Biomedical subjects

Magnus Unemo

Publications and source records attributed to Magnus Unemo.

3 recordsLinked to original sources

PubMed2026

Novel potential treatment options for infections caused by multi-drug and extensively drug-resistant Neisseria gonorrhoeae strains.

INTRODUCTION: Neisseria gonorrhoeae has evolved antimicrobial resistance (AMR) since antimicrobial treatment of gonorrhea was introduced. The AMR development is driven by the bacterium's high capacity for genetic adaptation, antimicrobial overuse and misuse, and insufficient surveillance. Novel therapeutic options are urgently needed. AREAS COVERED: This review summarizes novel gonorrhea treatment options, with special emphasis on the novel oral antimicrobials zoliflodacin and gepotidacin that obtained US FDA-approval for treatment of uncomplicated urogenital gonorrhea in December 2025. It also highlights compounds in early clinical or preclinical development that have demonstrated promising in vitro activity against N. gonorrhoeae. EXPERT OPINION: Zoliflodacin and gepotidacin have the potential to optimize gonorrhea management as oral alternatives to current injectable ceftriaxone. Their successful long-term use will depend on optimized use strategies, including indications, evidence-based approved dosing, adherence, surveillance, and population-specific considerations. Public-health agencies and clinicians will need to balance broad clinical access with antimicrobial stewardship measures to delay the AMR emergence. Looking ahead, gonorrhea management will hopefully shift from empirical, syndromic treatment toward etiology-guided and AMR-informed therapy, driven by advances in rapid point-of-care testing and whole-genome sequencing technologies. Continuous phenotypic and genomic surveillance remains essential to detect early AMR signals, transmission of AMR strains, and inform treatment guidelines.

AMR↗

PubMed2026

Microbiological analysis and whole-genome sequencing of Neisseria gonorrhoeae from the microbiological failures in the international, zoliflodacin, phase 3, clinical trial for treatment of uncomplicated urogenital gonorrhoea: a retrospective, genomic, observational study.

BACKGROUND: Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1). METHODS: In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019-March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L). FINDINGS: All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013-23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10-43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39-77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs. INTERPRETATION: In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests reinfections and not treatment failures. In addition, 59% of the zoliflodacin microbiological failures, all in anogenital sites, had no obvious microbiological explanation based on the low zoliflodacin MICs, previous pharmacodynamic studies, and no evidence of resistance selection after zoliflodacin therapy. A reinfection as the cause for these microbiological failures could not be excluded. We recommend that WGS is implemented in future randomised controlled trials for gonorrhoea treatment to further evaluate possible microbiological failures, exclude reinfections (to avoid underestimating the cure rates), and characterise antimicrobial resistance determinants. FUNDING: GARDP through grants from Germany BMFTR (03KA1831), UK DHSC as part of GAMRIF, Japan MHLW, the Netherlands' Ministry of Health, Welfare and Sport and Directorate-General for International Cooperation, the Federal Office of Public Health of Switzerland, the Canton of Geneva, Switzerland, and Örebro University Hospital, Sweden.

Humans↗

PubMed2025

WHO global gonococcal antimicrobial surveillance programmes, 2019-22: a retrospective observational study.

BACKGROUND: Gonorrhoea and gonococcal antimicrobial resistance (AMR) remain global public health concerns, and enhanced quality-assured global surveillance of gonococcal AMR is imperative to inform management guidelines and public health policies. We aimed to describe the results of surveillance of gonococcal AMR conducted globally by WHO and discuss the actions needed to retain our ability to treat gonorrhoea. METHODS: In this retrospective observational study, we present gonococcal AMR data reported to WHO by 77 countries between Jan 1, 2019, and Dec 31, 2022. Gonococcal isolates were tested for minimum inhibitory concentrations of one to four key antimicrobials (ceftriaxone, cefixime, azithromycin, and ciprofloxacin) in each country. We used breakpoints for resistance and decreased susceptibility to antimicrobials from the European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory and Standards Institute. FINDINGS: 29 (39%) of 75 participating countries reported at least one isolate with resistance or decreased susceptibility to ceftriaxone, 28 (50%) of 56 reported resistance or decreased susceptibility to cefixime, 58 (88%) of 66 reported resistance to azithromycin, and 74 (99%) of 75 reported resistance to ciprofloxacin. Globally, azithromycin resistance is increasing, as is resistance or decreased susceptibility to ceftriaxone and cefixime, especially in the WHO Western Pacific region. Resistance to ciprofloxacin remained very high globally. Since 2017-18, the numbers of reporting countries, examined isolates, and resistant isolates have increased. However, surveillance levels remain inadequate in central America and the Caribbean, eastern Europe, and the WHO African, Eastern Mediterranean, and South-East Asia regions. INTERPRETATION: Global AMR surveillance conducted by WHO is expanding and, in selected countries, improving through standardisation and quality assurance, as well as implementation of extragenital sampling, test of cure, and whole-genome sequencing. This approach provides evidence-based data for management guidelines and public health policies. Improvements in prevention, early diagnosis, treatment of patients and their contacts, surveillance (of infection rates, AMR, treatment failures, and antimicrobial use), and antimicrobial stewardship are essential. WHO supports this work through several global action plans on AMR, new global gonorrhoea treatment recommendations, surveillance, and research. FUNDING: None.

Neisseria gonorrhoeae↗