Publications
36 results found
Yip AYG, King OG, Omelchenko O, et al., 2023, Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites, Nature Communications, Vol: 14, Pages: 1-20, ISSN: 2041-1723
The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.
Ghani R, Blanco JM, Forlano R, et al., 2022, RELATIVE CHANGE OF <i>ENTEROCOCCUS FAECIUM</i>, SELECTED COMMENSAL BACTERIA AND CYTOKINES ARE SEEN IN PATIENTS COLONIZED WITH MULTIDRUG-RESISTANT ORGANISMS WHO UNDERGO INTESTINAL MICROBIOTA TRANSPLANTATION, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S218-S219, ISSN: 0016-5085
Ghani R, Mullish BH, Davies FJ, et al., 2022, How to adapt an intestinal microbiota transplantation program to reduce the risk of invasive multidrug-resistant infection, Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X
Background:Vulnerable patients with intestinal colonisation of multidrug-resistant organisms (MDROs) are recognised to be at increased risk of invasive MDRO driven infection. Intestinal Microbiota Transplantation (IMT aka FMT) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.Objectives:To describe ‘How to’ establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimising administration and assessment of endpoints.Sources:Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.Content:IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) to take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT occurs when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least two weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonisation as a binary outcome. Repeat IMT is considered case-by-case.Implications:Future research areas should include randomised studies that consider clinical outcomes and cost-effectiveness, and better understa
Ghani R, Mullish BH, Roberts L, et al., 2022, The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases, Gut Microbes, Vol: 14, Pages: 1-22, ISSN: 1949-0976
The intestinal microbiota is recognized to play a role in the defense against infection, but conversely also acts as a reservoir for potentially pathogenic organisms. Disruption to the microbiome can increase the risk of invasive infection from these organisms; therefore, strategies to restore the composition of the gut microbiota are a potential strategy of key interest to mitigate this risk. Fecal (or Intestinal) Microbiota Transplantation (FMT/IMT), is the administration of minimally manipulated screened healthy donor stool to an affected recipient, and remains the major ‘whole microbiome’ therapeutic approach at present. Driven by the marked success of using FMT in the treatment of recurrent Clostridioides difficile infection, he potential use of FMT in treating other infectious diseases is an area of active research. In this Review, we discuss key examples of this treatment based on recent findings relating to the interplay between microbiota and infection, and potential further exploitations of FMT/IMT.
Lythgoe MP, Ghani R, Mullish BH, et al., 2021, The Potential of Faecal Microbiota Transplantation in Oncology, Trends in Microbiology, ISSN: 0966-842X
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988
The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.
Mullish BH, Ghani R, McDonald JAK, et al., 2021, Reply to Woodworth, et al, Clinical Infectious Diseases, Vol: 72, Pages: e924-e925, ISSN: 1058-4838
Mullish BH, Innes AJ, Ghani R, et al., 2021, FECAL MICROBIOTA TRANSPLANT PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT IN PATIENTS COLONIZED WITH MULTI-DRUG RESISTANT ORGANISMS IS ASSOCIATED WITH IMPROVED SURVIVAL, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S168-S169, ISSN: 0016-5085
Ghani R, Mullish BH, McDonald JAK, et al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, ISSN: 1058-4838
Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.
Ghani R, Mullish B, Innes A, et al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID
Innes AJ, Ghani R, Mullish BH, et al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369
Ghani R, Mullish BH, 2020, Decision: Considerations for Use of Fecal Microbiota Transplantation in Special Patient Populations, The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond, Editors: Allegretti, Kassam, Publisher: Slack Incorporated, ISBN: 9781630917500
Ghani R, Mullish BH, McDonald JA, et al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Publisher: Elsevier BV, ISSN: 0016-5085
Ghani R, Mullish BH, Mcdonald J, et al., 2020, Cohort study of Faecal Microbiota Transplantation for patient’s colonised with MDROs - successful prevention of invasive disease despite low decolonisation rates, Access Microbiology, Vol: 2
Ghani R, Mullish BH, Thursz M, et al., 2020, Case-control study of recurrent Extended-Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections (ESBL UTIs): the management challenges, Access Microbiology, Vol: 2
Ghani R, Mullish BH, McDonald J, et al., 2020, Disease prevention not decolonisation: a cohort study for faecal microbiota transplantation for patients colonised with multidrug-resistant organisms, ECCMID 2020
Ghani R, Gan C, Mullish BH, et al., 2019, P13-2 Prevalence of recurrent Extended Spectrum Beta-Lactamase (ESBL) urinary tract infections (UTIs) in patients within a Urology service and introducing the concept of Faecal Microbiota Transplantation (FMT) as a treatment modality, British Association of Urological Surgeons Annual Scientific Meeting, Publisher: SAGE Publications, Pages: 83-85, ISSN: 2051-4158
Ming DK, Otter JA, Ghani R, et al., 2019, Clinical risk stratification and antibiotic management of NDM and OXA-48 carbapenemase-producing Enterobacteriaceae bloodstream infections in the UK, Journal of Hospital Infection, Vol: 102, Pages: 95-97, ISSN: 0195-6701
Ghani R, Gan C, Mullish B, et al., 2019, MP71-15 Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., AUA 2019, Publisher: Elsevier, ISSN: 0022-5347
Ghani R, Gan C, Mullish B, et al., 2019, Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., Journal of Clinical Urology
Mullish BH, Ghani R, McDonald J, et al., 2019, Faecal microbiota transplant for eradication of multidrug-resistant Enterobacteriaceae: a lesson in applying best practice? Re: 'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: A Randomized Clinical Trial', Clinical Microbiology and Infection, Vol: 25, Pages: 912-913, ISSN: 1198-743X
Ghani R, 2019, 27: Skin and Soft Tissue Infections, Tutorial Topics in Infection for the Combined Infection Training Programme, Publisher: Oxford University Press, USA, ISBN: 9780198801740
Tutorial Topics in Infection for the Combined Infection Training Programme is the first book covering the complete CIT curriculum.
Ghani R, 2019, 28: Bone and Joint Infections, Tutorial Topics in Infection for the Combined Infection Training Programme, Publisher: Oxford University Press, USA, ISBN: 9780198801740
Tutorial Topics in Infection for the Combined Infection Training Programme is the first book covering the complete CIT curriculum.
Jewell P, Dixon L, Singanayagam A, et al., 2019, Severe disseminated infection with emerging lineage of methicillin-sensitive Staphylococcus aureus, Emerging Infectious Diseases, Vol: 25, Pages: 187-187
Ghani R, Gan C, Mullish B, et al., 2018, Prevalence of recurrent extended-spectrum beta-lactamase (ESBL) urinary tract infections (UTIs) in patients within a urology service. Introducing the concept of Faecal Microbiota transplantation (FMT) as a treatment modality., Annual EAU Congress, Publisher: Elsevier, Pages: e375-e376, ISSN: 1569-9056
Ghani R, Mookerjee S, Mullish BH, et al., 2018, Impact on Length of Stay and Antibiotic Use in Allogenic and Autologous Stem Cell Transplant Patients Colonized with Carbapenemase-producing Enterobacteriaceae, IDWeek, Publisher: Oxford University Press, ISSN: 2328-8957
Janmohamed A, Abbara A, Ghani R, et al., 2018, Pneumomediastinum complicating adult-onset measles, CLINICAL MEDICINE, Vol: 18, Pages: 403-405, ISSN: 1470-2118
Abbara A, Chitty S, Roe JK, et al., 2017, Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB centre in the UK, BMC INFECTIOUS DISEASES, Vol: 17, ISSN: 1471-2334
Avery K, Abbara A, Ghani R, et al., 2015, Recurrent tuberculosis at a large tuberculosis centre in the UK, JOURNAL OF INFECTION, Vol: 70, Pages: 427-429, ISSN: 0163-4453
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Chitty S, Ghani R, Abbara A, et al., 2014, P190 Drug Induced Liver Injury In The Treatment Of Tuberculosis In A Busy Uk Centre (vol 69, pg A159, 2014), THORAX, Vol: 69, Pages: 301-301, ISSN: 0040-6376
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