MONTREAL-The emergence of resistant microorganisms is a worldwide threat, Robert C. Moellering, Jr, MD, said at a plenary session of the 19th International Congress of Chemotherapy. While the balance is still on the side of the clinician, he warned that "we are coming perilously close to running out of targets for new antibacterial strategies."
Dr. Moellering, of Deaconess Hospital and Harvard Medical School, and others are sounding the alarm because, "things don't look as bright as they did even a few years ago." No new antibacterials were released last year, he reported, partially because "most of the easy targets that allow selective toxicity have already been discovered" and partially because the process of bringing new drugs to market is extremely expensive.
'Two Curves on a Collision Course'
Dr. Moellering described the decreasing number of effective new antibiotic agents and the rising incidence of resistant organisms as "two curves on a collision course."
He said that resistance has been reported even with some of the newest classes of antibacterial agents, such as the fluoroquinolones and carbapenems, as well as with important drugs, such as vancomycin(Drug information on vancomycin) (Vancocin). Moreover, he noted that resistant strains of gram-positive organisms such as enterococci, staphylococci, Streptococcus pneumoniae, and others represent a rapidly growing clinical challenge.
Current research focused in a number of areas may yield new treatment approaches and/or new antimicrobial agents, Dr. Moellering said. The first approach is a classic one: Screening programs may yet identify antibiotic activity in natural substances that could be the source of new agents.
Molecular chemists are synthesizing future generations of antibiotics by modifying side chains of existing agents, Dr. Moellering said. Vancomycin analogs, for example, are being developed to overcome resistance.
Another major field of antibiotic research concerns development of agents such as the beta-lactamase inhibitors that potentiate the effects of existing antimicrobials. Within this field of study, Dr. Moellering also described work on agents designed to inhibit multidrug resistance (MDR)-like efflux pumps in bacteria such as Staphylococcus aureus or Pseudomonas aeruginosa.
Advances in basic science and molecular biology may also provide new antimicrobial targets, Dr. Moellering pointed out. A number of new approaches, for example, are based on inhibition of bacterial cell functions, such as cell wall synthesis, DNA replication, or transcription. Other strategies involve inhibition of factors relating to bacterial virulence, such as adhesion.
Antisense Antinucleotides
Perhaps the most "difficult" approach, he said, is the use of antisense antinucle-otides to block the growth of microorganisms at the genetic level.
Dr. Moellering also predicted that development of rapid diagnostic and susceptibility tests could help slow the spread of microbial resistance by allowing a narrower therapeutic focus and a reduction in the use of broad-spectrum empiric drug regimens.
