Microbial Resistance Is a Worldwide Threat

MONTREAL-The emergence of resistant microorganisms is a worldwidethreat, Robert C. Moellering, Jr, MD, said at a plenary sessionof the 19th International Congress of Chemotherapy. While thebalance is still on the side of the clinician, he warned that"we are coming perilously close to running out of targetsfor new antibacterial strategies."

Dr. Moellering, of Deaconess Hospital and Harvard Medical School,and others are sounding the alarm because, "things don'tlook as bright as they did even a few years ago." No newantibacterials were released last year, he reported, partiallybecause "most of the easy targets that allow selective toxicityhave already been discovered" and partially because the processof bringing new drugs to market is extremely expensive.

'Two Curves on a Collision Course'

Dr. Moellering described the decreasing number of effective newantibiotic agents and the rising incidence of resistant organismsas "two curves on a collision course."

He said that resistance has been reported even with some of thenewest classes of antibacterial agents, such as the fluoroquinolonesand carbapenems, as well as with important drugs, such as vancomycin(Vancocin). Moreover, he noted that resistant strains of gram-positiveorganisms such as enterococci, staphylococci, Streptococcuspneumoniae, and others represent a rapidly growing clinicalchallenge.

Current research focused in a number of areas may yield new treatmentapproaches and/or new antimicrobial agents, Dr. Moellering said.The first approach is a classic one: Screening programs may yetidentify antibiotic activity in natural substances that couldbe the source of new agents.

Molecular chemists are synthesizing future generations of antibioticsby modifying side chains of existing agents, Dr. Moellering said.Vancomycin analogs, for example, are being developed to overcomeresistance.

Another major field of antibiotic research concerns developmentof agents such as the beta-lactamase inhibitors that potentiatethe effects of existing antimicrobials. Within this field of study,Dr. Moellering also described work on agents designed to inhibitmultidrug resistance (MDR)-like efflux pumps in bacteria suchas Staphylococcus aureus or Pseudomonas aeruginosa.

Advances in basic science and molecular biology may also providenew antimicrobial targets, Dr. Moellering pointed out. A numberof new approaches, for example, are based on inhibition of bacterialcell functions, such as cell wall synthesis, DNA replication,or transcription. Other strategies involve inhibition of factorsrelating to bacterial virulence, such as adhesion.

Antisense Antinucleotides

Perhaps the most "difficult" approach, he said, is theuse of antisense antinucle-otides to block the growth of microorganismsat the genetic level.

Dr. Moellering also predicted that development of rapid diagnosticand susceptibility tests could help slow the spread of microbialresistance by allowing a narrower therapeutic focus and a reductionin the use of broad-spectrum empiric drug regimens.