“Molecular diagnosis of wound infections: The Holy Grail.”

The slice of pie taken by the molecular department in the microbiology laboratory is increasing, slowly but surely.

On the contrary, the proportion of culture based microbiology is inexorably declining.

Many clinical microbiology laboratories are now switching, or looking at switching over to molecular diagnosis of enteric pathogens.

Molecular diagnosis of pathogens causing vaginitis and pharyngitis will not be far behind, and a few labs have already moved in this direction.

However diagnosis of wound infections remains firmly culture based. There is not even much in the literature with regards to molecular diagnosis of wound infections…

Is it even possible?

So what are the difficulties?:

  • Potential number of pathogens: There are several pathogens or putative pathogens that are able to cause wound infections. This makes PCR based molecular diagnosis more difficult. However, on the flip side, 95% of wound infections in a general clinical setting are caused by two pathogens, Staphylococcus aureus and Streptococcus pyogenes (Group A streptococcus).
  • Lack of susceptibility information: Molecular diagnosis of resistance determinants is still a little behind phenotypic culture based testing. However with regards to the two main pathogens as above, PCR analysis can easily differentiate between MSSA and MRSA, and susceptibility data for Streptococcus pyogenes is only required for a small proportion of patients who have anaphylactic reactions to penicillin.
  • “Over-sensitivity”: It is always nice to know which are the dominant organisms within a wound. Culture is relatively good at this. However molecular methods are starting to be able to quantify to some extent (e.g by playing with the cycle threshold cut-off).
  • Cost: The culture of a standard wound swab might cost $10 or so, even when overheads are included. In my experience molecular tests have to be performed in very large volumes to even get close to this kind of price. However wound swabs do arrive into the laboratory in very large volumes!

If it was easy it would have been done by now… I suspect it is the 4 things above acting together as a “bundle”, as opposed to any one insurmountable barrier which has contributed to the lack of progress up until now.

However it will come in some form or other, you can be sure of that…

Here is a potential solution I have thought of:

  • Any wound swab accompanied with clinical details suggesting an unusual pathogen e.g. animal bites (Pasteurella), water exposure (vibrios, aeromonas), immunocompromise,  would still undergo routine “catch-all” bacterial culture.
  • The rest (the vast majority) would be subjected to a multiplex PCR for the detection of MSSA, MRSA and Streptococcus pyogenes (and possibly Group G streptococcus also). A positive result would be reported routinely. A  negative result would have an accompanying comment to suggest contacting the laboratory if the patient’s symptoms were persisting, or if further susceptibilities are required, so that culture could be set up if necessary.

In this way molecular diagnostics could be performed on (a good proportion of) wound swabs at a relatively low cost.

In addition multiplex PCRs could be developed specifically for infections in specific clinical situations, e.g. post animal bite,  etc., etc.

Automated bacteriology culture systems like Kiestra TLA would not have happened if the industry didn’t think that there was at least another 20 years or so of culture based bacteriology left, and they are probably right. But I don’t think it will be too long before commercial laboratory diagnostics companies start looking closely at “wholesale” molecular options as above.

And who knows, whole genome sequencing might come in and completely disrupt PCR based molecular diagnostics, and the picture might change again…

The future’s uncertain and the end is alway near


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