Researchers are testing a new single-dose pill that could make treating gonorrhea easier as antibiotic resistance rises.
A new antibiotic pill called zoliflodacin could become an important option for treating gonorrhea as the infection grows harder to cure with existing drugs. In a phase 3 clinical trial published in The Lancet, researchers reported that a single oral dose of zoliflodacin worked about as well as the long-used standard approach that relies on two antibiotics: a ceftriaxone injection followed by an oral dose of azithromycin.
Gonorrhea is a common sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. The World Health Organization (WHO) estimated that in 2020 there were 82·4 million new cases worldwide among people aged 15–49 years. Treatment matters because untreated gonorrhea can lead to serious complications, and infection can also increase the risk of acquiring or transmitting HIV. The challenge is that N gonorrhea has gradually developed resistance to every class of antibiotics previously used against it, leaving fewer reliable options.
Surveillance data cited by the researchers describe growing concern in several regions, including reports of rising azithromycin resistance and increasing multidrug resistance, with especially worrying signals involving ceftriaxone susceptibility in places such as Cambodia and Viet Nam.
How Zoliflodacin Works
Zoliflodacin is a first-in-class spiropyrimidinetrione antibiotic that kills the bacteria by disrupting DNA replication, mainly by targeting the GyrB subunit of DNA gyrase. This is distinct from fluoroquinolones, which primarily act on other bacterial targets. Earlier work showed zoliflodacin can remain active in laboratory testing against strains resistant to ciprofloxacin, ceftriaxone, and azithromycin, and modelling supported a single 3 g oral regimen.
The phase 3 trial enrolled more than 900 people across 17 outpatient clinics in five countries (USA, South Africa, Thailand, Belgium, and the Netherlands). Participants received either the new pill or the standard treatment. Results showed that zoliflodacin cured over 90% of infections at genital sites.
Results showed that zoliflodacin cured over 90% of infections at genital sites. The medication was well tolerated, with side effects similar to those seen with current treatments, and no serious safety issues were reported. The investigators also reported no evidence that resistance to zoliflodacin emerged during the trial based on the laboratory findings they tracked from baseline to test of cure.
Zoliflodacin is awaiting review by the U.S. Food and Drug Administration (FDA). If it is approved, the authors argue that a single-dose oral option could strengthen efforts to control drug-resistant gonorrhea, make treatment easier to deliver in more settings (including community-led care), and help protect reproductive health for millions of people by improving access to effective therapy worldwide.
Reference: “Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial” by Alison Luckey, Manica Balasegaram, Lindley A Barbee, Teresa A Batteiger, Helen Broadhurst, Stephanie E Cohen, Sinead Delany-Moretlwe, Henry J C de Vries, Jodie A Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P Mueller, Vimla Naicker, Seamus O’Brien, John P O’Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N Taylor, Magnus Unemo, Zinhle Zwane, Edward W Hook, Keisha De Gouveia, Thembisa Makowa Mkhize, Samantha Siva, Lindy Gumede, Ranmini Kularatne, Venessa Maseko, Shabashini Reddy, Patience Kwedza, Ravesh Singh, Lisha Sookan, Danielle Travill, Kittipoom Chinhiran, Sarinthorn Mongkolrat, Chatnapa Duangdee, Jantawan Satayarak, Siriporn Nonenoy, Supanat Thitipatarakorn, Joseph V Woodring, Wannee Chonwattana, Supawadee Na-pompet, Waropart Pongchaisit, Suwan Sriviriyakul, Tanyaporn Wansom, Aaron Ermel, Lora Fortenberry, Catherine L Cammarata, Rebecca Lillis, Alison Cohee, Ejovwoke Dosunmu, Godfred Masinde, Paula Dixon, Julia C Dombrowski, Olusegun O Soge, Elske Hoornenborg, Alje van Dam, Vicky Cuylaerts, Irith Debaetselier, Angèle Gayet-Ageron, Sarah M. McLeod, Alita Miller, Sarah Cohen, Hilary Johnstone, Lebogang Tshehla, Emilie Alirol, Carmen Au, Cherine Bajjali, Esther Bettiol, Pierre Daram, Amalia Droal, Varalakshmi Elango, Christophe Escot, Markus Heep, Karin Hergarden, Daniel Iniguez, Gabrielle Kornmann, Jean-François Louvion, Manon Manuelli, Jessica Renaux and Mary-Ann Richardson, 11 December 2025, The Lancet.
DOI: 10.1016/S0140-6736(25)01953-1
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3 Comments
hanks for this
If it disrupts DNA gyrase in the bacteria, would not it also disrupt human DNA? For an adult this may be insignificant, but for growing children, infants, newborns, or a fetus, significant disruptions might occur. How is this antibiotic eliminated from the body? Are there any restrictions on its use? Good article.
If it disrupts DNA gyrase in the bacteria, would not it also disrupt human DNA? For an adult this may be insignificant, but for growing children, infants, newborns, or a fetus, signafant disruptions might occur. How is this antibiotic eliminated from the body? Are there any restrictions on its use? Good article.