Patients with cirrhosis have reduced gut bacterial diversity and a gut microbiota dominated by pathobionts. These changes, coupled with increased gut permeability and bacterial translocation, increase susceptibility to infection and death. There is also considerable concern that high antimicrobial exposure in the cirrhotic population drives the development of antimicrobial resistance (AMR). We previously performed a randomised feasibility trial of endoscopically administered jejunal faecal microbiota transplant (FMT) slurry derived from stringently screened donors, and showed it to be safe and well-tolerated in patients with cirrhosis (PROFIT Trial: NCT02862249). FMT was associated with reduced enteropathogenic bacteria in the gut, augmented ammonia excretion, ameliorated systemic inflammation, and enhanced innate immune responses to pathogen challenge. The trial was not powered to detect differences in clinical outcomes. The PROMISE study will evaluate the efficacy of lyophilised encapsulated FMT to reduce infection, decompensating events and mortality in patients with cirrhosis secondary to alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and metabolic dysfunction and alcohol-related liver disease (MetALD). The PROMISE study is a phase 3 multicentre, randomised, double-blinded, placebo-controlled trial that will evaluate encapsulated lyophilised FMT in 300 participants with ALD, MetALD or MASLD cirrhosis (Model for End-Stage Liver Disease Sodium (MELD-Na) score 8–16). Participants will be randomly allocated (1:1) to receive FMT or matched placebo capsules every 91 days for 21 months, with 24-month follow-up. The primary endpoint is time-to-infection or decompensating event resulting in presentation to the emergency department or hospitalisation. Secondary endpoints include all hepatic decompensation, all-cause infection, antibiotic usage, incidence of AMR, hospitalisation rates, liver disease severity scores, quality of life scores, Hospital Anxiety and Depression Scale score (HADS), alcohol use, and mortality. Mechanistic endpoints include quantification of plasma bacterial DNA, plasma and faecal cytokines/biomarkers, plasma and faecal metabolome, faecal proteome, faecal microbiome composition and diversity (including resistome) and monocyte and mucosal-associated invariant T (MAIT) cell frequency, phenotype and function. Recruitment commenced in June 2023. Results will be disseminated via peer-reviewed journals, international conferences and patient support groups. The PROMISE study will assess the efficacy and evaluate the mechanisms of action of FMT in patients with ALD, MASLD and MetALD cirrhosis. FMT may provide an alternative non-antibiotic treatment for these patients through ecological reconstitution of microbial balance. ISRCTN, ISRCTN17863382. Registered on 25th March 2022, https://www.isrctn.com/ISRCTNISRCTN17863382. ClinicalTrials.gov NCT06461208. Registered on 4th June 2024, https://clinicaltrials.gov/study/NCT06461208#study-overview.
BACKGROUND:Faecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (CDI); its use is increasingly being investigated for other indications. Although regional surveys and national registries have provided insight into local practices, a comprehensive global overview of FMT access, implementation and governance is lacking. METHODS:A survey regarding key aspects related to FMT use was disseminated electronically to members of the World Gastroenterology Organization, European FMT Network and International Society of Infectious Diseases. Responses were analysed both descriptively and using appropriate statistical methods. FINDINGS:A total of 80 responses were obtained from 55 countries. FMT was available in significantly more Tier 1/2 than Tier 3/4 nations (24/28 vs 8/27; P < 0.001). In countries lacking access to FMT, reasons included: lack of expertise/infrastructure; financial constraints; regulatory uncertainty; and perceived lack of clinical need. Most countries using FMT employed both upper and lower gastrointestinal administration routes; 18/32 (56%) used capsulised FMT. Almost all countries with access to FMT used it to treat CDI, albeit with different thresholds for the number of CDI episodes prior to use. There were many non-CDI indications for FMT in current use. Payment for stool donation was reported by 10 countries. INTERPRETATION:This is the first global overview of FMT availability and governance, highlighting substantial international inequities and considerable heterogeneity in regulation, clinical use, donor screening and cost. Standardization of practice and targeted support for lower-income countries is needed to ensure equitable access and to promote safe, high-quality delivery as FMT and microbiome-based therapeutics continue to evolve.
BACKGROUND:Colonization of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonization resistance (CR)-the ability to prevent or limit the establishment of pathogens, including MDROs-through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures. OBJECTIVES:To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonization and infection, and to highlight implications for clinical practice, policy, and research. SOURCES:PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists. CONTENT:CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, nonantimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonization and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR-such as diet-based strategies, probiotics, and faecal microbiota transplant-show promise but require robust and repeated, context-specific evaluation. IMPLICATIONS:Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.
Lyophilised encapsulated faecal microbiota provides a practical and cost-effective treatment option to patients with recurrent Clostridioides difficile infection. This study focused on quality assurance of an enteric-coated capsule formulation of FMT as a medicinal product by evaluating bacterial composition, diversity and viability through manufacturing steps and upon product storage at a range of temperatures. Faecal donations from pre-screened healthy individuals (n = 5) were processed according to a published protocol into one or more treatments; 5 capsules = 1 treatment dose/patient. Culture-independent next-generation 16S rRNA gene sequencing was used to speciate and quantify bacteria using a live-dead cell separation method to discriminate the viable cell load. Species diversity in donor stools aligned with other healthy gut microbiome and remained unchanged through the manufacturing process and after storage at -80 °C for 36 weeks. While diversity indices were consistent, a notable difference was observed between viable and total microbiome, particularly in species richness, which decreased when non-viable or compromised cells were excluded from analysis. Anaerobic species exhibited minimal viability loss despite processing in an aerobic environment. Furthermore, capsules were stable with storage at -20 °C and 2-8 °C, with no significant reduction of total live bacterial load after 24 weeks. In summary, 'live-dead' culture-independent analysis was used to characterise the viable faecal microbiome, which retained a diversity of bacterial species, including anaerobes, through manufacture and after storage in capsules for up to 36 weeks. These data support the comparable effectiveness of lyophilised encapsulated FMT to other formulations and delivery methods.
BACKGROUND:Periodic manual measurement of water temperatures to demonstrate sufficient control of waterborne pathogens is labour intensive and does not provide a comprehensive overview of the whole water distribution system. In particular, low-use outlets (which result in water stagnancy and risk of growth of opportunistic premise plumbing pathogens) may be difficult to identify using such a limited dataset. Continuous remote sensor water temperature monitoring systems are used increasingly to obtain a more accurate dataset. METHODS:A continuous remote sensor water temperature monitoring system was installed to the hot and cold water supply of 15 clinical handwash basins in an intensive care unit to monitor usage and temperature fluctuations over 100 days. RESULTS:Two clinical handwash basins were clearly identified as low use and were unused on multiple occasions for periods >24 h. This was likely related to the poor architectural design of the ward, placement of the outlets and lack of space. These two outlets were decommissioned and a further 100-day period of data monitoring was observed. The total number of days without activation decreased by 55% overall for the hot water supply (82 vs 37 days without activation) and by 36% overall for the cold water supply (193 vs 124 days without activation). CONCLUSION:Continuous remote sensor water temperature monitoring systems can generate a more comprehensive and accurate dataset that is difficult to achieve with periodic manual monitoring. This allowed two outlets to be decommissioned, which was associated with improved water utilization across the rest of the unit.
OBJECTIVES:The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections, which can be challenging to treat with excess morbidity and mortality compared to antimicrobial-susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst faecal microbiota transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety, and efficacy. METHODS:Population: Patients with invasive infection with extended-spectrum beta-lactamase (ESBL-) or carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage. INTERVENTION:Three doses of encapsulated lyophilised FMT. COMPARATOR:Matched placebo capsules. OUTCOMES:Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis. RESULTS:Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT, but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups, with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p = 0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p = 0.05) and change in strain dominance within MDRO at the species-level. CONCLUSIONS:Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.
BACKGROUND:Candidozyma (Candida) auris is a multi-drug-resistant fungal pathogen associated with protracted, costly hospital outbreaks. Conventional patient-level screening is resource-intensive and may not be cost effective. Wastewater surveillance may offer a pragmatic, ward-level approach to early detection. AIMS:To determine whether C. auris can be reliably detected in ward wastewater during an ongoing hospital outbreak; to compare the performance of culture- and PCR-based wastewater methods with patient-level colonization screening. METHODS:Between August and September 2024, during an ongoing C. auris UK hospital outbreak, a point-prevalence survey was conducted alongside sampling of 12 corresponding ward sluices. Wastewater grab samples and environmental swabs from sluice sinks, macerators and handwash sinks were investigated by direct culture and enrichment broth, as well as AurisID® real-time PCR assay on the centrifuged pellet. Whole-genome sequencing was performed on matched patient and wastewater isolates to assess genetic relatedness. FINDINGS:Using the detection of ≥1 C. auris patient on a ward as the standard, sensitivity of culture was 75% (95% confidence interval (CI) 35-97%) and specificity 100% (95% CI 40-100%); AurisID® PCR sensitivity was 100% (95% CI 63-100%) and specificity 75% (95% CI 19-99%). Whole-genome sequencing analysis demonstrated clustering and clonality of wastewater and patient isolates (<10 single-nucleotide polymorphisms difference). CONCLUSION:We report the first detection of C. auris from hospital ward wastewater using culture and PCR. Screening ward wastewater may offer a sensitive, cost-effective alternative to individual patient screening in low-prevalence settings, supporting earlier ward-level detection: prospective, longitudinal studies are needed.
Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.
Background: Hospital drains and water interfaces are implicated in nosocomial transmission of pathogens. Metagenomics can assess the microbial composition and presence of antimicrobial resistance genes in drains ('the drainome') but studies applying these methods longitudinally and to assess infection control interventions are lacking. Aim: To apply long-read metagenomics coupled with microbiological measurements to investigate the drainome and assess the effects of a peracetic-acid-containing decontamination product. Methods: Twelve-week study in three phases: a baseline phase, an intervention phase of enhanced decontamination with peracetic acid, and a post-intervention phase. Five hospital sink drains on an intensive care unit were sampled twice weekly. Each sample had: (1) measurement of total viable count (TVC); (2) metagenomic analyses including (i) taxonomic classification of bacteria and fungi (ii), antibiotic resistance gene detection, (iii) plasmid identification; and (3) immunochromatographic detection of antimicrobial residues. Findings: Overall TVCs remain unchanged in the intervention phase (+386 cfu/mL, SE 705, P = 0.59). There was a small but significant increase in the microbial diversity in the intervention phase (-0.07 in Simpson's index, SE 0.03, P = 0.007), which was not sustained post-intervention (-0.05, SE 0.03, P = 0.08). The intervention was associated with increased relative abundance of the Pseudomonas genus (18.3% to 40.5% (+22.2%), SE 5.7%, P < 0.001). Extended spectrum beta-lactamases were found in all samples, with NDM carbapenemase found in three drains in six samples. Antimicrobial residues were detectedin a large proportion of samples (31/115, 27%), suggesting use of sinks for non-handwashing activities. Conclusion: Metagenomics and other measurements can determine the composition of the drainome and assess the effectiveness of decontamination interventions.
Abstract Background Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing. Methods The human cells from respiratory samples are lysed mechanically using 1.4 mm zirconium-silicate spheres and the human DNA is depleted using a nonspecific endonuclease. The RNA is converted to dsDNA to allow the simultaneous sequencing of DNA and RNA. Results The method decreases human DNA concentration by a median of eight Ct values while detecting a broad range of RNA & DNA viruses, bacteria, including atypical pathogens (Legionella, Chlamydia, Mycoplasma) and fungi (Candida, Pneumocystis, Aspergillus). The first automated reports are generated after 30 min sequencing from a 7 h end-to-end workflow. Sensitivity and specificity for bacterial detection are 90% and 100%, respectively, and viral detection are 92% and 100% after 2 h of sequencing. Prospective validation on 33 consecutive lower respiratory tract samples from ventilated patients with suspected pneumonia shows 60% concordance with routine testing, detection of additional pathogens in 21% of samples and pathogen genomic assembly achieve for 42% of viruses and 33% of bacteria. Conclusions Although further workflow refinement and validation on samples containing a broader range of pathogens is required, it holds promise as a clinically deployable workflow suitable for evaluation in routine microbiology laboratories.
Introduction: We under took an in-use evaluation of a novel hypochlorous acid-based hand hygiene product with in vitro sporicidal efficacy in a NHS Older Persons inpatient ward setting. Methods: The novel hand hygiene product was implemented for a trial period of seven weeks commending in September 2023. Healthcare worker (HCW) hands were sampled before and after direct patient care, and after the application of either an alcohol-based handrub (ABHR) (n=50) or the novel product (n=50). Samples were cultured to quantify the total aerobic count (TAC) and presence or absence of MRSA, ESBLs, CREs, and C. difficile. Trends in weekly observational hand hygiene audit results were reviewed, and a survey of HCW views about the new product undertaken. Results: HCW hands had a significantly greater TAC after ABHR (p=0.01) but not after the novel product (p=0.11) compared with their respective baseline counts. 3% of 100 samples grew MRSA or ESBLs after application of the alcohol-based or novel hand hygiene products. No C. difficile was cultured from healthcare worker hands. There was no significant difference in observed hand hygiene compliance. The majority of HCW surveyed preferred the novel product to the alcohol-based hand hygiene product. Discussion: The novel hand hygiene product was more effective than ABHR at reducing the TAC on HCW hands. Poor hand hygiene technique may explain the identification of antibiotic-resistant bacteria on staff hands after ABHR or the novel product. We were not able to evaluate sporicidal efficacy since no C. difficile was cultured from hands.
The periphery of the hospital water system interfaces at multiple points with patients and staff in clinical areas. This comprises mostly of sinks and showers and presents a significant infection control risk. Wastewater drains in particular act as a reservoir of pathogens that can be transmitted to patients. Numerous strategies have been investigated as potential methods to reduce biofilm and bacterial load including regular application of biocidal chemicals. Traditional methods of assessing the efficacy of such products relies on culture based microbiological techniques, usually targeting a limited range of key pathogens. We assessed the efficacy of a peracetic acid containing drain disinfectant product on seven clinical handwash basin drains, taking daily samples over six weeks (before, during and after use of the drain disinfectant product). We used a rapid, culture independent estimation of total bacterial viable count (TVC) to assess efficacy. We applied long read metagenomic sequencing to study the entire drain microbiome, which allowed taxonomic changes to be documented following use of the drain disinfectant product. All samples were found to be heavily contaminated, however the drain disinfectant product reduced the TVC from an estimated mean of 4228 cfu/mL to 2874 cfu/mL. This reduction was sustained in the two weeks following cessation of the product. Long-read metagenomic sequencing showed a microbiome dominated with Gram negative organisms, with some taxonomic shifts in samples before and after application of the drain disinfectant. The impact on hospital-acquired infections from reducing bioburden in hospital drains by approximately a third, along with any associated changes in bacterial composition, needs evaluation in future studies.
Antimicrobial resistance is a global threat to public health. Without proactive intervention, common infections may become untreatable, restricting the types of clinical intervention that can be undertaken and reversing improvements in mortality rates. Effective antimicrobial stewardship represents one approach to restrict the spread of antimicrobial resistance but relies on rapid and accurate diagnostics that minimise the unnecessary use of antibiotics. This is increasingly a key unmet clinical need. In this paper, we describe existing techniques for the detection of antimicrobial resistance, while examining their drawbacks and limitations. We also discuss emerging diagnostic technologies in the field, and the need for standardisation to allow for swifter and more widespread clinical adoption.
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.
Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory condition, characterized by recurrent abscesses and sinus tracts in intertriginous areas. Intravenous (IV) antibiotics are used in cases of severe HS after the failure of conventional therapies, or to optimize patients prior to initiation of biologics or surgery. However, there is limited evidence on the efficacy of IV antibiotics [Join-Lambert O, Coignard-Biehler H, Jais J-P et al. Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients. J Antimicrob Chemother 2016; 71:513–20; Ingram JR, Collier F, Brown D et al. British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018. Br J Dermatol 2019; 180:1009–17]. Our aim was to determine the immediate and long-term impact of IV antibiotics in severe HS and to develop a pre- and post-IV antibiotics assessment and care pathway. We conducted a multicentre retrospective review of patients with HS treated with IV antibiotics at two tertiary HS centres between 2013 and 2022. In total, we included 30 patients (14 females and 16 males), with a mean (SD) age of 42.6 (12.8) years (range 15–66) and a mean (SD) body mass index of 29.96 (7.31) kg m−2. All patients were classified as Hurley stage 3. The majority of patients received ertapenem (n = 24); other antibiotics included ceftriaxone (n = 5) and meropenem (n = 1). Patients had an average of 38.7 days on treatment (range 14–56). There were statistically significant improvements at the completion of antibiotics in biochemical and haematological parameters, including C-reactive protein −27.5 mg L−1 [95% confidence interval (CI) −11 to −57; P < 0.003], white cell counts −1.75 × 109 cells L−1 (95% CI −0.95 to −2.80; P < 0.001) and haemoglobin +7 g L−1 (95% CI 2.5–13; P < 0.005). Dermatology Life Quality Index (out of 30) also improved significantly at completion (−5, 95% CI −1 to −10; P < 0.008). These were all maintained 12 months postcompletion. Clinical severity of HS assessed through pain visual analogue score (VAS), discharge VAS, DERMVAS, overall VAS, and HS Physician Global Assessment showed improvement but did not reach statistical significance. Improvement in discharge VAS [out of 10; −2, 95% CI −1.5 to −4.5 (P < 0.066)] achieved borderline significance. To our knowledge, this is the largest analysis of the efficacy of IV antibiotics in patients with the most severe form of HS (i.e. Hurley stage 3), where we show improvement in clinical parameters and quality of life. The findings of this study should encourage a randomized controlled study to determine conclusive evidence to guide the evidence-based management of severe HS and have informed the development of a more formal assessment pathway.