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Last Updated

27 Feb 2003

Source: Los Angeles Times, February 24, 2003


A weapon weakened: antibiotics

As bacteria resist Cipro and other drugs, alternatives are not being developed quickly enough. The curable may become incurable.

By Jane E. Allen, Times Staff Writer

Since hitting the market in 1987, Cipro has been the penicillin of its time, good for knocking out a wide variety of infections. But an increasing percentage of bacteria have grown resistant to this powerful antibiotic, narrowing treatment options and reminding us that microbes find ways to overcome every assault.

Researchers writing in the Feb. 18 issue of the Journal of the American Medical Assn. found that in hospital intensive care units, fewer bacteria responsible for respiratory and urinary tract infections are responding to Cipro. An analysis of bacteria samples from hospitals in 43 states plus the District of Columbia found that the percentage of bacteria like Pseudomonas and E. coli that are susceptible to Cipro fell from 89% in 1990-93 to 76% in 2000.

"The biggest fear is we are losing the battle, that nature can stay ahead of us with mutations," said Dr. Keith Beck, an infectious disease specialist at Harbor-UCLA Medical Center in Torrance.

For now, the arsenal isn't empty. Doctors treating vulnerable hospitalized patients can attack infections with so-called gram-negative bacteria like Pseudomonas using existing antibiotics, such as some penicillins and cephalosporins, and aminoglycosides like gentamicin and amikacin. Often, they'll use a combination of these drugs. Instead of overusing fluoroquinolones like Cipro and Levaquin for pneumonia, physicians can still rely on macrolides like erythromycin and clarithromycin (Biaxin) and cephalosporins, which do not create as much gram-negative resistance problems. Although all bacteria have inner-cell membranes, gram-negative bacteria are tough targets because they have an outer membrane that keeps some antibiotics from entering the cell; gram-positive bacteria have a single membrane.

But there's a misperception among consumers that there will always be a new antibiotic around the corner.

"It's not true anymore," said Dr. Stuart B. Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University in Boston. The antibiotic pipeline has slowed in recent years, even as the time it takes for a new drug to lose its effectiveness grows ever-shorter.

For gram-positive bugs, such as streptococcus and staphylococcus, there are powerful new drugs like Zyvox and Synercid and one still in trials called Daptomycin. But for the gram-negatives, there are fewer options. Some promising approaches are coming from small biotechnology companies. Levy started his own to develop new forms of tetracycline that get around the resistance problem. He's also working on molecules that interfere with a bacterium's ability to cause infection.

Although bacteria become resistant through mutations or by picking up resistant genes from other bugs, some of the problem is preventable.

About 75% of all antibiotics prescribed in the United States are given for upper respiratory illnesses: colds, sore throats, bronchitis, sinus and ear infections. Yet, at least half of those prescriptions aren't needed because the infections are caused by viruses, not bacteria. Every time patients take them unnecessarily or improperly -- for example, by not finishing a full course -- the strongest bugs survive the antibiotic hit and flourish.

Levy, founder of the international Alliance for the Prudent Use of Antibiotics, says consumers have come to think antibiotics kill everything: "They believe they're cure-alls; they believe they deserve to have them." And they have ready access through compliant doctors and online pharmacies. He cited the example of Americans stockpiling Cipro after it was prescribed to those potentially exposed to anthrax.

To curb inappropriate use, some hospitals have had success restricting antibiotic prescriptions.

Levy warns that by overusing antibiotics, "we are sowing the seeds of our own destruction. You can't imagine these fabulous drugs are creating in their wake the biggest problem we've ever faced."