An outbreak of high-level azithromycin resistant<i>Neisseria gonorrhoeae</i>in England

Chisholm, Stephanie; Wilson, Janet; Alexander, Sarah; Tripodo, Francesco; Al‐Shahib, Ali; Schaefer, Ulf; Lythgow, Kieren; Fifer, Helen

doi:10.1136/sextrans-2015-052312

Cited by 88 publications

(86 citation statements)

References 9 publications

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“…In our population azithromycin resistance has not been above 1.5% since 2012, which is lower than the overall European prevalence. Although both the mean MIC and the percentage of resistance have increased slightly during our study period, the high increase reported elsewhere in Europe, was not seen in our population [9,20]. The outbreak of azithromycin high-resistant isolates in England in 2015 occurred despite the use of dual therapy, as recommended by European and United States Centers for Disease Control and Prevention (CDC) guidelines [4,5].…”

Section: Discussionmentioning

confidence: 63%

“…Taking the historical course of emerging antimicrobial-resistant gonorrhoea strains into account, without additional measures, a further decrease in ceftriaxone and azithromycin susceptibility is to be expected [1]. Moreover, high level azithromycin-resistant gonorrhoea has been reported in the United Kingdom (UK) since 2015 [9]. In addition, the first treatment failure on dual therapy of azithromycin and ceftriaxone was reported in 2016 [14].…”

Section: Introductionmentioning

confidence: 99%

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Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

et al. 2017

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Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

et al. 2017

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“…Likewise, the limited clonal spread as compared to ESC RS and quinolone resistance (Figure 1), as well as the inferred frequent return to susceptibility, implies that azithromycin resistance often incurs significant fitness costs. However, recent reports of an outbreak of azithromycin-resistant gonorrhea in England [27] and an increase in azithromycin resistance in the United States [8] raise concern that these fitness costs may be mitigated in some genomic backgrounds.…”

Section: Discussionmentioning

confidence: 99%

Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000–2013

et al. 2016

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Background. Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms.Methods. We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project.Results. Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread.Conclusions. Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea.

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“…Chromosomal mutations mediating low‐level resistance to beta‐lactams and tetracycline are common in N. gonorrhoeae isolates, and they are widespread across the phylogeny . While azithromycin resistance is less common than resistance to previously used drugs, resistance or reduced susceptibility has arisen across a large number of genomic backgrounds . In contrast, reduced susceptibility to ESCs (ESC‐RS) is primarily clonal, and the majority of ESC‐RS isolates belong to only a few major lineages .…”

Section: From Pathogen To Superbug: Treatment and Resistancementioning

confidence: 99%

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

Mortimer

Grad

2018

Annals of the New York Academy of Sciences

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Infections with Neisseria gonorrhoeae, a sexually transmitted pathogen that causes urethritis, cervicitis, and more severe complications, are increasing. Gonorrhea is typically treated with antibiotics; however, N. gonorrhoeae has rapidly acquired resistance to many antibiotic classes, and lineages with reduced susceptibility to the currently recommended therapies are emerging worldwide. In this review, we discuss the contributions of whole genome sequencing (WGS) to our understanding of resistant N. gonorrhoeae. Genomics has illuminated the evolutionary origins and population structure of N. gonorrhoeae and the magnitude of horizontal gene transfer within and between Neisseria species. WGS can be used to predict the susceptibility of N. gonorrhoeae based on known resistance determinants, track the spread of these determinants throughout the N. gonorrhoeae population, and identify novel loci contributing to resistance. WGS has also allowed more detailed epidemiological analysis of transmission of N. gonorrhoeae between individuals and populations than previously used typing methods. Ongoing N. gonorrhoeae genomics will complement other laboratory techniques to understand the biology and evolution of the pathogen, improve diagnostics and treatment in the clinic, and inform public health policies to limit the impact of antibiotic resistance.

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An outbreak of high-level azithromycin resistantNeisseria gonorrhoeaein England

Cited by 88 publications

References 9 publications

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000–2013

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

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