Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018

Eyre, David W; Town, Katy; Street, Teresa; Barker, Leanne; Sanderson, Nicholas D.; Cole, Michelle; Mohammed, Hamish; Pitt, Rachel; Gobin, Maya; Irish, Charles; Gardiner, Daniel; Sedgwick, James; Beck, Charles R.; Saunders, John; Turbitt, Deborah; Cook, Clare; Phin, Nick; Nathan, Bavithra; Horner, Patrick J; Fifer, Helen

doi:10.2807/1560-7917.es.2019.24.10.1900147

Cited by 117 publications

(102 citation statements)

References 22 publications

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“…Further, infections might be cleared even in the case of undetected resistance, and multi-drug therapy may similarly mask novel resistance to individual drugs. For example, one of the first identified cases of infection with N. gonorrhoeae with ceftriaxone resistance and intermediate azithromycin resistance in the UK was identified as NAAT-negative two weeks after treatment with ceftriaxone and azithromycin ( 14 ). Thus, while continued collection of clinical outcome data is crucial to defining the relationship between phenotypic susceptibility test results and expected treatment outcome, surveillance programs designed to regularly sample a sufficient fraction of isolates in a given population, incorporating relevant epidemiological information, may represent the most reliable strategy for comprehensive detection of novel resistance variants.…”

Section: Additional Considerations For Implementationmentioning

confidence: 99%

Quantifying the surveillance required to sustain genetic marker-based antibiotic resistance diagnostics

Hicks

Kissler

Lipsitch

et al. 2019

Preprint

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Diagnostics that minimize the time to selection of an appropriate antibiotic treatment represent an important strategy in addressing the challenge of antimicrobial resistance (AMR). Among this class of diagnostics, the use of pathogen genotype to predict AMR phenotype has been facilitated by advances in rapid sequencing platforms. A longstanding objection to this approach, however, is that the emergence of novel resistance mechanisms will inevitably lead to a decline in the sensitivity of these diagnostics. Here, we show that while the sensitivities of some genetic markers of resistance remain stably high, sensitivities of other markers rapidly decline, as expected, due to the emergence of novel resistance variants. We then present a simple mathematical framework that defines the sampling and phenotypic testing rates needed for early detection of novel resistance variants and thus demonstrate how surveillance can help maintain the sensitivity and utility of sequence-based AMR diagnostics.One sentence summaryTargeted sampling strategies are necessary for early detection of novel resistance mechanisms and sustainability of genotype-based detection of novel resistance mechanisms and sustainability of genotype-based diagnostics.

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Section: Additional Considerations For Implementationmentioning

confidence: 99%

Quantifying the surveillance required to sustain genetic marker-based antibiotic resistance diagnostics

Hicks

Kissler

Lipsitch

et al. 2019

Preprint

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“…Further, the requirement of confirmatory phenotyping to identify novel resistance may not extend to pathogens that are expected to be associated with reliably-identifiable treatment failures, as for these pathogens, identification of treatment failure likely represents the most efficient method of novel resistance variant detection 61 . However, for other pathogens, such as N. gonorrhoeae 62 , treatment failures may go undetected for reasons including partial abatement of symptoms or long treatment regimens. Ultimately, as genotype-based diagnostics for antibiotic resistance become available for more species, it will be important to assess the efficiencies of these approaches across pathogens with different clinical, epidemiological, and evolutionary paradigms.…”

Section: Discussionmentioning

confidence: 99%

Targeted surveillance strategies for efficient detection of novel antibiotic resistance variants

Hicks

Kissler

Mortimer

et al. 2020

Preprint

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20Genotype-based diagnostics for antibiotic resistance represent a promising alternative to 21 empiric therapy, reducing inappropriate and ineffective antibiotic use. However, because 22 103 Results: 104Composition of the datasets. 105The datasets (Table 1) were biased across patient demographics and/or geographic 106 regions (Tables S1 and S2). Isolates from men and men who have sex with men (MSM) 107 were overrepresented in datasets 1 and 2 compared to overall gonorrhea incidence in 108 men and MSM in the US and Australia, respectively, during the study periods (Table S2, 109 P < 0.001 for both datasets by chi-squared test of men vs. women and MSM vs. non-110 MSM in dataset vs. reported incidence). Dataset 4 was comprised exclusively of isolates 111 from men 31 . While it is difficult to estimate the prevalence of pharyngeal gonococcal 112 infections, as they tend to be asymptomatic 32 , pharyngeal isolates represented 4% and 113

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“…ONT data were compared with Illumina data available for the reference strains and clinical isolates, which was used as a gold standard together with published descriptions of the variants present. 10,12,13 Illumina data were processed as described previously. 14 Table 1.…”

Section: Data Sourcesmentioning

confidence: 99%

“…More details on the specific resistance variants can be found in. 10,12,13 In addition, we also tested our final algorithm on 10 nanopore metagenomic sequences from N. gonorrhoeae positive urine samples obtained from men with symptomatic urethral gonorrhoea, described previously. 2 Cultured isolates from the same infections were sequenced with an Illumina MiniSeq, following the manufacturer's instructions, to allow for comparisons.…”

Section: Data Sourcesmentioning

confidence: 99%

High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic Nanopore sequencing

Sanderson

Swann

Barker

et al. 2020

Preprint

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The rise of antimicrobial resistant Neisseria gonorrhoeae is a significant public health concern. Against this background, rapid culture-independent diagnostics may allow targeted treatment and prevent onward transmission. We have previously shown metagenomic sequencing of urine samples from men with urethral gonorrhoea can recover near-complete N. gonorrhoeae genomes. However, disentangling the N. gonorrhoeae genome from metagenomic samples and robustly identifying antimicrobial resistance determinants from error-prone Nanopore sequencing is a substantial bioinformatics challenge.Here we demonstrate an N. gonorrhoeae diagnostic workflow for analysis of metagenomic sequencing data obtained from clinical samples using R9.4.1 Nanopore sequencing. We compared results from simulated and clinical infections with data from known reference strains and Illumina sequencing of isolates cultured from the same patients. We evaluated three Nanopore variant callers and developed a random forest classifier to filter called SNPs. Clair was the most suitable variant caller after SNP filtering. A minimum depth of 20x reads was required to confidently identify resistant determinants over the entire genome. Our findings show that metagenomic Nanopore sequencing can provide reliable diagnostic information in N. gonorrhoeae infection.

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Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018

Cited by 117 publications

References 22 publications

Quantifying the surveillance required to sustain genetic marker-based antibiotic resistance diagnostics

Quantifying the surveillance required to sustain genetic marker-based antibiotic resistance diagnostics

Targeted surveillance strategies for efficient detection of novel antibiotic resistance variants

High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic Nanopore sequencing

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