F ast-moving changes in the
field of infectious diseases have resulted in a situation that is very different
to that seen a decade ago. If the pace of these changes continues, which appears
likely, we can only conjecture what the next decade will bring. Professor Ethan
Rubinstein is a world-recognized expert in the field of infectious diseases and
is one of the most qualified people to comment on these past changes and on likely
new developments. Prof. Rubinstein, in an interview by Penetration, provided
an overview of where we were ten years ago, where we are now, and where we are
likely to be ten years hence in regard to infectious diseases.
Turning his attention to the past, Dr. Rubinstein described developments as
essentially positive and negative. Among the positive developments, there has
been a tremendous jump forward in the availability of antibacterial and antiviral
compounds. Fluoroquinolones have progressed to second- and third-generation agents
that have enhanced activity against respiratory pathogens as well as improved
safety profiles for some. Dr. Rubinstein described the advent of the new antivirals,
particularly those with activity against influenza, as one of the most significant
achievements of the last century. In addition, a number of cytokines have been
introduced into clinical practice, although in a relatively limited fashion.
There have also been immense achievements in diagnosis, principally due to
an explosion in molecular biology. This allows the clinician to diagnose pathogens
earlier and in a more precise manner, which will certainly translate into improved
therapeutic strategies. Another development has been improved understanding of
the relationship between chronic disease and pathogens for which the etiology
was previously unknown. For example, Crohn´s disease is today associated
with a Mycobacteria pseudotuberculosis, atherosclerosis has been linked
with Chlamydia pneumoniae, and asthma has links with cytomegalovirus. By
understanding the etiology of such chronic diseases, future treatment, while difficult,
is likely to be improved.
Unfortunately, the last decade has also seen some negative changes. Dr. Rubinstein
described the unwelcome developments of the presence of vancomycin-resistant Gram-positive
bacteria, particularly enterococci and staphylococci, both in Japan and the United
States. Another problem has been the spread of Gram-negative pathogens capable
of producing extended spectrum ß-lactamase, making them resistant to many,
if not most, ß-lactams. There have also been outbreaks of unexpected diseases
such as Hanta fever, West Nile fever, and Avian flu as well as outbreaks of food-
or water-borne diseases such as those caused by Escherichia coli or 157
The last ten years have also been marked by changes in the pattern of disease.
For example, the prevalence of tuberculosis has increased, worsened by the presence
of many multidrug-resistant pathogens. Previously well-controlled diseases are
now out of control, exemplified by outbreaks caused by penicillin- and macrolide-resistant
pneumococci that are threatening the health of children and adults alike. Another
problem on the verge of escalating is meningococcal diseases that are resistant
to antibiotics and are not covered by vaccines. The problem of vaccine coverage
also relates to the pneumococci. Ten years ago the vaccine covered a large majority
of pneumococcal strains, but now the number of strains causing infection that
are not covered by the vaccine is increasing.
Dr. Rubinstein believes that developments likely to occur in the next ten
years could also be classified as positive or negative. Positive changes include
continuing improvements in molecular biology that are sure to have a significant
impact on diagnosis. Information from the genome project, relating not only to
humans but also eukaryotic cells and bacteria, will contribute tremendously to
the pharmaceutical industry. This contribution will be in the form of drug development,
definition of new targets, and greater understanding of the interaction between
bacteria and man. Thus, new drugs will be developed to treat diseases that have
no therapy today. These include examples such as antibiotics to treat vancomycin-resistant
Gram-positive organisms as well as Gram-negative bacteria. There will be new antibiotics
for children, and safer compounds will continue to be developed. Fluoroquinolones
will continue to advance, with a focus on respiratory pathogens and enhanced safety.
It is also likely that within the next decade there will be fluoroquinolones that
can be used in the pediatric setting.
Clarification into the etiology of chronic diseases will continue, resulting
in both chemotherapy and vaccines aimed at treating these conditions. Dr. Rubinstein
also believes that there will be more of a connection between some cancers and
microbiology. This will be of particular relevance for colon and cervical cancers,
where it is likely a virus or microbe will be implicated in their pathogenesis.
These developments will also lead to improved treatment strategies, and can only
be described as positive changes.
The negative threats are numerous. Dr. Rubinstein believes that pneumococci
resistant to vancomycin will be seen in the community and that vancomycin-resistant
staphylococci will be very common, as will strains of bacteria resistant to all
antibiotics. Agricultural and farming use of antibiotics may create serious problems
and is an area that should be looked at closely. New bacteria and viruses will
be defined, and antigenic shift of viruses will result in previously safe viruses
becoming pathogenic. Adaptation of animal viruses into humans and vice versa is
also a possibility. However, on a positive note, Dr. Rubinstein thinks that there
will be more means to diagnose and combat these adaptations.
As we enter the new century, infectious disease treatment stands at the threshold
of immense possibilities, both good and bad. Dr. Rubinstein concluded that it
is the responsibility of all physicians, researchers, and patients alike, to ensure
that positive developments are pursued actively and that everything possible is
done to hinder the development of negative changes. In this way, the health of
all mankind can and will continue to improve.