On Thursday, 1/12/95, Bob Morrell ( bmorrell at isnet.is.wfu.edu) responded to
some of the comments generated by the concerns over how penicillin resistance
developed in S. pyogenes:
"I believe that this concept of a post antibiotic era, an outgrowth of the
infamous Newsweek article considerably overstates the case. Certainly we
are not as far ahead of the bugs as we once were, but a two step lead vs
a ten step lead does not mean the end of an era. Smarter use (actually
reading the lab MIC's would be a start!) will, combined with increased
development, keep us ahead in most infections. (a humble and optimistic
opinion)"
While I agree that "smarter use" of our current antibiotics will slow down our
losing battle with development of resistant organisms, I do not believe it will
give us the protection we need in the very near future. If you look at the
classes of antibitocs available today, most have been around for 20-40 years.
What we have seen is that the 'tweaking' of the basic structure to improve MICs
or activity against one form of resistance (eg. enzyme inactivation) inevitably
leads to the more rapid development of resistance to that 'new' structure. The
genetic pool is out there and so many years of exposure to the basic structure
classes has allowed nature to develop the resistance genes. They are sitting
in the pool 'silently' waiting until they are needed. In essence, the use of
the newer drugs selects for these changes and resistance occurs more rapidly
than the first time a structural class is introduced (when the genetic pool is
'naive').
I think two-steps is more generous than reality. The threat of disease from
resistant organisms is chomping at our heels and we will be outpaced in the not
too distant future. More importantly, this threat is not limited to bacteria
but includes viral and fungal infections as well. The world has changed much in
the last 20 years-travel is easy, can be inexpensive, and an infectious agent
can be transmitted across several continents by a single carrier. Physians may
be slow to recognize the disease because it is not indigenous totheir areas and
as a result, it continues to spread unchecked. It's not just a movie of the week
theme, it's real.
I believe that the only way to ensure our success in this battle is to look for
new targets and completely new structural classes to treat a highly selected
bacterial pool. Unfortunately, this is much more difficult than remodeling a
previous structure and most companies don't want to take the risk on their
investment. The answer is likely to come from smaller companies that look at
niche markets rather than developing the 'super-drug'.
