Dr Ray O’Connor continues his look at recent clinical articles on therapeutics, with an emphasis on antibiotics, postbiotics, and faecal transplantation
Antimicrobial resistance (AMR) is a growing threat to global health, undermining the effectiveness of life-saving antibiotic treatments and placing populations at heightened risk, whether from common infections or routine medical interventions.
The WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) supports countries in building national surveillance systems and generating standardized data to guide public health action. This new WHO report1,2 presents a global analysis of antibiotic resistance prevalence and trends, drawing on more than 23 million bacteriologically confirmed cases of bloodstream infections, urinary tract infections, gastrointestinal infections, and urogenital gonorrhoea. Data were reported by 104 countries in 2023 and 110 countries between 2016 and 2023.
Dr Ray O’Connor
There are several startling findings in the report. For example, in 2023 approximately one-in-six laboratory-confirmed bacterial infections worldwide were caused by bacteria resistant to antibiotics. Median resistance was most common in urinary tract infections (approximately one-in-three) and bloodstream infections (one-in-six). Socioeconomic factors and the strength of health systems are key determinants of the AMR burden, with the frequency of AMR increasing when health systems are weaker.
The report finds a strong inverse correlation between the universal health coverage (UHC) service coverage index (a measure of access to essential health services) and the median percentage of AMR in bloodstream infections.
This pattern points to a pattern in which AMR disproportionately affects countries with weaker health systems and lower income levels. Resistance was highest in Southeast Asia and the Middle East, where one-in-three reported infections were resistant. In Africa one-in-five infections were resistant.
The Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK has just approved gepotidacin (Blujepa). This is the UK’s first new type of antibiotic for urinary tract infections (UTIs) in nearly 30 years. The author of this review article3 points out that UTIs affect half of all women at some point in their lives. However, many no longer respond to the standard antibiotics and it is reported that more than 90 per cent of UTI causing bacteria are now resistant to at least one common medicine.
What about non-antibiotic initiatives for management of recurrent infections? There is a paucity of evidence regarding use of endoscopic sinus surgery and antibiotics in managing chronic rhinosinusitis.
This has contributed to a five-times variation in endoscopic sinus surgery rates, as well as variation in the use of antibiotics. The main aim of this pragmatic, three-arm, randomised, placebo-controlled phase 4 trial4 was to compare the clinical effectiveness of endoscopic sinus surgery or three months of clarithromycin treatment alongside intranasal medication in adults with chronic rhinosinusitis with or without nasal polyps.
Participants were recruited from 20 secondary and tertiary care sites in the UK. 514 participants (181 [35 per cent] female and 333 [65 per cent] male), with chronic rhinosinusitis with nasal polyps (n=410) or chronic rhinosinusitis without nasal polyps (n=104), were recruited and randomly assigned to receive endoscopic sinus surgery (n=171), clarithromycin (n=172), or placebo (n=171), all with intranasal medication.
Sino-Nasal Outcome Test (SNOT-22) quality-of-life scores were assessed. Scores at six months after randomisation were significantly lower in the endoscopic sinus surgery group than in the clarithromycin group and placebo group. Six-month SNOT-22 scores did not differ significantly between participants randomly assigned to clarithromycin versus placebo.
The authors’ conclusion was that endoscopic sinus surgery has clinical effectiveness in patients with chronic rhinosinusitis, providing significantly improved disease-specific quality of life at six months. Conversely, the trial findings do not support routine long-term use of low-dose clarithromycin. Therefore, endoscopic sinus surgery should be recommended if intranasal medication alone is unable to achieve symptom control.
In a related topic we look at the effect of the gut microbiome (often adversely affected by antibiotic usage) on one of the commonest psychological symptoms encountered in practice i.e. depression. Depressive symptoms are common significantly affecting quality of life and posing challenges to treatment.
While pharmacological and psychological therapies remain standard, many patients show limited response. Faecal microbiota transplantation (FMT), which aims to restore gut microbial balance, has emerged as a novel approach for alleviating depressive symptoms by modulating the gut-brain axis.
This systematic review and meta-analysis of randomised trials5 aimed to conduct a comprehensive synthesis and quantitative evaluation of current evidence to elucidate the therapeutic potential of FMT in the management of depressive symptoms. The results were that FMT significantly reduced depressive symptoms. Both oral capsule and direct gastrointestinal administration were effective, with greater effects seen in direct gastrointestinal delivery. Improvements were most notable in the short- to mid-term; effects diminished by six months. Subgroup analysis showed stronger effects in patients with irritable bowel syndrome. The authors conclude that their findings warrant further research.
Finally, a related study looks at the potential role of postbiotics in combatting age related diseases. Dietary patterns have been identified as one of the most important modifiable risk factors for several non-communicable diseases, inextricably linked to the health span of older people. Poor dietary choices may act as triggers for immune responses such as aggravated inflammatory reactions and oxidative stress contributing to the pathophysiology of several ageing hallmarks.
Novel dietary interventions are being explored to restore gut microbiota balance and promote overall health in ageing populations. Probiotics and, most recently, postbiotics, which are products of probiotic fermentation, have been reported to modulate different signalling biomolecules involved in immunity, metabolism, inflammation, and oxidation pathways. This review6 presents evidence-based literature on the effects of postbiotics in promoting healthy ageing and mitigating various age-related diseases.
References:
- World Health Organization. Global antibiotic resistance surveillance report 2025. 2025. https://www.who.int/publications/i/item/9789240116337.
- Wise J. One in six bacterial infections worldwide are now resistant to antibiotics, WHO warns. BMJ 2025;391:r2165 http://doi.org/10.1136/bmj.r2165 Published: 14 October 2025.
- Rose N. A new antibiotic is positive news—but it will take more to stay ahead of superbugs. BMJ 2025;391:r2142 http://doi.org/10.1136/bmj.r2142 Published: 13 October 2025.
- Philpott C et al. The clinical effectiveness of clarithromycin versus endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps (MACRO): a pragmatic, multicentre, three-arm, randomised, placebo controlled phase 4 trial. Lancet 2025; 406: 926–39. DOI: 10.1016/S0140-6736(25)01248-6.
- Zhang X et al. Clinical efficacy of fecal microbiota transplantation in alleviating depressive symptoms: a meta-analysis of randomized trials. Front. Psychiatry 16:1656969. DOI: 10.3389/fpsyt.2025.1656969.
- Hamdi A et al. Postbiotics: A Promising Approach to Combat Age-Related Diseases. Life 2025, 15, 1190. https://doi.org/10.3390/life15081190.