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
(Vancocin). Moreover, he noted that resistant strains of gram-positive
organisms such as enterococci, staphylococci, Streptococcus
pneumoniae, and others represent a rapidly growing clinical
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
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.
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.