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New Drug for Old Bug: Addressing AMR and Gonorrhoea

A Spotlight from Charlene Rodrigues, Head of Clinical and Veterinary Sciences Research Pillar of the AMR Centre
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You arrive for your first shift in the paediatric emergency department at a busy London hospital, slightly anxious that winter is coming, the viruses are starting to ramp up in frequency and it may be a busy 12 hours ahead. Your first patient is a newborn, brought by his mother and father, who is only 7 days old but has swollen, red eye lids that are both discharging pus. You are worried about ophthalmia neonatorum and of particular concern here are sexually transmitted infections (STIs) gonorrhoea and chlamydia, so after performing your assessment of the baby, you call the sexual health doctors for advice and they agree to review mum and dad whilst they are in hospital. Dad discloses to you in confidence that he has had some dysuria following a trip to Cambodia and is subsequently treated with ceftriaxone and doxycycline. 

The culture of the pus from the baby’s eyes identifies Neisseria gonorrhoeae and you are glad you started them on ceftriaxone. However, you then notice the antimicrobial susceptibility testing has identified resistance to ceftriaxone and azithromycin, so you call the microbiologist for advice on the next treatment steps for this extremely drug resistant (XDR) N. gonorrhoeae. N. gonorrhoeae is the third most common STI, and of great concern due to increasing development of antimicrobial resistance (AMR) to ciprofloxacin, ceftriaxone and azithromycin. Emergence of XDR isolates from South East Asian regions including Cambodia, potentially leave us with no antibiotics to use. Aside from the public health messaging about safe sexual health practices to reduce STI transmission, there has been interest in the development of other primary prevention strategies, through vaccination, and new therapeutics to offer in XDR cases. 

This month a significant milestone was achieved in new antibiotic development, with the outcomes of a Phase III clinical trial of a novel antibiotic Zoliflodacin. Zoliflodacin has a novel mechanism of action inhibiting type II topoisomerase, essential for bacterial cell growth, and was developed through a public-private partnership between GARDP and Innoviva. The trial took place across five high incidence countries (Belgium, the Netherlands, the US, South Africa and Thailand), enrolling 930 patients (importantly including women, adolescents and people living with HIV) with uncomplicated gonorrhoea. The trial demonstrated non-inferiority of microbiological cure after a single oral dose of Zoliflodacin, as compared with global standard of care gonococcal treatment with single dose IM ceftriaxone and oral azithromycin, The drug was well tolerated, with no serious adverse events or deaths amongst patients.

We now await to see formal approvals, production and distribution of the antibiotic to regions most in need, requiring costs to be accessible accordingly. Future trials need to consider the suitability of the drugs for infants, to address ophthalmia neonatorum caused by XDR N. gonorrhoeae.  Further to the scientific and clinical success of Zoliflodacin, this research and development model offers a cause for optimism for new antibiotic development going forward.

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