Resistant Infections in Hospitals

[Deetee]

Just a few additions to the excellent info on this thread:

By antimicrobial resistance, most people think that the bug will not respond to the antibiotic. However there is seldom an all-or nothing response, and a number of bacteria develop resistance at a low/intermediate level where they will still respond to antibiotics if the dose is high enough.

Also, some antibiotics will never work in certain bacteria - they do not posess the requisite metabolic pathways to be affected by the drug - one might term this an inherent form of "resistance".

Resistance within a single organism genus can be fiendishly complex.
Take enterococci for example:
Methods for exchanging genetic information (ie DNA exchange) includes the following:
1. Pheromone-responsive plasmid transfer between enterococci - this happens at high frequency and affects other enterococci of the same species.
2. Plasmids can be involved that can transfer DNA among a broad range of other bacterial species and genera, but at a low frequency (IE cross species barrier plasmid transfer).
3. Conjugative transposition involves transfer of specialized transposons at low frequency but to a very broad range of different kinds of bacteria, also generating cross species barrier transfer of resistance. Conjugative transposons are relatively nonselective and are one of the few types of elements known to have crossed the Gram positive/Gram negative barrier.

In addition, enterococci have the following little tricks up their sleeves:

Beta lactam resistance. Other streptococci usually respond to beta-lactam antibiotics (penicillin derivatives, cefalosporins etc), but enterococci seem to be able to produce beta lactamase enzyme as an intrinsic property, rendering them less sensitive to these drugs.

They also produce penicillinase, and have another penicillin group defense in that they have a cell wall synthesis enzyme that is relatively resistant to inhibition by penicillin. This low-affinity penicillin binding protein (PBP) is called PBP5. Altered expression of PBP5 results in differing levels of resistance.

Enterococci possess a low level resistance to aminoglycosides (eg gentamicin, streptomicin), but in combination with other antibiotics like penicillin there is a beneficial synergistic bacteriocidal effect (not quite sure why this is I'm afraid). However, enterococci can develop a high level aminoglycoside resistance pattern, usually due to development of phosphotransferase enzyme activity. You have this - tough.

Often, with a very resistant enterococcus, you have to wheel out your last line of attack - glycopeptide drugs. But wait..... Of great concern ids the development of glycopeptide resistance (eg vancomycin) due to the presence of a cluster of chromosomal genes (vanC and vanT genes).

On an interesting aside, these genes if transfered to MRSA (resistant staphylococci) result in the nightmare scenario of MRSA which may not even respond to glycopeptides, the mainstay of our armament against MRSA. This used to be called VISA (vancomycin Intermediate-resistant Staph aureus), but apparently representation from Barclaycard to change the acronym has been successful, and we may not be allowed to call them that anymore and we have to call it VRSA

 

[Badly Shaved Monkey]

Thanks deetee. Do you have anything to add on the stability of resistance if the population is no longer exposed to that antibiotic?

 

[Mojo]

Resistance can wane in the absence of the antibiotic but usually only very slowly. Some plasmids carrying resistance genes aren't very stable.

Recently this wane in resistance has been important medically.

It's not going to be entirely to do with the stability of the plasmid. Genes for resistance are going to carry some sort of cost. Even if it's not particularly great, surely any cost at all is going to lead, in the long-term absence of the antibiotic, to resistant strains being out-competed by their non-resistant counterparts.

 

[Deetee]

Thanks deetee. Do you have anything to add on the stability of resistance if the population is no longer exposed to that antibiotic?

For bacteria I imagine there is a degree of resistance persistence, but I imagine there is a cost in maintaining this. In the field closest to my heart (HIV) one can see this with resistant strains of virus. Once selection pressure is removed, the "resistant" phenotype/genotype becomes a minority population very quickly - this is because viruses that have been selected for are usually affected in other ways - less replicative capacity usually.
Nevertheless, after considerable periods of drug-pressure free time (many months), when re-introduced to the drug, resistant strains are picked up very quickly on testing, suggesting that they have been lurking in the background all along. Mojo has it to rights.

Things will be different for bacteria of course, since they have less ability to survive long periods of relative "dormancy", so perhaps any selected resistance will disappear quicker. In practice, this seems to be the case for most organisms, but again I would not be too dogmatic about this, since carriers of MRSA can persist in carriage for many months even without drug pressure.