Antimicrobial Resistance Testing: From the lab to the patient.

Question: What do the following have in common?

Antibiotic Dose

Tissue Penetration

Site of Infection

Patient Immunity

Pharmacokinetics of drug in patient

Extent of Infection

Wrong pathogen isolated

Polymicrobial Infection

 

……and probably many more.

 

Yes, these are all factors which dictate why even though a lab says a bacterium is resistant to an antimicrobial, the patient nevertheless gets better on that antimicrobial, and vice versa.

 

We are entering the murky world of in-vitro versus in-vivo response.

 

I often get queries from GPs wondering why MRSA infections improve on Flucloxacillin, etc etc. “How can this happen?”

 

The reasons are above. In the pre-antibiotic era, lots of people, particularly with minor soft tissue infections, got better without the help of antimicrobials.

 

Because of the myriad of different factors involved, I cannot see in-vitro susceptibility testing ever being anything more than a “best guess” at clinical response. For this reason alone, it actually makes me wonder whether we may overdo susceptibility testing and whether it should be more often reserved for the more serious infections.

 

 

MIC Breakpoints.

 

In-vitro susceptibility testing is based on MIC (minimum inhibitory concentration) breakpoints. Above a certain breakpoint, the bacterium is deemed resistant to the antimicrobial, and vice versa.

The MIC breakpoint is set using an ill-defined mix of epidemiological, pharmacokinetic and occasionally, clinical data.

 

To make matters worse, there are different organisations involved with setting standards for laboratory antimicrobial susceptibility testing. Sometimes these organisations struggle to agree on the MIC Breakpoints for different organism/antimicrobial combinations. For example look up Cefipime breakpoints for E. coli in both the CLSI and EUCAST guidelines. (What must the clinicians think of us!)

 

What is important to note however is that giving an MIC is better than just calling an organism susceptible or resistant. At least with an MIC value you can get an idea of the degree of in-vitro resistance or susceptibility. If the antibiotic is just reported as susceptible or resistant, then it gives the clinician no idea of how close it is to the breakpoint (from an in-vitro point of view).

 

I think the debate around in-vitro testing and in-vivo response will continue unabated for the rest of my lifetime…

 

Michael