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 cryptosporidium.

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.