Antimicrobial Usage & Spread of Resistance -Reply -Reply

Steven Projan PROJANS at war.wyeth.com
Thu Jan 23 07:57:36 EST 1997

In response to my posting on antibiotic resistance Matthew L. Nilles
writes (in part):

"Prolonged exposure of bacteria to antimicrobial agents can and does
select for resistant bacteria.  Growth of E. coli for extended
generations in the presence of chloramphenicol or tetracycline
selects for Multiple
Antibiotic Resistant (Mar) strains of E. coli (extensively
demonstrated in the basic literature).  These strains are not only
resistant to tet and cam but are also resistant to flouroquinolones
and beta-lactams (and many other compounds).  This same effect is
acheived by exposure to environmental phenolics and oxidative stress
(i.e. Nitric oxide), again this is all documented quite well.  The
regulatory genetic loci responsible (such as marA and soxRS) are
found in diverse gram negative bacteria.  The efflux pump systems
responsible for most of the induced resistance are also found in
diverse bacteria (i.e. E. coli, Salmonella,
Neisseria, Haemophilus, Pseudomonas, etc.)"

This is quite true and represents the work David White and Stuart
Levy.  The only problem is, that outside of Pseudomonas, MAR
mutations have not been shown to have much (if any) clinical
significance - example: almost all tetracycline resistant strains
found clinically carry acquired resistance genes (and not found to
carry MAR mutations).  The same thing is true for most bacterial
strains resistant chloramphenicol, erythromycin, penicillins,

The mar story probably tells more about bacterial physiology and
bacterial adaptation to environment than it does about the
acquisition and spread of antibiotic resistance.

And just to remind Matthew Nilles to read the data - Levy's worked
required "Prolonged" continuous exposure, in the lab, over many more
generations of bacterial growth than are inivolved during a patient's
treatment.  Another point about mar - Levy found that salicylic acid
(found in aspirin) also selects for mar mutants!!!!  Should we stop
using aspirin (and other NSAIDS) because it may select for antibiotic
resistance???  If you are out there Dr. Levy what do you think?

We all should be aware that it is, indeed, the use of antibiotics
that selects for resistant strains - select for them and they will
come.  However, no one has come forward with data that the
prescription of antibiotics for what may be viral infections has any
real impact on the acquisition and spread of antibiotic resistance.  


Obnoxius as ever,

Steve Projan
Wyeth-Ayerst Research

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