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Abstract

Background

Widespread ceftriaxone antimicrobial resistance (AMR) threatens (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).

Aim

Assess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.

Methods

The five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).

Results

All strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).

Conclusions

AMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

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/content/10.2807/1560-7917.ES.2020.25.43.1900402
2020-10-29
2024-12-21
/content/10.2807/1560-7917.ES.2020.25.43.1900402
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References

  1. Public Health England (PHE). Antimicrobial resistance in Neisseria gonorrhoeae in England and Wales. Key findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2018). London: PHE; Oct 2019. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/834924/GRASP__2018_report.pdf
  2. Abraha M, Egli-Gany D, Low N. Epidemiological, behavioural, and clinical factors associated with antimicrobial-resistant gonorrhoea: a review. F1000 Res. 2018;7:400.  https://doi.org/10.12688/f1000research.13600.1  PMID: 29636908 
  3. Rowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97(8):548-562P.  https://doi.org/10.2471/BLT.18.228486  PMID: 31384073 
  4. World Health Organization (WHO). Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva: WHO; 2012. Available from: http://apps.who.int/iris/bitstream/10665/44863/1/9789241503501_eng.pdf
  5. Bignell C, Unemo M, Radcliffe K, Jensen JS, Babayan K, Barton S, et al. , European STI Guidelines Editorial Board. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2013;24(2):85-92.  https://doi.org/10.1177/0956462412472837  PMID: 24400344 
  6. Bignell C, Fitzgerald M, Guideline Development Group. British Association for Sexual Health and HIV UK. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS. 2011;22(10):541-7.  https://doi.org/10.1258/ijsa.2011.011267  PMID: 21998172 
  7. Fifer H, Saunders J, Soni S, Sadiq ST, FitzGerald M. 2019. British Association for Sexual Health and HIV national guideline for the managementof infection with Neisseria gonorrhoeae (2019). British London: Association for Sexual Health and HIV. 2019. Available from: https://www.bashhguidelines.org/media/1208/gc-2019.pdf
  8. Fifer H, Natarajan U, Jones L, Alexander S, Hughes G, Golparian D, et al. Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea. N Engl J Med. 2016;374(25):2504-6.  https://doi.org/10.1056/NEJMc1512757  PMID: 27332921 
  9. Low N, Unemo M. Molecular tests for the detection of antimicrobial resistant Neisseria gonorrhoeae: when, where, and how to use? Curr Opin Infect Dis. 2016;29(1):45-51.  https://doi.org/10.1097/QCO.0000000000000230  PMID: 26658656 
  10. O’Neill J. Rapid Diagnostics: stopping unnecessary use of antibiotics. London: Review on Antimicrobial Resistance; Oct 2015. Available from: http://amr-review.org/sites/default/files/Rapid%20Diagnostics%20-%20Stopping%20Unnecessary%20use%20of%20Antibiotics.pdf
  11. World Health Organization (WHO). Simple / Rapid tests. Geneva: WHO. [Accessed: Jul 2016]. Available from: http://www.who.int/diagnostics_laboratory/faq/simple_rapid_tests/en/
  12. Sadiq ST, Mazzaferri F, Unemo M. Rapid accurate point-of-care tests combining diagnostics and antimicrobial resistance prediction for Neisseria gonorrhoeae and Mycoplasma genitalium. Sex Transm Infect. 2017;93(S4):S65-8.  https://doi.org/10.1136/sextrans-2016-053072  PMID: 28684610 
  13. Sadiq ST, Dave J, Butcher PD. Point-of-care antibiotic susceptibility testing for gonorrhoea: improving therapeutic options and sparing the use of cephalosporins. Sex Transm Infect. 2010;86(6):445-6.  https://doi.org/10.1136/sti.2010.044230  PMID: 20940156 
  14. Herbst de Cortina S, Bristow CC, Joseph Davey D, Klausner JD. A Systematic Review of Point of Care Testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Infect Dis Obstet Gynecol. 2016;2016:4386127.  https://doi.org/10.1155/2016/4386127  PMID: 27313440 
  15. SpeeDx. ResistancePlus GC.Australia: SpeeDx. [Accessed: 1 Mar 2020]. Available from: https://plexpcr.com/resistanceplus-gc/
  16. National Institute for Health Research (NIHR). Invention for Innovation grant: A Point of Care Antimicrobial Resistance test for Neisseria gonorrhoeae and Mycoplasma genitalium infection. Ensuring accurate therapy and antibiotic stewardship in sexual health medicine. Reference: II-LB-0214-20005. Available from: https://nihr.opendatasoft.com/explore/dataset/infonihr-open-dataset/table/?disjunctive.programme_type&disjunctive.project_status&disjunctive.programme&disjunctive.rgn17nm&disjunctive.pcon17nm&disjunctive.ccg18nm&disjunctive.ctry17cd&disjunctive.funder&disjunctive.acronym&disjunctive.ctry17nm&disjunctive.ccg19nm&disjunctive.lad19nm&disjunctive.pcon18nm&q=antimicrobial+resistance
  17. Harding-Esch EM, Cousins EC, Chow SC, Phillips LT, Hall CL, Cooper N, et al. A 30-minute nucleic acid amplification point-of-care test for genital Chlamydia trachomatis infection in women: a prospective, multi-centre study of diagnostic accuracy. EBioMedicine. 2018;28:120-7.  https://doi.org/10.1016/j.ebiom.2017.12.029  PMID: 29396306 
  18. Public Health England (PHE). Making it work. A guide to whole system commissioning for sexual health, reproductive health and HIV. London: PHE; Mar 2015. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/408357/Making_it_work_revised_March_2015.pdf
  19. Pond MJ, Hall CL, Miari VF, Cole M, Laing KG, Jagatia H, et al. Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy. J Antimicrob Chemother. 2016;71(4):897-902.  https://doi.org/10.1093/jac/dkv432  PMID: 26817487 
  20. Allan-Blitz LT, Humphries RM, Hemarajata P, Bhatti A, Pandori MW, Siedner MJ, et al. Implementation of a Rapid Genotypic Assay to Promote Targeted Ciprofloxacin Therapy of Neisseria gonorrhoeae in a Large Health System. Clin Infect Dis. 2017;64(9):1268-70. PMID: 28034887 
  21. Eyre DW, De Silva D, Cole K, Peters J, Cole MJ, Grad YH, et al. WGS to predict antibiotic MICs for Neisseria gonorrhoeae. J Antimicrob Chemother. 2017;72(7):1937-47.  https://doi.org/10.1093/jac/dkx067  PMID: 28333355 
  22. Unemo M, Bradshaw CS, Hocking JS, de Vries HJC, Francis SC, Mabey D, et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis. 2017;17(8):e235-79.  https://doi.org/10.1016/S1473-3099(17)30310-9  PMID: 28701272 
  23. Public Health England (PHE). Sexually transmitted infections (STIs): annual data tables, 2006-2015. London: PHE. [Accessed: 1 Mar 2020]. Available from: https://www.gov.uk/government/statistics/sexually-transmitted-infections-stis-annual-data-tables
  24. Public Health England (PHE). Table 7: STI diagnoses & partner notification, 2012 - 2015. London: PHE. [Accessed: 1 Mar 2020]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/534562/2015_Table_7_STI_diagnoses___partner_notification__2012-2015.pdf
  25. Herzog SA, Heijne JC, Althaus CL, Low N. Describing the progression from Chlamydia trachomatis and Neisseria gonorrhoeae to pelvic inflammatory disease: systematic review of mathematical modeling studies. Sex Transm Dis. 2012;39(8):628-37.  https://doi.org/10.1097/OLQ.0b013e31825159ff  PMID: 22801346 
  26. Gaydos CA, Van Der Pol B, Jett-Goheen M, Barnes M, Quinn N, Clark C, et al. , CT/NG Study Group. Performance of the Cepheid CT/NG Xpert Rapid PCR Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae. J Clin Microbiol. 2013;51(6):1666-72.  https://doi.org/10.1128/JCM.03461-12  PMID: 23467600 
  27. Harding-Esch EM, Fuller SS, Christine Chow SL, Nori AV, Harrison MA, Parker M, et al. Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multi-centre cross-sectional pre-clinical evaluation. Clin Microbiol Infect. 2019;25(3):380e1-380.e7. http://dx.doi.org/ https://doi.org/10.1016/j.cmi.2018.06.003  PMID: 29906594 
  28. Turner KM, Round J, Horner P, Macleod J, Goldenberg S, Deol A, et al. An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England. Sex Transm Infect. 2014;90(2):104-11.  https://doi.org/10.1136/sextrans-2013-051147  PMID: 24273127 
  29. Public Health England (PHE). Surveillance of antimicrobial resistance in Neisseria gonorrhoeae in England and Wales. Key findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). London: PHE; 2017. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/651636/GRASP_Report_2017.pdf
  30. Adams EJ, Ehrlich A, Turner KM, Shah K, Macleod J, Goldenberg S, et al. Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK. BMJ Open. 2014;4(7):e005322.  https://doi.org/10.1136/bmjopen-2014-005322  PMID: 25056977 
  31. Harding-Esch EM, Nori AV, Hegazi A, Pond MJ, Okolo O, Nardone A, et al. Impact of deploying multiple point-of-care tests with a ‘sample first’ approach on a sexual health clinical care pathway. A service evaluation. Sex Transm Infect. 2017;93(6):424-9.  https://doi.org/10.1136/sextrans-2016-052988  PMID: 28159916 
  32. Atkinson LM, Vijeratnam D, Mani R, Patel R. ‘The waiting game’: are current chlamydia and gonorrhoea near-patient/point-of-care tests acceptable to service users and will they impact on treatment? Int J STD AIDS. 2016;27(8):650-5.  https://doi.org/10.1177/0956462415591414  PMID: 26092579 
  33. Personal Social Services Research Unit (PSSRU). Unit Costs of Health and Social Care 2015. Kent: PSSRU; 2015. Available from: http://www.pssru.ac.uk/project-pages/unit-costs/2015/2015 [
  34. National Institute for Health and Care Excellence (NICE) British National Formulary. (BNF). London: NICE. [Accessed 29 Sept 2016]. Available from: https://www.evidence.nhs.uk/formulary/bnf/current
  35. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346(mar25 1):f1049.  PMID: 23529982 
  36. Fingerhuth SM, Low N, Bonhoeffer S, Althaus CL. Detection of antibiotic resistance is essential for gonorrhoea point-of-care testing: a mathematical modelling study. BMC Med. 2017;15(1):142.  https://doi.org/10.1186/s12916-017-0881-x  PMID: 28747205 
  37. Turner KM, Christensen H, Adams EJ, McAdams D, Fifer H, McDonnell A, et al. Analysis of the potential for point-of-care test to enable individualised treatment of infections caused by antimicrobial-resistant and susceptible strains of Neisseria gonorrhoeae: a modelling study. BMJ Open. 2017;7(6):e015447.  https://doi.org/10.1136/bmjopen-2016-015447  PMID: 28615273 
  38. Zienkiewicz AK, Verschueren van Rees N, Homer M, Ong JJ, Christensen H, Hill D, et al. Agent-based modelling study of antimicrobial-resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment. Sex Health. 2019;16(5):514-22.  https://doi.org/10.1071/SH18235  PMID: 31476277 
  39. Hui BB, Ryder N, Su JY, Ward J, Chen MY, Donovan B, et al. Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings. PLoS One. 2015;10(7):e0133202.  https://doi.org/10.1371/journal.pone.0133202  PMID: 26181042 
  40. Tuite AR, Gift TL, Chesson HW, Hsu K, Salomon JA, Grad YH. Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea. J Infect Dis. 2017;216(9):1141-9.  https://doi.org/10.1093/infdis/jix450  PMID: 28968710 
  41. Toskin I, Govender V, Blondeel K, Murtagh M, Unemo M, Zemouri C, et al. Call to action for health systems integration of point-of-care testing to mitigate the transmission and burden of sexually transmitted infections. Sex Transm Infect. 2020;96(5):342-7.  https://doi.org/10.1136/sextrans-2019-054358  PMID: 32241905 
  42. Davies B, Turner KME, Frølund M, Ward H, May MT, Rasmussen S, et al. , Danish Chlamydia Study Group. Risk of reproductive complications following chlamydia testing: a population-based retrospective cohort study in Denmark. Lancet Infect Dis. 2016;16(9):1057-64.  https://doi.org/10.1016/S1473-3099(16)30092-5  PMID: 27289389 
  43. Golparian D, Rose L, Lynam A, Mohamed A, Bercot B, Ohnishi M, et al. Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018. Euro Surveill. 2018;23(47).  https://doi.org/10.2807/1560-7917.ES.2018.23.47.1800617  PMID: 30482267 
  44. Eyre DW, Sanderson ND, Lord E, Regisford-Reimmer N, Chau K, Barker L, et al. Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Euro Surveill. 2018;23(27).  https://doi.org/10.2807/1560-7917.ES.2018.23.27.1800323  PMID: 29991383 
  45. European Centre for Disease Prevention and Control (ECDC). Extensively drug-resistant (XDR) Neisseria gonorrhoeae in the United Kingdom and Australia. Stockholm: ECDC. 7 May 2018. Available from: https://ecdc.europa.eu/sites/portal/files/documents/RRA-Gonorrhoea%2C%20Antimicrobial%20resistance-United%20Kingdom%2C%20Australia.pdf
  46. Public Health England (PHE). Surveillance of antimicrobial resistance in Neisseria gonorrhoeae. Key findings from the ‘Gonococcal resistance to antimicrobials surveillance programme’ (GRASP) and related surveillance data. London: PHE; 2015. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/476582/GRASP_2014_report_final_111115.pdf
  47. Huntington SE, Burns RM, Harding-Esch E, Harvey MJ, Hill-Tout R, Fuller SS, et al. Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees. BMJ Open. 2018;8(9):e020394.  https://doi.org/10.1136/bmjopen-2017-020394  PMID: 30201794 
  48. Monthly Average Rates London OFX. UKForex Limited. [Accessed: 9 Mar 2020]. Available from: https://www.ofx.com/en-gb/forex-news/historical-exchange-rates/monthly-average-rates/
  49. Office for National Statistics (ONS). Consumer price inflation time series. London: ONS. [Accessed: 9 Mar 2020]. Available from: https://www.ons.gov.uk/economy/inflationandpriceindices/datasets/consumerpriceindices
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