ࡱ> VXU a3bjbj,, XNNa+^^33333$W$3{(@EEEEfEEEVR@5+34  0 EEj^ :   The Problem of Antibiotic Resistance Overview The triumph of antibiotics over disease-causing bacteria is one of modern medicine's greatest success stories. Since these drugs first became widely used in the World War II era, they have saved countless lives and blunted serious complications of many feared diseases and infections. After more than 50 years of widespread use, however, many antibiotics don't pack the same punch they once did. Over time, some bacteria have developed ways to outwit the effects of antibiotics. Widespread use of antibiotics is thought to have spurred evolutionary changes in bacteria that allow them to survive these powerful drugs. While antibiotic resistance benefits the microbes, it presents humans with two big problems: it makes it more difficult to purge infections from the body; and it heightens the risk of acquiring infections in a hospital. Diseases such as tuberculosis, gonorrhea, malaria, and childhood ear infections are now more difficult to treat than they were decades ago. Drug resistance is an especially difficult problem for hospitals because they harbor critically ill patients who are more vulnerable to infections than the general population and therefore require more antibiotics. Heavy use of antibiotics in these patients hastens the mutations in bacteria that bring about drug resistance. Unfortunately, this worsens the problem by producing bacteria with greater ability to survive even our strongest antibiotics. These even stronger drug-resistant bacteria continue to prey on vulnerable hospital patients. To help curb this problem, the Centers for Disease Control and Prevention (CDC) provides hospitals with prevention strategies and educational materials to reduce antimicrobial resistance in health care settings. According to CDC statistics * Nearly two million patients in the United States get an infection in the hospital each year * Of those patients, about 90,000 die each year as a result of their infection-up from 13,300 patient deaths in 1992 * More than 70 percent of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them * Persons infected with drug-resistant organisms are more likely to have longer hospital stays and require treatment with second or third choice drugs that may be less effective, more toxic, and more expensive In short, antimicrobial resistance is driving up health care costs, increasing the severity of disease, and increasing the death rates from certain infections. Environment Forces Evolutionary Change A key factor in the development of antibiotic resistance is the ability of infectious organisms to adapt quickly to new environmental conditions. Bacteria are single-celled creatures that, compared with higher life forms, have small numbers of genes. Therefore, even a single random gene mutation can greatly affect their ability to cause disease. And because most microbes reproduce by dividing every few hours, bacteria can evolve rapidly. A mutation that helps a microbe survive exposure to an antibiotic drug will quickly become dominant throughout the microbial population. Microbes also often acquire genes, including those that code for resistance, from each other. The advantage microbes gain from their innate adaptability is augmented by the widespread and sometimes inappropriate use of antibiotics. A physician, wishing to placate an insistent patient ill with a cold or other viral condition, sometimes inappropriately prescribes antibiotics. Also when a patient does not finish taking a prescription for antibiotics, drug-resistant microbes not killed in the first days of treatment can proliferate. Hospitals also provide a fertile environment for drug-resistant germs as close contact among sick patients and extensive use of antibiotics force bacteria to develop resistance. Another controversial practice that some believe promotes drug resistance is adding antibiotics to agricultural feed. A Growing Problem For all these reasons, antibiotic resistance has been a problem for nearly as long as we've been using antibiotics. Not long after the introduction of penicillin, a bacterium known as Staphylococcus aureus began developing penicillin-resistant strains. Today, antibiotic-resistant strains of S. aureus bacteria as well as various enterococci-bacteria that colonize the intestines-are common and pose a global health problem in hospitals. More and more hospital-acquired infections are resistant to the most powerful antibiotics available, methicillin and vancomycin. These drugs are reserved to treat only the most intractable infections in order to slow development of resistance to them. There are several signs that the problem is increasing: * In 2003, epidemiologists reported in The New England Journal of Medicine that 5 to 10 percent of patients admitted to hospitals acquire an infection during their stay, and that the risk for a hospital-acquired infection has risen steadily in recent decades. * Strains of S. aureus resistant to methicillin are endemic in hospitals and are increasing in non-hospital settings such as locker rooms. Since September 2000, outbreaks of methicillin-resistant S. aureus infections have been reported among high school football players and wrestlers in California, Indiana, and Pennsylvania, according to the CDC. * The first S. aureus infections resistant to vancomycin emerged in the United States in 2002, presenting physicians and patients with a serious problem. In July 2002, the CDC reported that a Michigan patient with diabetes, vascular disease, and chronic kidney failure had developed the first S. aureus infection completely resistant to vancomycin. A similar case was reported in Pennsylvania in September 2002. * Increasing reliance on vancomycin has led to the emergence of vancomycin-resistant enterococci infections. Prior to 1989, no U.S. hospital had reported any vancomycin resistant enterococci, but over the next decade, such microbes have become common in U.S. hospitals, according to CDC. * A 2003 study in The New England Journal of Medicine found that the incidence of blood and tissue infections known as sepsis almost tripled from 1979 to 2000.  HYPERLINK http://www.niaid.nih.gov/factsheets/antimicro.htm http://www.niaid.nih.gov/factsheets/antimicro.htm April 11, 2005 Stop Taking Antibiotics When You Feel Better? Taking a shorter course of antibiotics may be just as effective, plus do a better job at preventing antibiotic resistance. By HYPERLINK "http://discovermagazine.com/authors/adam-hadhazy" Adam Hadhazy|Thursday, August 28, 2014 Conventional wisdom:Antibiotic regimens should be taken in full, even after the patient feels healthy again. Contrarian view:Shorter courses are often just as effective and do a better job at preventing antibiotic resistance. You know the drill: When youre prescribed a typical seven- to 14-day antibiotic course, do not, repeat,do notforget to take all the drugs. This take-all-your-pills orthodoxy, championed since the discovery of antibiotics some 70 years ago, is based on eliminating all bacterial culprits as quickly as possible. Doing so, in theory, reduces the odds that the bugs will develop random mutations or pick up drug-resistant genes from other bacteria. Plus, the sustained antibiotic onslaught supposedly ensures that any hardier, partially drug-resistant bacteria also succumb, and thus dont pass on stepping-stone genes leading to full-blown resistance. An emerging view, however, suggests that standard long antibiotic courses are wrong on both counts theyre no better than shorter courses and actually promote antibiotic resistance. The science is clear, says infectious disease specialist Brad Spellberg of the Los Angeles Biomedical Research Institute. Every study that has been done comparing longer versus shorter antibiotic therapy has found shorter therapy just as effective. A few days of taking antibiotics, it seems, should usually be enough to knock infections on their heels, allowing the patients immune system to come in and mop up. Taking the full course of antibiotics unnecessarily wastes medicine, and more drugs translates to increased evolutionary pressure on the harmless bacteria in our bodies. These good bugs can develop drug-resistant genes, which can then transfer to bad bugs. Furthermore, wiping out drug-susceptible bacteria in infections too quickly makes it easier for drug-resistant bacteria to compete over a hosts resources. Better access to nutrients lets the mutant bugs multiply far more rapidly, upping the odds that theyll reach a so-called transmissible density. That means the resistant bacteria proliferate so much that they can escape and infect another person. In essence, if you take all those extra antibiotics, you might be doing the worst bugs dirty work for them by removing a check on their growth. Shorter antibiotic regimens, in contrast, intentionally allow some susceptible bacteria to survive in order to help suppress any resistant pathogens. A recent study showed just this: Mice infected with both drug-susceptible and drug-resistant malaria, when treated less aggressively, were 150 times less likely to pass on the resistant pathogens. Multiple studies demonstrate how doctors might gauge when to end antibiotic therapy. (See Less Is More? Selected Studies below.) Thriving bacteria raise blood levels of the hormone precursor procalcitonin, for example; guiding treatment based on procalcitonin concentrations led to half as much antibiotic use across seven studies, with no drop in cure rates. More signs of improved health, such as fever alleviation, could also indicate antibiotics are no longer necessary. Overall, the accumulating data lend support to the heretical notion of patients, in consultation with their doctors, stopping their pill-popping upon feeling better. The issue of continuing therapy until all doses are done is an old wives tale, Spellberg says. Theres no data to support it. You cant make a cured patient better. Less Is More? Selected Studies Mild to moderate pneumonia:Three days is as effective as eight (el Moussaoui et al., 2006,British Medical Journal); four studies suggest three days is as effective as fivein children (Haider et al., 2008,Cochrane Database of Systematic Reviews). Hospital-acquired ventilator-associated pneumonia:Eight days is as effective as 15 (Chastre et al., 2003,Journal of the American Medical Association); eight studies suggest for certain pneumonias, seven- to eight-day courses have better outcomes than 10 to 15 (Pugh et al., 2011,Cochrane Database of Systematic Reviews). Acute pyelonephritis (kidney infection):Seven days is as effective as 14 (Sandberg et al., 2012,The Lancet). 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