In this age of do-it-yourself healthcare and the ready availability of wonder drugs that seemingly treat any conceivable disease, many individuals have taken their health into their own hands and forgotten past fears of contracting life-threatening infections. However, it would appear that the use of one class of wonder drug in particular-antibiotics, especially in the form of medicines and soaps-has resurrected many of these once-settled fears as steady numbers of bacterial populations have begun to acquire an effective resistance to some antibiotics. For instance, public concern over the use of antibacterial soaps was first awakened in 1998, when researchers at Tufts University discovered that triclosan-the active ingredient in many antibacterial soaps-functions more like an antibacterial drug than a disinfectant (which should kill microbes, then evaporate away after use) by blocking a specific enzyme that some germs need to survive. Because triclosan doesn't kill bacteria outright, those which do survive exposure to triclosan-which lingers on kitchen counters and other surfaces for days or even weeks-have an opportunity to pass on their acquired resistance to later generations of bacteria, thus contributing to the ineffectiveness of some antibacterial products [1]. In fact, worries over such ineffectiveness were affirmed by the Centers for Disease Control and Prevention as recently as July 2002, when it confirmed the isolation of Staphylococcus aureus bacteria ("golden staph") from a Michigan man that were resistant to the drug vancomycin, considered by many experts as the last line of defense against deadly hospital-acquired staph infections [2].

In an attempt to control the growing onslaught of antibacterial resistance, researchers and public health professionals have made great strides in their respective fields in the development and application of innovative methods and ideas for curbing resistance. Perhaps the most important of these advances has been the shift in approaches toward combating antibiotic resistance itself. One of these paradigm shifts includes the increased use and development of antibiotics which actually kill bacteria-called bactericidal compounds-over drugs which only inhibit their activity or viability, called bacteriostatic drugs [3]. This contrasts with past approaches to the development and use of antibiotics such as penicillin, macrolides, and tetracyclines, which only inhibit a certain aspect of bacterial activity or growth [3].

Another approach to tackling the bacterial drug-resistance dilemma has been to develop mechanisms, which inhibit, or even eliminate, the disease-causing abilities of bacteria-their virulence. This strategy, which was conceived before the 1970's but hasn't been feasible until recently, involves using knowledge of bacterial genomes to synthesize new drugs that specifically target the pathogenic aspects of bacteria. The greatest benefit of this approach stems from the hope that this new class of drugs will not only be safe for use in humans, but will also inhibit the virulence of disease-causing bacteria without actually preferentially killing them. It is hoped that this will make resistance to these new drugs more difficult since the targeted virulent bacteria will potentially face less selective pressures for survival in the presence of these new drugs. As a more temporary response to fighting bacterial drug-resistance, the notion of reintroducing older generation antibiotics has drawn support from some researchers who have seen success in using drugs such as chloramphenicol, which recently has been used to treat severe infections from vancomycin-resistant bacteria [4]. However, this approach is limited by the fact that multi-drug resistant strains of bacteria have begun to appear which, in time, may also add older-generation antibiotics to their resistance arsenal.

Advances in antibiotic resistance research have also produced new methods of drug development that promise to provide some protection against particularly virulent strains of bacteria. For instance, the recent breakthroughs in genomics and DNA analysis have been applied to bacteria in an attempt to understand the mechanisms by which bacteria infect their hosts. Among other things, researchers have targeted and begun to develop compounds designed to attack or exploit specific characteristics of bacteria, such as cell division, cell wall development, and the fragments of DNA, called plasmids, which hold the genes responsible for drug resistance [5,1]. It is hoped that in the near future these tailored drugs will be able to control explosions in the growth and virulence of many pathogenic bacterial populations.

Other drug development strategies involve the study of natural sources of antimicrobial compounds. Insects, for instance, are currently a subject of interest for the discovery of new treatments for infections. For example, scientists from the Entomology Division of Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO) have in recent times successfully isolated and cataloged proteins called antimicrobial peptides from a wide variety of insects which show promise of bacterial growth inhibition in laboratory cultures [6]. Closer to home, researchers from the Wistar Institute in Philadelphia have also found that a peptide called pyrrhocoricin from Pyrrhocoris apterus fireflies is able to kill bacteria by a yet-unknown mechanism [7].

As perhaps the most popular and consistent source of medicines for the treatment of infections, plants have also been intensely studied for their antimicrobial compounds. Small amounts of tea tree oil, for instance, can effectively kill Staphylococcus aureus bacteria, which regularly infect hospital patients [8]. The germ fighting abilities of honey-specifically manuka honey made from the Leptospermum species of plants in Australia-have also fascinated researchers from the University of Wales Institute, Cardiff, who have shown that this particular substance is able to keep badly infected wounds clean, despite the failure of strong antibiotic medications and wound dressings [9].

Considered as the first source of systematically-developed drugs to combat infectious bacteria, chemical design has also proven to be an invaluable tool in current efforts to synthesize new medicines to combat the rise of untreatable infections. Through the use of extensive databases on the chemical structures and functions of existing drugs, researchers have been able to generate newer families of bactericidal compounds, such as oxazolidinones, everninomycin, and ketolides, which offer healthcare providers a more diverse arsenal of drugs to deal with serious infections [1, 3]. The development and distribution of these new families of drugs, however, are only a temporary solution to the drug-resistance problem as a whole since the bactericidal activity of these drugs acts as a selective pressure for bacteria to evolve. In other words, those bacteria which survive their exposure to these substances, have the potential to pass on their resistance to future generations and thus contribute to the development of whole populations of drug-resistant bacteria.

As a more recent initiative that does not involve drug development, government action in the form of legislation has helped somewhat to slow the appearance of newer modes of drug resistance in bacteria. For instance, groups such as the Alliance for the Prudent Use of Antibiotics have been successful in persuading Congress to pass the Preservation of Antibiotics for Human Treatment Act of 2002 and other laws designed to limit the largely unregulated practice of adding antibiotic medication to animal feed [1]. Along these lines, the European Union has taken even more drastic action in a concerted attempt to prevent the influx of residual antibacterial compounds into the human population from farm animals by upholding, last year, a 1998 decision by the EU Council of Ministers to completely ban the use of antibiotics in animal feed [1].

The challenges of a world fraught with life-threatening infectious diseases and the drug-resistant microbes that cause them may not be too far into our immediate future, given the current environment of antibiotic abuse and overuse in certain home and hospital settings. However, there is still hope that the appearance of potentially uncontrollable pathogens may yet be avoided through the cooperation of the scientific community, public officials, and activists, through whom many public health policies are able to effectively reach the public. What has yet to be seen is the wide-spread education of health care providers and their patients against the abuse of antibiotic-containing products, since many still see the often-unnecessary prescription of antibiotic medication as either a cure-all or preventative measure against illness. Truly successful efforts to combat the problem of bacterial drug resistance may perhaps only come from the cooperation of all who are involved with infectious disease: researchers, health care providers, and the public.

Ramil is a second-year student majoring in Biochemistry. Ramil aspires to enter the field of medicine and to provide medical care to underserved communities.