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Weekly Report Articles

26 September 2017

Gonococcal antibiotic surveillance in Scotland (GASS): prevalence, patterns and trends in 2016

Summary

  • The number of episodes of gonorrhoea submitted to SBSTIRL remained steady between 2015 and 2016. Around half of episodes were diagnosed by nucleic acid amplification only. The resistance surveillance in 2016 was therefore based on 50% of gonococcal infections in Scotland.
  • No resistance was observed to ceftriaxone, the recommended first-line therapy along with azithromycin, or to spectinomycin. No treatment failures were formally reported.
  • Decreased susceptibility to azithromycin has fallen to 0.9% of isolates. A small number of isolates (two) demonstrated high-level resistance to azithromycin.
  • The percentage of isolates resistant to cefixime has remained steady at 0.5%. The rate of resistance to ciprofloxacin has also remained steady (34.9%).
  • Continued surveillance for antibiotic resistance is essential for guiding the choice of effective therapeutic regimens for gonorrhoea and every effort should be made to maintain culture from a high proportion of gonococcal episodes of infection to avoid compromising the accuracy of surveillance data. This is particularly important in view of the outbreak of high-level azithromycin-resistant gonorrhoea seen in England.

Methodology

The Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) provides surveillance data on antimicrobial resistance for all gonococci isolated in Scotland. All cultured organisms are tested against seven antibiotics using the agar dilution method,1 and by E-tests (bioMérieux) when the minimum inhibitory concentration (MIC) exceeds the dilution series. Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST)2 is performed on a proportion isolates and specimens positive by N. gonorrhoeae nucleic acid amplification tests (NAAT) submitted to SBSTIRL where a culture is not available.

Episodes of gonorrhoea in Scotland

The number of episodes of gonorrhoea is obtained by the manual removal from the database of duplicate samples from the same patient taken within a six-week period, and presumed duplicate patients who appear to have been tested both in primary care and at sexual health services. A total of 2193 episodes of gonococcal infection were reported by SBSTIRL in 2016. Of these, 17 were cultures non-recoverable on receipt in the laboratory and 1092 were diagnosed by NAAT with no culture available. Antibiotic susceptibility testing was therefore performed on isolates from 1087 episodes (50%). Since April 2015, NG-MAST has only been performed on a proportion of samples, NG-MAST data being available for 727 episodes (33%). NG-MAST data can be a useful predictor of antibiotic susceptibility profile for those sequence types (STs) that occur commonly and for which no cultured isolate exists.3

Table 1 shows gonorrhoea episodes and trends by gender. Total gonorrhoea episodes show no change in comparison with 2015. Males accounted for 76.0% of episodes in 2016. As has been the case for every year for which such data have been available, a larger proportion (51.5%) of diagnoses in women were by NAAT only, compared with 49.2% in men and 49.8% overall.

General antibiotic susceptibility trends

Table 2 and Figure 1 provide resistance trends for the antibiotics tested over the last five years and Table 3 gives the pattern of resistance for isolates in 2016.

In total, 461 (42.4%) of the 1087 episodes for which susceptibility data were available exhibited decreased susceptibility to one or more antibiotics tested, down from the 50.1% seen in 2015. There were no isolates with decreased susceptibility to ceftriaxone or resistance to spectinomycin in 2016.

This GASS report continues to report with the same antibiotic breakpoints used in previous years, although SBSTIRL now use EUCAST (European Committee on Antimicrobial Susceptibility Testing) v7.1 breakpoints to report antibiotic susceptibility.4

Cephalosporin resistance

Resistance to cefixime (MIC >0.125 mg/L) was found in two isolates in 2015 (0.2%), similar to previous years. In 2016 five isolates (0.5%) were cefixime-resistant. All isolates remained susceptible to ceftriaxone.

Azithromycin decreased susceptibility

Decreased susceptibility to azithromycin exceeded 5% in 2007 (44 of 845 episodes, 5.2%), reduced by 2009 to 1.6% (11 episodes), and fell gradually to a low of 0.5% in 2013. In 2015 Public Health England (PHE) reported an outbreak of high-level azithromycin resistance (HiL-AziR; MIC >256 mg/l).5 SBSTIRL detected 10 isolates with decreased susceptility to azithromycin (0.9%), down from 2015 (2.4%), with two being HiL-AziR.

Penicillin and tetracycline resistance

Overall resistance to penicillin and tetracycline (plasmid and chromosomal) was found in 8.6% and 23.4% of culture episodes respectively. Penicillin resistance, both chromosome- and plasmid-mediated, has decreased considerably this year.

Ciprofloxacin resistance

Ciprofloxacin resistance (MIC ≥ 1mg/l) has remained steady in comparison with 2015, with 351 of 1087 episodes (32.3%) resistant. Prior to 2015, the percentage of isolates demonstrating resistance to ciprofloxacin was declining.

Sequence type and antibiotic resistance

NG-MAST is a highly discriminatory typing scheme that differentiates between isolates on the basis of the sequence variation observed in two genes, coding for the por protein and transferrin binding protein b (tbpb). Each sequence type (ST) is unique and differs from any other by at least one nucleotide. Clusters of isolates sharing the same ST can be observed and both phenotypic and demographic data support the validity of the clusters as containing related isolates. Sequence types represented by five or more antibiotic resistant episodes are given in Table 4, plus STs associated with azithromycin and cefixime resistance.

Plasmid-mediated resistance has previously been associated with infection outside the UK6 and limited onward transmission in Scotland. However, in 2016 as seen in previous years, PPNG and TRNG appeared to be associated with multiple isolations of the same ST, giving a likely indication of clusters of infection.

A number of STs were associated with more than one resistance category. ST 11690 is associated with ciprofloxacin resistance, with some isolates also showing chromosomally-mediated tetracycline resistance. It has previously been associated with an elevated cefixime MIC (0.12 mg/l) and in 2016 three isolates were resistant. The 2014 data indicated that ST 1407 was associated with cefixime resistance in around a third of isolates. In 2016, none of the five isolates were cefixime-resistant, although all had elevated MICs of 0.12 (mg/l).

Acknowledgements

I would like to acknowledge all microbiologists who have submitted isolates and specimens to SBSTIRL throughout the year, and all sexual health clinicians for their support. Thanks are also due to staff at SBSTIRL for performing susceptibility testing and NG-MAST typing and particularly to Anne-Marie Logue for maintaining the SBSTIRL databases.

References

  1. Young H, Moyes A, Robertson DHH et al. Gonococcal infection within Scotland: antigenic heterogeneity and antibiotic susceptibility of infecting strains. European Journal of Epidemiology. 1990;6:1-8.
  2. Martin IMC, Ison CA, Aanensen DM et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. Journal of Infectious Diseases. 2004;189:1497-1505. Available from: https://academic.oup.com/jid/article/189/8/1497/821449/Rapid-Sequence-Based-Identification-of-Gonococcal. (accessed 21 September 2017).
  3. Palmer HM, Young H, Graham C, Dave J. Prediction of antibiotic resistance using Neisseria gonorrhoeae multi-antigen sequence typing. Sexually Transmitted Infections. 2008;84(4):280-4. Available from: http://sti.bmj.com/content/84/4/280. (accessed 21 September 2017).
  4. European Committee on Antimicrobial Susceptibility Testing. Clinical breakpoints. Available from: http://www.eucast.org/clinical_breakpoints/. (accessed 21 September 2017)
  5. Public Health England. Outbreak of high-level azithromycin resistant gonorrhoea in England: an update. Health Protection Report. 2016;10(30). Available from: https://www.gov.uk/government/publications/high-level-azithromycin-resistant-gonorrhoea-in-england. (accessed 21 September 2017).
  6. Young H, Moyes A, Noone A. Epidemiology and treatment outcome of infection with antibiotic resistant strains of Neisseria gonorrhoeae in Scotland. Communicable Disease and Public Health. 1999;2(3):198-202. Available from: http://webarchive.nationalarchives.gov.uk/20121103032255/http://www.hpa.org.uk/cdph/issues/CDPHVol2/no3/CDPHv2n3.htm. (accessed 21 September 2017).
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Author(s): Prepared by: Jill Shepherd Vol: 51 No: 38 Year: 2017 Page:

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