AUTHOR=Moore John E. , McCaughan John , Rendall Jacqueline C. , Millar Beverley C. 

TITLE=Case Report: The Conundrum of What to Pick? Antibiotic Susceptibility Variability in Burkholderia cenocepacia in Cystic Fibrosis: Implications for Antibiotic Susceptibility Testing and Treatment

JOURNAL=British Journal of Biomedical Science

VOLUME=Volume 81 - 2024

YEAR=2024

URL=https://www.frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2024.12749

DOI=10.3389/bjbs.2024.12749

ISSN=2474-0896

ABSTRACT=Within cystic fibrosis (CF) microbiology, there is often mismatch between the antibiotic susceptibility (AS) result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive.AS to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates (n=11) from an adult CF patient, over a 63 month period.Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with CLSI methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole (R,R, I, I). Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II & III) preceding this complete resistotype. The bacterium continued to display further AS heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V -XI). The Relative Resistance Index (RRI) of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such requirement for large numbers of colony picks combined with AS-related methodological problems creates a conundrum in biomedical science in providing a robust assay that will capture AS variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in AS testing with Burkholderia cenocepacia. Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their CF patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.