Monthly Archives: June 2016

“Defying Nature”

Antimicrobial Resistance, ,

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I occasionally hear people/experts saying that antibiotic resistance can be acquired by bacteria without any cost to the ‘fitness’ of the organism (i.e. it’s ability to replicate and survive in a competitive environment)

I could not disagree more…

If antibiotic resistance could be acquired without any cost to fitness, I think all the human bacteria (as well as all the environmental ones) would be pan-resistant already. It just doesn’t make sense to me.

Bacteria are masters of survival. They are also hyper-efficient, and need to carefully budget their energy quota not only on defence, but also on attack and redeployment, not to mention communication. If the bacterial population does not need to be resistant in a particular environment, it will not waste its precious energy on resistance genes for a “Just in case” scenario.

Most in-vitro studies show that acquisition of antibiotic resistance does indeed have a fitness cost. A few don’t. For those exceptions I would offer the following explanations:

  • Just like anti-microbial susceptibility testing, I suspect that in-vitro bacterial fitness correlates only roughly with in-vivo fitness.
  • The fitness cost may be so miniscule, that it is impossible to demonstrate in the laboratory setting.

So in an antibiotic free environment, the susceptible strain will eventually win out over the resistant one. This might take days, or it might take decades, depending on the relative fitness difference. The fitness gap between susceptible and resistant strains might also be narrowed by compensatory mutations, but it will never be zero. It is all just a matter of time, evolutionary time…

If a bacterium doesn’t need to be resistant, then it won’t be, and it will eventually dispose of the means to be resistant.

Bacteria are lean, mean, replicating machines. They are also highly obedient to the Laws of Evolution…

Michael

For a nice article on the above concept, with a few references attached, click here. About a 5 minute read.

“Selling your soul to the devil”

Confessions of a Microbiologist,

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During the American Society of Microbiology (ASM) conference in Boston, I attended an industry sponsored evening symposium. This was held by a pharmaceutical company promoting a new antibiotic.

A lavish meal was provided in plush surroundings for approximately 300 attendees. It must have cost the company a small fortune… To ASM’s credit, at least it was clear on the program that it was an industry sponsored event.

Three “expert” speakers had been recruited to talk at the seminar, and I am sure they were all handsomely rewarded for their efforts. I am also sure that all their talks were carefully vetted beforehand. The title of the seminar was not “Please use antibiotic X as much as possible“, but rather the more subtly titled “Best practice management for Infection Y in Population Cohort Z“.

You get the picture…

Each speaker declared multiple conflicts of interest, having received consulting fees from several different companies. They were all “distinguished” in the fields of microbiology and Infectious Diseases. A means of extra income I guess, but not the life for me. I prefer to set my own agenda as opposed to having it set for me…

Anyway, I made it through about half of the seminar before my conscience (and jetlag) got the better of me.

I guess the pharmaceutical companies would not hold these costly events if they did not think they were worthwhile.  Maybe we all like to think we are immune to persuasion. However the reality is that most of us, to varying degrees, are not.

And in a sense the pharmaceutical company has achieved their aim. I am now aware of the new antibiotic, and when it becomes available in NZ, I would consider using it if the clinical circumstances justify it.

And I also got my “free” dinner…

Michael

“The end of Clinical Breakpoints as we know them?…””

Future of Microbiology, The Science of Microbiology, , , ,

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During the ASM conference in Boston, I attended a couple of talks on the process of anti-microbial susceptibility testing (AST). There are really only two main players (a duopoly of sorts) left standing with regards to setting standards for AST. These are the Clinical & Laboratory Standards Institute (CLSI) and the EUropean Committee on Anti-microbial Susceptibility Testing (EUCAST).

Representatives from each organisation spoke during the conference sessions. Reading between the lines,  I did not get the impression that a unification of the two organisations was imminent, mainly because I did not detect any warmth between the respective speakers…

There was considerable discussion on the setting of Clinical Breakpoints. Clinical Breakpoints are necessarily a “messy” compromise between Epidemiological Cut-off values (ECOFFs), pharmaco-kinetic & pharmaco-dynamic (PK-PD) data, and most importantly, clinical response. As long as this model continues, EUCAST and CLSI committees will continue to tinker with and argue about the breakpoints, but in the painful knowledge that a single value can never be agreed upon as being a definitive answer. There are just too many variables.

The problem is therefore ripe for an app-based solution…

I foresee a future in anti-microbial susceptibility testing where the main variables are taken much more into account than they currently are.

I see the time when all the microbiology laboratory will do will be to provide an organism identification and  MIC values for a restricted number of key antibiotics.

The clinician will then take his smartphone app, enter this lab information, but also add in key patient variables such as site of infection, renal function & body mass index, and degree of immunocompromise.

The app will then process all these variables together and give for each antibiotic the likelihood of clinical response of a certain antibiotic, not only for this particular organism, but for this particular patient.

And thus there will no longer be a need for concrete/single value clinical breakpoints, but rather the focus will be on personalising the lab information to each particular patient.

I can see such apps for MIC interpretation being developed in the next few years. 

And if I were a lead member of NCCLS or EUCAST I would be recruiting the services of a good IT applications specialist on to the steering committee, and sooner rather than later…

Michael