Dr Brad Spiller

Publication

• Date
• Type
• Promoted

Research

Revolutionary New Legionella media patented

In collaboration with Dr. Vicky Chalker at Public Health England, the Spiller laboratory has patented a new solid Legionella medium (Legionella Antimicrobial Susceptibility And Resistance Universal Screening medium: LASARUS) that replaces activated charcoal-containing medium. The new medium is transparent and does not absorb antimicrobials like all traditional solid agar.    Two publications will shortly be available from the Journal of Antimicrobial Chemotherapeutics: 1) the systematic investigation showing superiority of LASARUS to traditional Buffered Charcoal Yeast Extract (BCYE) agar and complete concordance between broth microdilution (gold standard method) and LASARUS for antimicrobial susceptibility testing. 2) Viewpoint authored by the Centers for Disease Control and members of the EUCAST steering group and the leads for most international Legionella Reference laboratories calling for cease in using BCYE for resistance screening and recommending it's replacement with LASARUS for methods requiring solid agar.

Sexual Health Patient Research

There are currently 3 separate KESS2-funded active research projects:

1. In collaboration with industrial partner Health First Consulting, to evaluate the specificity, sensitivity and AMR accuracy of the CPM SAS (Italy) MYCO WELL D-ONE assay on 1000 Welsh patients attending walk-in Sexual Health NHS clinics in Rhondda Cynon Taf. Collection of these samples has concluded as of October 2018. A follow-on IRAS ethics has now been obtained to correlate specific sexual health diagnoses to presence (as well as bacterial load thresholds) for Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium infection.  These studies were also able to incorporate development of a new parC -mutation diagnostic assay from SpeeDx, which will shortly be published. (MPhil student Daniel Morris, Medical student Christopher Rees)
2. In collaboration with industrial partner, Cwm Taf University Health Trust, to evaluate the specificity, sensitivity and AMR accuracy of the CPM SAS (Italy) UROGEN WELL D-ONE assay and the BioMerieiux (France) prototype for Mycoplasma IST3 assay on 500 symptomatic sexual health patients attending walk-in sexual health clinics at Keir Hardie Health park and St David's Hospital. Similar to the previous study, however this chromogenic culture diagnostic assay extends to Neisseria spp., E. coli, Group B Streptococcus, Candida, Trichomonas vaginalis, Gardnerella vaginalis, Staphylococcus and Enterococcus spp. Multifactorial and odds ratio associations for each microbe will be determined for urethritis, cervicitis, pelvic inflammatory disease and other relevant sexual health maladies. This study will continue recruiting until September 2019.   (MPhil student Andrew Barratt/technical assistance Ian Boostrom)
3. In collaboration with industrial partners Public Health Wales and Cwm Taf University Health Trust, an interventional clinical trial (THE ANTIBIOTIC GUARDIAN study) will determine the benefits of rapid targeted therapeutic intervention on the rate of clinical symptom resolution for patients and number of clinical visits to sexual health clinics. This project is also designed to reduce the amount of incorrect antimicrobial prescription and determine effective working antibiotic guardian guidelines without diminishing patient care. (PhD student Martin Sharratt, Nurse Rebecca Davis)

Legionella pneumophila research

Legionella pneumophila is a remarkably fastidious bacteria and it's requirement for addition of activated charcoal to agar-based culture has long interfered with the capacity to determine antimicrobial susceptibility testing.  Activated charcoal not only makes it difficult to visualise the growth of bacteria on the plate (requiring evaluation of the plate surface with removal of the lid putting the investigator at risk of aerosol exposure to a potent respiratory pathogen), but it also absorbs the antimicrobials to varying extents making it impossible to define an accurate AST or determine AMR. While microbroth dilution methods are available, they are extremely tedious and require evaluation of turbidity on multiple 96-well plates.    We have created a translucent solid culture medium (LASARUS – patent pending), that we have combined with automated multi-pin-inoculation and have currently determined the MIC for 8 antimicrobials on all archived clinical isolates submitted to Public Health England and Wales since 2003 (approximately 2000 isolates) as well as an additional 1000 environmental isolates from PHE Porton Downs.  An important advance as the previous record for AST determination for Legionella pneumophila was 122 isolates!  We are now adapting our high throughput platform to Determine biocide efficacy and to evaluate a series of new antimicrobials/decontaminants. (PhD student Edward Portal)

Streptococcus agalactiae research

We have finished comparing whole genome sequences for 195 blood isolated strains collected between 2014-2015 (in collaboration with Public Health England and supported by the Fiona Elizabeth Agnew Trust) relative to AST determination to correlate all the available antimicrobial resistance and virulence genes to patient outcome. The results of these studies will be presented at the FEMS meeting in Glasgow July 2019.    The research programme is now expanding to compare UK isolate genomes to all invasive blood and CSF isolates from Sao Paolo Brazil (collaboration with Diego Andrey – Switzerland and Ana Gales – Brazil) and strains collected during routine antenatal screening in Perth Australia.  (PhD student Uzma Basit Khan).

Molecular manipulation of Ureaplasma parvum

Although commonly dismissed as a commensal, there is no escaping the dominant association of Ureaplasma infection and preterm birth – or at a minimum the key role of Ureaplasma respiratory infection of preterm infants and the development of chronic lung disease.  Routine clinical evaluation of preterm neonates at the Children's Hospital at University Hospital of Wales has determined that successful transfer from invasive mechanical ventilator assisted breathing to non-invasive continuous positive airway pressure – assisted breathing requires successful treatment of underlying Ureaplasma spp. infections. This is particularly difficult as all Ureaplasma spp. are inherently resistant to all antimicrobials except for tetracyclines, fluoroquinolones and macrolides. The first two of which cannot be used in children due to adverse effects on teeth/bones and tendons/ligaments respectively. Not all strains are pathogenic and respectively. Not all strains are pathogenic and respectively.       there is a void in the information regarding the mechanisms of pathogenicity or identification of virulence genes for this organism as they are one of the smallest (200-500 nm) and most difficult to culture.  Following on from our previous unique success as the only laboratory to successfully achieve random insertion mutagenesis inactivation of genes, we have now delivered luciferase genes that allow visualisation of these organisms following engulfment my leukocytes and in vivo tracking of infection in experimental models.

Biography

Originally a Canadian Microbiologist from Vancouver, I initially came to the U.K. to examine innate immune evasion of microbes. From 2000 to 2005 I established an independed research group through the Wellcome Trust Career Development Fellowship Program, before joining the Department of Child Health at University Hosptial of Wales in 2005 to develop a new research theme examining antimicrobial resistance in bacterial infections of premature neonates.  This led to my establishing the leading U.K. reference laboratory for investigations of Mycoplasma and Ureaplasma infections. These cell wall-less bacteria are inherently resistant to most antimicrobials and are the leading cause of preterm birth and are emerging as respiratory pathogens.  I am in my third elected term as the Secretary-General of the International Organisation of Mycoplasmology (http://iom-online.org).

In 2012, I began a Royal Society funded collaboration with the University of Western Australia to investigate intrauterine microbial pathology and develop new antibiotics that were safe and effective for use in pregnant women.  These collaborations resulted in my being awarded an adjunct Assistant Professorship at the University of Western Australia's School of Women's and Infant's Health, Perth, Australia in 2014. The success of the Cardiff-Australia collaborations led to a promotion to Associate Professor in 2021.

Also in 2015, I joined the All Wales Antimicrobial Resistance Research unit, headed by Prof. Timothy Walsh, and have been expanding my research of antimicrobial resistance to other bacteria.  As a result in 2017, I have new research projects characterising Group B Streptococcus strains isolated from U.K. sepsis patients and characterisation of Legionella pnuemophilia isolates from U.K. outbreaks of Legionnaires' disease, also known as legionellosis.  In 2020, Prof. Walsh left for the University of Oxford and I was appointed as Head of Medical Microbiology.  Currently I am leading a consortium to unify the Antimicrobial Resistance Testing for Legionella, as supported by the ESCMID Study Group for Legionella Infections executive committee as well as setting up new research hubs in Ghana and Uganda to study prevalence of Antimicrobial Resistance in 2021.

Education and qualifications:

1995: PhD (Pathology), University of British Columbia, Vancouver, B.C. Canada

Honours and awards

• 2000 Wellcome Trust Research Career Development Fellowship
• 2015 Awarded Honorary Adjunct Assistant Professorship at the University of Western Australia
• 2020 Awarded the Derrick Edward Award for contribution to the field of Mycoplasmology by the International Organisation of Mycoplasmology
• 2020 Awarded Honorary contract for Consulting Microbiologist with Public Health England
• 2021 Promoted to Honorary Adjunct Associate Professorship at the Universtiy of Western Australia

Supervisions

Current supervision

Mr Martin Sharratt

Research student

Mrs Jawaria Aziz

Research student

Miss Leanne Davies

Research student

Mr Jordan Mathias

Research student

Mr Ian Boostrom

Research student

Past projects

Apr. 2023-Apr. 2024   Leanne Davies  (primary supervisor for M.Phil in Med Micro)  “Evaluation of media for the susceptibility testing of N. gonorrhoeae.”

Jan. 2023-Jan. 2027   Jawaria Aziz (primary supervisor for Ph.D. in Med Micro)  “The burden of Coagulase-negative Staphylococci antimicrobial resistance in neonatal sepsis in the LMIC”

Jan. 2023-Jan. 2027   Jordan Mathias (primary supervisor for Ph.D. in Med Micro)  “The burden of Staphylococcus aureus antimicrobial resistance in neonatal sepsis in the LMIC”

Jul. 2021-Jul. 2025     Ian Boostrom (primary supervisor for Ph.D. in Med Micro)  “Improving detection of Legionella species from environmental and clinical sources)”

Sep. 2019-Sep. 2023   Martin Sharratt (primary supervisor for Ph.D. in Med Micro)  “The Antibiotic Guardian Study (targeted therapeutics based on rapid diagnostics)”

Sep. 2018-Sep. 2021   Mei Li (replacement supervisor for Ph.D. in Med Micro)  “Assessment of global impact of mcr-1/mcr-3 mediated colistin resistance” Successfully defended

Jan. 2018-Jan. 2021   Katy Thomson (replacement supervisor for Ph.D. in Med Micro)  “Assessment of antibiotic resistance in pathogens causing neonatal sepsis, associated mortality and recommended treatment options in low- and middle- income countries” Successfully defended 16/12/2022

Sep. 2017-Sep. 2021   Dr. Edward Portal  (primary supervisor for Ph.D. in Med Micro)  “Phylogenetics, sequence-type characterisation and persistence of Legionella pneumophila in patients and the environment” Successfully defended 23/02/2022

Sep. 2017-Sep. 2021   Dr. Uzma Basit Khan  (primary supervisor for Ph.D. in Med Micro)  “Detailed genomic and antimicrobial resistance comparison of UK Streptococcus agalactiae isolates from adults to those of diverse global origins” Successfully defended 22/02/2021

Sep. 2014-Sep. 2018   Dr. Qui Yang  (co-supervisor for Ph.D. in Med Micro)  “Multifaceted aspects of MCR-mediated colistin resistance: Fitness, virulence, environmental reservoirs and genomic insights” Successfully defended 02/10/201513/08/2018

Oct. 2017-Sep. 2019   Mr. Daniel Morris  (primary supervisor for MPhil. in Med Micro)  “MYCO WELL D-ONE: Can a new rapid diagnostic test for Ureaplasma and Mycoplasma detect infections” Successfully defended 19/07/2019

Sep. 2012-Sep. 2015   Dr. Shatha Ahmed  (primary supervisor for Ph.D. in Child Health)  “Antigenic Ureaplasma variation and adaptation to in vivo and in vitro immune pressure” Successfully defended 02/10/2015

Oct. 2012-Oct. 2015   Miss. Rebecca Brown  (primary supervisor for Ph.D. in Child Health)  “Determining Mycoplasma susceptibility to and evasion from the innate immune system” Successfully defended 16/06/2016.

Jan. 2011-Jan. 2015   Mrs. Amina Bshina  (primary supervisor for Ph.D. in Child Health)  “Intracellular and cell-surface Neutrophil proteinase levels and distribution: changes following extravasation and microbial infection” Successfully defended 05/02/2015

Jan. 2010-Jan. 2014   Mr. Ali Aboklaish (primary supervisor for Ph.D. in Child Health)  “Determining the Immunodominant antigens from Ureaplasma parvum and their stability under immunological pressure” Successfully defended 01/12/2014.

Oct. 2009-Oct. 2010   Dr. Salima Abdulla (primary supervisor for M.D. in Child Health)  “Developmental Innate Immunodeficiency: Comparison of Term Neonatal Neutrophil Proteinase and Complement component levels relative to Adults” Successfully defended 07/12/2012

Oct. 2006-Oct. 2009   Mr. Michael Beeton (primary supervisor for Ph.D. in Child Health)  “Mechanism of Macrolide (antibiotic) resistance of Ureaplasma isolated from Newborn Preterm Infants.” Successfully defended 31/03/2010.

Mar. 2006-Mar. 2007 Dr. Phil Davies (co-supervisor for M.D. in Child Health)  “Presence and pharmaceutical administration of alpha-1-anti-trypsin in paediatric lung disease and cystic fibrosis.”  Successfully defended 25 June 2008.