None listed
Conditions
Brief summary
Every day, more than one million people globally are diagnosed with the four most common non-viral sexually transmitted infections (STIs) and gonorrhoea and chlamydia are the two most common bacterial STIs. In Australia, rates are at increasing rapidly with their highest levels in recent years. Infections in women can cause infertility, and in both sexes, increase HIV acquisition and transmission. Treatment failure is an increasing issue and may be due to factors related to the bacteria (e.g. antibiotic resistance), the individual (e.g. immune response, vomiting/diarrhoea) or how the body processes the drug (its ‘pharmacokinetics’, or PK). Antibiotic resistance for STIs has developed so rapidly that in 2017, the World Health Organization (WHO) declared resistant gonorrhoea as an urgent global threat with the real danger that it may soon be untreatable. We now know that treatment failures occur more often at non-genital (‘extra-genital’) sites such as the mouth or rectum, with current treatment cure for chlamydia or gonorrhoea being up to 20% lower than at the genital site. We also know the mouth/oropharynx drives STI transmission through oral sex, kissing and use of saliva during sex so effective treatments for non-genital infections are critical to stop ongoing transmission. Rectal infections in women can result in persisting vaginal infection from cross contamination between the two sites. There are only a few new drugs in development to treat STIs, but they are many years away and may not be sufficiently effective, especially not for the mouth/oropharynx. Therefore, clinicians must optimise what drugs we have now, but without clinical trial evidence, they must rely on pharmacokinetic (PK) data to guide this decision making. However, there are few PK data available for the mouth or rectum. This project will develop innovative techniques to generate the first comprehensive data in the mouth and rectum for four commonly used antibiotics used to treat STIs – cefixime, ceftriaxone, ciprofloxacin, azithromycin and doxycycline. After this we will apply these methods to emerging drugs currently being tested in trials that have not been marketed yet. This is to ensure new drugs in the pipeline will be effective against STIs. These data will address the urgent global call for data to inform STI treatment guidelines.
Interventions
INFECTED participants: Participants diagnosed with chlamydia will be treated with oral doxycycline 100mg twice a day for 7 days. Survey and pill count will be undertaken at the last follow up to determine adherence.
Those diagnosed with gonorrhoea will be given one of the treatments below as per recommended guidelines
- ceftriaxone 500mg (in 2mL 1% lignocaine) intramuscularly PLUS oral azithromycin 2g as single doses. Azithromycin can also be given as 1g dose followed by 1g 6-12 hours later (Au
INFECTED participants: Participants diagnosed with chlamydia will be treated with oral doxycycline 100mg twice a day for 7 days. Survey and pill count will be undertaken at the last follow up to determine adherence. Those diagnosed with gonorrhoea will be given one of the treatments below as per recommended guidelines - ceftriaxone 500mg (in 2mL 1% lignocaine) intramuscularly PLUS oral azithromycin 2g as single doses. Azithromycin can also be given as 1g dose followed by 1g 6-12 hours later (Australian STI Management Guidelines for use in primary care 2018). Ceftriaxone injection and the first 1g dose of azithromycin will administered/directly observed by the nurse. The second 1g dose of azithromycin will be assured by sending a reminder sms to take the dose. The timing of the second dose will also be recorded. If the 2g dose is taken all at once, this will be directly observed. - ceftriaxone 1g (in 3.5mL 1% lignocaine) intramuscularly as single dose (2020 European Guidelines for the diagnosis and treatment of gonorrhoea in adults AND 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae). Ceftriaxone injection will be directly administered by the nurse. - oral cefixime 400mg as a single dose when susceptibility is known (WHO GUIDELINES FOR THE Treatment of Neisseria gonorrhoeae 2016). The dose will be taken under direct observation by the nurse. - oral ciprofloxacin 500mg as a single dose when susceptibility is known (2020 European Guidelines for the diagnosis and treatment of gonorrhoea in adults). The dose will be taken under direct observation by the nurse. NON-INFECTED participants: In addition to participants diagnosed with chlamydia or gonorrhoea, we will also recruit healthy, non-infected participants. Non-infected participants will be given the same antibiotics as for infected participants but no susceptibility testing will be needed for cefixime or ciprofloxacin i.e. healthy individuals will be given below. The choice of antibiotic prescribed is based on the timing of the participants recruitment - with each of the 5 drugs being studied being equally distributed across the total target sample size i.e. consecutive, block allocation in order of drugs listed below. - oral doxycycline 100mg twice a day for 7 days (Australian STI Management Guidelines for use in primary care 2018). Survey and pill count will be undertaken at the last follow up to determine adherence. - ceftriaxone 500mg (in 2mL 1% lignocaine) intramuscularly PLUS oral azithromycin 2g as single doses. Azithromycin can also be given as 1g dose followed by 1g 6-12 hours later (Australian STI Management Guidelines for use in primary care 2018). Ceftriaxone injection and the first 1g dose of azithromycin will administered/directly observed by the nurse. The second 1g dose of azithromycin will be assured by sending a reminder sms to take the dose. The timing of the second dose will also be recorded. If the 2g dose is taken all at once, this will be directly observed. - ceftriaxone 1g (in 3.5mL 1% lignocaine) intramuscularly as single dose (2020 European Guidelines for the diagnosis and treatment of gonorrhoea in adults AND 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae). Ceftriaxone injection will be directly administered by the nurse. - oral cefixime 400mg as a single dose (WHO GUIDELINES FOR THE Treatment of Neisseria gonorrhoeae 2016). The dose will be taken under direct observation by the nurse. - oral ciprofloxacin 500mg as a single dose (2020 European Guidelines for the diagnosis and treatment of gonorrhoea in adults). The dose will be taken under direct observation by the nurse.
Sponsors
University of Melbourne
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(1) Men or women aged 18 years or older who test positive for rectal and/or oropharyngeal infections with CT or NG (they cannot have both infections) using NAAT or culture methods OR (2) healthy (non-infected) men and women. Both healthy and infected participants must have (a) Adequate English and comprehension to give informed consent (b) Able to attend all follow up visits (c) Those with gingival or periodontal disease/caries are eligible since >30% of population have these conditions (d) Medicare card (e) fully vaccinated for COVID-19
Exclusion criteria
(1) Oral antibiotic use in the last 4 weeks (2) widespread mucosal ulcerations by clinical examination. (3) Infection with both CT and NG) i.e. only single infections at one site are eligible (4) Infection at the same site with Mycoplama genitalium (5) Known contraindications or interactions with any of the treatments (6) Pregnant or breastfeeding women (7) Past participants in this trial (8) transgender people (9) HIV positive participants with CD4 counts less than 250 cells/mm3 Healthy, non-infected participants will not have other infections (CT and NG) including Mycoplama genitalium.
Outcome results
None listed