TY - JOUR
T1 - Projecting the development of antimicrobial resistance in Neisseria gonorrhoeae from antimicrobial surveillance data: a mathematical modelling study
AU - Riou, Julien
AU - Althaus, Christian L.
AU - Allen, Hester
AU - Cole, Michelle J.
AU - Grad, Yonatan H.
AU - Heijne, Janneke C. M.
AU - Unemo, Magnus
AU - Low, Nicola
PY - 2023/4/20
Y1 - 2023/4/20
N2 - BackgroundThe World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when >= 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae.MethodsWe used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000-2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution.ResultsThe single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected >= 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7-44.8%) among HMW and 19.6% (95%CrI: 2.6-54.4%) among MSM by 2030.ConclusionsNew first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.
AB - BackgroundThe World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when >= 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae.MethodsWe used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000-2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution.ResultsThe single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected >= 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7-44.8%) among HMW and 19.6% (95%CrI: 2.6-54.4%) among MSM by 2030.ConclusionsNew first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.
KW - Neisseria gonorrhoeae
KW - Antimicrobial resistance
KW - Minimum inhibitory concentration
KW - Surveillance
KW - Mathematical model
KW - MULTIDRUG-RESISTANT
KW - CEFIXIME
KW - CEFTRIAXONE
KW - SUSCEPTIBILITY
U2 - 10.1186/s12879-023-08200-4
DO - 10.1186/s12879-023-08200-4
M3 - Article
C2 - 37081443
SN - 1471-2334
VL - 23
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 252
ER -