At present, routine anti-microbial susceptibility testing is still dominated by phenotype, with genotypic testing occasionally getting a look in for MDROs.

I doubt this is likely to be the case forever…

As our knowledge of genotypic resistance determinants increases, and the cost continues to decrease, I see a time when first line testing will be the resistance genotype and not the phenotype. I believe this is more likely to be a resistance genotype determined by sequencing as opposed to PCR or other molecular methods.

There will always be some difference between the genotype and phenotype as far as susceptibility results are concerned (Think about the behaviour of identical twins. It’s similar but not identical!). The environment that the bacteria lives in will see to that. However as our understanding of the genotype increases we will be able to more accurately predict the phenotype.

But the correlation will never be perfect. There will still be a role for confirming the phenotype, with phenotypic susceptibility testing indicated in the sick patient who is not responding as expected.

I can see this transition happening within my working lifetime, i.e. within the next 25 years.

However having said all this, it is important to be aware that the genotype is not always the perfect answer, and has its own set of problems (the following is an excerpt from my book, The Art of Clinical Microbiology)…

• Genotypic resistance testing may well be over-calling antimicrobial resistance in some cases, and thus pushing patients unnecessarily towards broader spectrum antibiotics, thus starting a vicious circle of resistance. This is not something however, that is often brought up in the antimicrobial stewardship committee setting.

• Genotypic testing will (currently) miss some resistance that is demonstrated phenotypically and due to multiple combined mechanisms e.g. carbapenem resistance in some Pseudomonas aeruginosa due to hyper-production of AmpC plus porin loss and/or efflux pump.

• Genotypic testing will (currently) only pick up the resistance genes we know about. We need phenotypic methods to detect new resistance as it appears and then use genotypic testing to find the genetic ‘code’ for it.

• Genotypic testing may be over-sensitive when used to screen for MDROs in the setting of Infection Control. This can lead to patient isolation or non-use of an antibiotic because of a positive result, but the burden present or organism carrying the resistance gene(s) does not pose a significant clinical risk to the patient, and possibly no Infection Control rise to the institution.

However I don’t think this will stop the transition from phenotypic to genotypic susceptibility testing happening, when the price is right…

And when this transition does occur that might spell the end for large volume, culture based diagnostic bacteriology…

Michael