Authors: John P. Hays (Erasmus MC, Rotterdam, The Netherlands)
Take a look behind the scenes of a recent Future Microbiology paper entitled: ‘Challenges in identifying antibiotic resistance targets for point-of-care diagnostics in general practice’, as we ask author John P. Hays (Erasmus MC, Rotterdam, The Netherlands) about detecting antibiotic resistance and the hurdles this field faces.
What inspired you to write this special report?
The authors are partners in an European Union H2020-funded project ‘DIAGORAS;’ (www.diagoras.eu), which aims to develop a rapid infectious disease diagnostic device for use by family doctors and dentists. The project aims to diagnose oral and respiratory tract infections (RTIs) using a fully integrated, automated and user friendly platform for physicians’ offices, schools, elderly care units, community settings etc. RTIs (e.g., tonsillitis, pharyngitis, rhinitis, sinusitis) will be diagnosed by means of DNA/RNA amplification. Oral diseases (periodontitis, caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalized monitoring.
What are the main problems with the current ‘gold standard’ antibiotic resistance detection strategies?
Current ‘gold standard’ antibiotic resistance detection strategies tend to be slow, requiring the microorganism to be first isolated by culture. The cultured microorganism is then grown in the presence of antibiotics to determine its sensitivity/resistance profile. This process can take 24 – 48 hours (or longer). During this time clinicians frequently prescribe ‘broad spectrum’ antibiotics that tend to have a non-specific effect on the host microbiota (leading to for example diarrhoea) and may lead to the generation of antibiotic resistance in (non-) target microorganisms.
More rapid targeted antibiotic prescribing (when the causative microorganism or antibiotic resistance is known) may reduce the impact of antibiotics on the host microbiota, reduce the chance of antibiotic resistance emerging and could be cheaper. It is also important to remember that the rapid differentiation of a viral from a bacterial infection may limit the amount of unnecessary antibiotics prescribed to patients with viral infections.
What point-of-care (POC) diagnostics are available/ currently being developed?
Lateral flow devices e.g., dipstick tests have been available for some time. Nowadays, several nucleic acid amplification-based or protein-based POC diagnostic devices are available on the market, though a major problem is the actual implementation of these devices into the healthcare setting.
Syndromic-based rather than pathogen-based diagnostic devices are preferred. Syndromic-based diagnostics are more relevant to the needs of a clinician when making a diagnosis for a specific set of symptoms, rather than simply adding many different pathogens to a diagnostic test simply because the technology involved can detect multiple different pathogens.
Future POC trends include the further development of biological diagnostics e.g., isothermal enzymes, synthetic biology etc., and technological innovations e.g., self-powered diagnostics, nanowire diagnostics etc.
What are the key hurdles in developing antibiotic resistance detection panels for use in POC diagnostics?
The development of POC antibiotic resistance panels in hospitals is relatively straight forward, including the detection of MRSA, VRE, ESBL and CRE-resistant microorganisms. However, in the community the types of microorganisms causing infections, and their corresponding antibiotic resistances, may be very different.
Differences in antibiotic resistance are also due to differences in the types of antibiotics prescribed in the community compared with the antibiotics prescribed in hospitals. Most challenging is the detection of antibiotic resistances related to the loss of bacterial porins and/or increases in bacterial efflux pump activity.
If you could change any legislations/ guidelines in your field, what would they be?
As members of the international Joint Programming Initiative on Antimicrobial Resistance – Rapid Diagnostic Testing (JPIAMR AMR-RDT) group, some of the authors are already involved in publishing guidelines/roadmaps for ‘Behaviour Change’, ‘Target Product Profiles’ and ‘Antimicrobial Susceptibility Systems’. These publications will be available soon.
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- A peek behind the paper – Shilian Xu on the dominance of different bacterial genotypes under sublethal antibiotic pressure