacin, and amikacin. ␤-Lactamases and integron cassette arrangements were enriched in the established multidrug-resistant lineages of sequence types ST111 (predominantly O12) and ST235 (O11). This study demonstrates the utility of next-generation sequencing (NGS) in defining relevant resistance elements and highlights the diversity of resistance determinants within P. aeruginosa. This information is valuable in furthering the design of diagnostics and therapeutics for the treatment of P. aeruginosa infections.

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Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in Gram-negative bacteria: is it time for a paradigm shift?

Cited by 45 publications

References 21 publications

Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women

Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

The Resistome of Pseudomonas aeruginosa in Relationship to Phenotypic Susceptibility

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