Understanding Bacterial Resistance

BY WILLIAM TOWNSEND, O.D.
JAN. 1997

My daughter Erin questioned me about bacterial resistance, an issue she had been studying in her ninth-grade biology class. She was concerned that in her lifetime, there would be no antibiotics that could be used to treat common diseases. Many doctors share her concern as more and more resistant strains of bacteria appear. The problem is not limited to family practice physicians or infectious disease specialists. It affects anyone who treats patients for bacterial disease.

Inherent differences between animal cells and bacterial cells allow antibiotics to prevent bacterial growth (bacteriostatic) or kill bacteria (bactericidal). Some bacterial species are less susceptible to certain antibiotics. Most antibiotics work in one of four ways: 1) they adversely affect cell wall synthesis; 2) they inhibit protein synthesis; 3) they interfere with nucleic acid synthesis; or 4) they alter bacterial cell membrane function.

RESISTANCE FROM MUTATION

Bacteria can often acquire resistance through mutations, which occur spontaneously and are far more common in bacteria than in more complex organisms. This is primarily because bacteria reproduce so frequently. If a spontaneous mutation allows a bacterium to survive a type of antibiotic, its offspring will share the trait. When a pool of resistant and nonresistant bacteria is exposed to that antibiotic, the nonresistant bacteria will die, creating a void that is soon filled by resistant bacteria. Free from competition, they proliferate and spread to other areas in the patient or to another individual.

TRANSFERRED RESISTANCE

Bacteria can transfer genetic information by conjugation, whereby they join via a 'bridge' between their cytoplasm and exchange DNA. They integrate the new genetic material into their own DNA, acquiring traits which they pass on to their descendants. Bacteria may even acquire DNA fragments that have escaped from the cytoplasm of damaged or lysed bacteria.

The transfer of larger units of DNA (plasmids) is one important means by which antibiotic resistance is passed from one organism to another. Plasmids are relatively large units of extrachromosomal DNA that can be transferred between bacteria. They are known to have contributed to the development of bacterial resistance to tetracyclines, chloramphenicol, streptomycin and the sulfonamides.

HOW RESISTANCE WORKS

Resistant bacteria possess unique attributes that bypass the mechanisms through which antibiotics work. For instance, the beta-lactams (penicillin, cephalosporins) work by binding to 'penicillin binding proteins,' enzymes critical to cell wall synthesis. This inhibits cell wall synthesis, causing cell lysis and death.

Bacterial resistance to these drugs occurs by: 1) production of altered enzymes that have a low affinity for beta-lactams, resulting in normal cell wall synthesis; 2) alteration of the cell membrane for reduced permeability to antibiotics; and 3) production of beta-lactamases, enzymes that inactivate the beta-lactams. All of these alterations in metabolism originated through mutations that were passed from generation to generation, and to other bacteria via plasmids.

WHAT CAN BE DONE

The crisis in bacterial resistance did not happen overnight. Overuse of antibiotics exposed billions of bacteria to antibiotics and the lucky mutants survived. Now we must contend with their offspring.

The real messages here are to avoid the extraneous use of antibiotics and to reserve our best, newest antibiotics for severe infections. Obviously, if a patient suffers a corneal abrasion, it is prudent to prophylactically treat the eye with an antibiotic for a short time. But, if a patient has a viral infection, don't prescribe a topical antibiotic to prevent a secondary infection. Vancomycin is one of the only antibiotics that is effective against resistant Streptococcus B infection. Reserve this drug for severe corneal ulcers that are resistant to all other antibiotics.

Finally, support the companies that spend millions of dollars developing new drugs. There have been great successes such as clavulanic acid. This compound is not an effective antibiotic, but by negating the effects of beta-lactamases, it allows penicillin and other beta-lactams to fight infection. Do not be guilty of handing out samples instead of prescriptions. The money spent to fill prescriptions will help fund research and development of new drugs. CLS

Dr. Townsend is in private practice in Canyon, Texas, and is a consultant at the Amarillo VA Medical Center.