A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on<i>Neisseria gonorrhoeae</i>antimicrobial resistance

Mortimer, Tatum D; Grad, Yonatan H.

doi:10.1101/2023.03.14.23287223

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…Recent genomic studies of N. gonorrhoeae isolates have highlighted the potential for selecting cross-resistance to other antimicrobials with doxycycline use, especially when all tetracycline lineages are selected. 17 , 18 Among MSM populations, the majority of N. gonorrhoeae isolates were found to have intermediate tetracycline MICs, which the authors warned could represent a reservoir for rapid evolution of resistance. 17 …”

Section: Amrmentioning

confidence: 99%

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Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections

Kong

Kenyon

Unemo

2023

Journal of Antimicrobial Chemotherapy

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Rates of sexually transmitted infections (STIs) continue to rise across the world and interventions are essential to reduce their incidence. Past and recent studies have indicated this may be achieved using doxycycline post-exposure prophylaxis (PEP) and this has sparked considerable interest in its use. However, many unanswered questions remain as to its long-term effects and particularly potentially negative impact on human microbiomes and antimicrobial resistance among STIs, other pathogens, and commensals. In this review, we discuss seven areas of concern pertaining to the widespread use of doxycycline PEP.

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Section: Amrmentioning

confidence: 99%

“… 17 , 18 Among MSM populations, the majority of N. gonorrhoeae isolates were found to have intermediate tetracycline MICs, which the authors warned could represent a reservoir for rapid evolution of resistance. 17 …”

Section: Amrmentioning

confidence: 99%

Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections

Kong

Kenyon

Unemo

2023

Journal of Antimicrobial Chemotherapy

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Resistance and prevalence implications of doxycycline post-exposure prophylaxis for gonorrhea prevention in men who have sex with men: a modeling study

Reichert

Grad

2023

Preprint

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Background Doxycycline post-exposure prophylaxis (DoxyPEP) has demonstrated efficacy for prevention of bacterial sexually transmitted infections. To inform policy decisions on the use of DoxyPEP for gonorrhea prevention, we used a mathematical model to investigate its impact on resistance dynamics and the burden of infection in men who have sex with men (MSM). Methods and Findings Using a deterministic compartmental model of gonorrhea transmission in an MSM population, we introduced DoxyPEP at various uptake levels (10-75%) and compared 20-year prevalence and resistance dynamics relative to those at baseline (i.e., no DoxyPEP introduction). Uptake of DoxyPEP resulted in initial drops in the prevalence and incidence of gonorrhea infection, but also accelerated the spread of doxycycline resistance, with increasing DoxyPEP use driving steeper initial declines followed by faster spread of resistance. This resulted in the total loss of DoxyPEP's clinical efficacy within 1-2 decades in almost all scenarios explored. The magnitude by which DoxyPEP initially reduced the prevalence of infection was constrained by the extent of pre-existing doxycycline resistant strains in the population. De novo emergence of doxycycline resistance did not influence these dynamics. Additionally, the implementation of DoxyPEP had minimal impact on extending the clinically useful lifespan of ceftriaxone monotherapy. Conclusions Model findings suggest DoxyPEP can be an effective but short-term solution for reducing the burden of gonorrhea infection, as its selection for doxycycline-resistant strains results in loss of its prophylaxis benefit. Increasing levels of DoxyPEP uptake and higher starting prevalence of doxycycline resistance resulted in faster loss of its efficacy and had little change on extending the clinical lifespan of ceftriaxone for treatment of N. gonorrhoeae infections.

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Estimating changes in antibiotic consumption with the introduction of doxycycline post-exposure prophylaxis in the United States

Roster,

Grad

2023

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Doxycycline as post-exposure prophylaxis (doxy-PEP) reduces the risk of gonorrhea, chlamydia, and syphilis in studies of men who have sex with men (MSM) and transgender women (TGW) on HIV Pre-exposure Prophylaxis (PrEP) and people living with HIV (PLWH)). Doxy-PEP is an important tool to address the increasing burden of sexually transmitted infections (STIs), but there is concern that increased consumption of doxycycline may drive antimicrobial resistance. We estimated the expected increase in antibiotic use in the US under several doxy-PEP prescribing scenarios. We accounted for doses of antibiotics that may be averted due to the prevention of chlamydia, gonorrhea, and syphilis infections by doxy-PEP. Under a scenario of 75% adoption among the eligible population, with rates of consumption similar to the DoxyPEP trial population, monthly antibiotic consumption would increase by around 2.52 million doses, driven by doxy-PEP consumption of 2.58 million doses and less 62.1 thousand antibiotic doses that would otherwise have been used for chlamydia, gonorrhea, and syphilis treatment.

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A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis onNeisseria gonorrhoeaeantimicrobial resistance

Cited by 4 publications

References 12 publications

Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections

Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections

Resistance and prevalence implications of doxycycline post-exposure prophylaxis for gonorrhea prevention in men who have sex with men: a modeling study

Estimating changes in antibiotic consumption with the introduction of doxycycline post-exposure prophylaxis in the United States

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