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Antibiotic Resistance, Mutation Rates And MRSA

As worrisome as MRSA is, it is just the tip of the iceberg, so to speak. In fact, there are a number of far more threatening drug-resistant bacteria in existence, such as Pseudomonas aeruginosa. P. Aeruginosa poses a greater threat because it has certain biological features that make it more readily resistant to antibiotics than MRSA. For example, P. Aeruginosa has a highly impermeable outer membrane, whereas MRSA does not. This outer membrane makes it more difficult for antibiotic chemical compounds to actually get inside the bacterial cell so that they can inflict damage. Moreover, once the antibiotic compounds are inside it, P. Aeruginosa has what are known as efflux pumps, which can very quickly pump foreign compounds like antibiotics back out of the cell before they have a chance to do damage. MRSA does not have efflux pumps. Because of these biological features, P. Aeruginosa infections either quickly evolve multidrug resistance or are drug-resistant from the start. Unlike with MRSA, however, the likelihood of picking up a P. Aeruginosa infection from a doorknob in a school building is practically nil. P. Aeruginosa infections occur mostly among hospital patients—at least for now.

In both the hospital and the community, antibiotic resistance has emerged as a major public health problem. In fact, some scientists consider it the most important public health problem of the twenty-first century. The problem exists not just because bacterial mutation rates lead to a rapid accumulation of mutations (including drug-resistant mutations), but also because of the selective pressures that antibiotics impose. If a drug-resistant phenotype were to evolve and there were no antibiotic present, then that phenotype would fare no better than any other bacterial phenotype. In other words, it wouldn't flourish, and it might even die out. It is only when antibiotics are used that drug-resistant phenotypes have a selective advantage and survive.

Of course, not all mutations confer resistance, and most probably have nothing at all to do with resistance. That said, bacterial populations with especially high mutation rates (so-called "hypermutable" strains) often have higher antibiotic resistance rates. For example, in a study of cystic fibrosis (CF) patients infected with P. Aeruginosa (which is a major cause of sickness and death among CF patients), where more than a third of all CF patients had hypermutable P. Aeruginosa infections, the hypermutable populations had higher resistance rates than isolates with "normal" mutation rates (Oliver et al., 2000). Plus, there are other ways that bacteria evolve resistance, in addition to spontaneous nucleotide base mutations. For instance, bacteria can acquire resistance genes through conjugation (i.E., from plasmid DNA) and from recombination with other bacterial DNA following transformation.

The emergence and spread of antibiotic resistance has become such an important public health problem that many federal and state public health agencies now distribute educational posters to encourage "good hygiene" practices—practices that prevent the spread of antibiotic-resistant bacteria from one person to another and help keep those mutant S. Aureus bacteria off doorknobs. Maybe you have seen one of these posters in a school hallway, in a locker room, or in a public bathroom, imploring you to wash your hands with soap and water to help prevent disease.

To make MRSA matters even worse, in 2002, health care workers reported the first cases of vancomycin-resistant MRSA. In other words, even "last-resort" vancomycin doesn't always work. Therein lies the crisis: People are dying from "simple" bacterial infections, all because of a very low mutation rate.

CDC Director Dr. Tom Frieden On MRSA

Hi, I'm Dr. Hansa Bhargava from WebMD and I'm joined today by Dr. Tom Frieden, director of the CDC. Thank you for being here, Dr. Frieden. Let's talk about MRSA infections. They are hard to treat. And more and more parents are worried about the prevention of these. Especially those who have kids in sports where there is close contact. What would you tell these parents?

Tom Frieden, MD

MRSA, methicillin-resistant Staph aureus, is an organism that became resistant in health care facilities and spread to the community. That's exactly what we need to stop from happening with other organisms, by improving detection and control of resistant organisms in our hospitals. In terms of MRSA in the community, there are commonsense, simple, low-cost things that people can do to avoid it. Wash your hands regularly. Shower after having vigorous physical activity. Don't share towels and combs and other things that kids may share and may carry germs on them. These simple things can really reduce the risk. You know sometimes we're looking for the latest, greatest thing and something as simple as hand washing will make the most difference.

Hansa Bhargava, MD

So just back to basics. Simple hand washing. And for parents who do think that their child might have a MRSA skin infection, how can they distinguish the difference between a regular skin infection vs. MRSA?

Tom Frieden, MD

Well, if it doesn't heal, that's a big hint. You want to make sure that if they're cuts or scrapes, they're washed promptly with soap and water. Cover them during the day time at least, so that they don't get more dirt and dirty things in them. Then if you have a fever or nausea or vomiting, you should be assessed and assessed carefully.

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Hansa Bhargava, MD

Hi, I'm Dr. Hansa Bhargava from WebMD and I'm joined today by Dr. Tom Frieden, director of the CDC. Thank you for being here, Dr. Frieden. Let's talk about MRSA infections. They are hard to treat. And more and more parents are worried about the prevention of these. Especially those who have kids in sports where there is close contact. What would you tell these parents?

Tom Frieden, MD

MRSA, methicillin-resistant Staph aureus, is an organism that became resistant in health care facilities and spread to the community. That's exactly what we need to stop from happening with other organisms, by improving detection and control of resistant organisms in our hospitals. In terms of MRSA in the community, there are commonsense, simple, low-cost things that people can do to avoid it. Wash your hands regularly. Shower after having vigorous physical activity. Don't share towels and combs and other things that kids may share and may carry germs on them. These simple things can really reduce the risk. You know sometimes we're looking for the latest, greatest thing and something as simple as hand washing will make the most difference.

Hansa Bhargava, MD

So just back to basics. Simple hand washing. And for parents who do think that their child might have a MRSA skin infection, how can they distinguish the difference between a regular skin infection vs. MRSA?

Tom Frieden, MD

Well, if it doesn't heal, that's a big hint. You want to make sure that if they're cuts or scrapes, they're washed promptly with soap and water. Cover them during the day time at least, so that they don't get more dirt and dirty things in them. Then if you have a fever or nausea or vomiting, you should be assessed and assessed carefully.

Community-associated MRSA: Most Common Cause Of Skin Infection

In a study published in the August issue of The New England Journal of Medicine, UCLA researchers have reported methicillin-resistant Staphylococcus aureus (MRSA) to be the most common cause of skin and soft tissue infection in communities across the nation. Many patients presenting to the emergency room with skin and soft tissue infections were found to be having MRSA infection that was resistant to traditional antibiotics, such as cephalexin and dicloxacillin, used to treat skin infections.

'The study points to the rising prevalence of this type of MRSA and the need for clinicians to culture infections and make sure the proper antibiotic is administered to treat MRSA,' said Dr. Gregory J. Moran, the study's principal investigator and a clinical professor of medicine in the department of emergency medicine and the Division of Infectious Diseases at Olive View–UCLA Medical Center.

Since the 1960s, MRSA has been found in health care settings, generally among patients who have been hospitalized or are in nursing homes. In the last few years, however, a new type of MRSA has emerged, affecting people with no connection to health care settings. Outbreaks of these new strains of MRSA have been reported among athletes, correctional facility inmates and military recruits. Still, the UCLA study demonstrates that the infections appear to be common in people who are not connected to any particular risk group.

'We noticed more patients showing up in our emergency room with infections that turned out to be community-associated MRSA and wanted to see if this was the case nationwide,' said Dr. David Talan, an author of the study and a professor of medicine in the Division of Infectious Diseases and chief of the department of emergency medicine at Olive View–UCLA Medical Center.

Community-associated MRSA most often manifests itself on the skin as a boil or pimple that can be swollen, red and painful, and have discharge.

Researchers cultured the acute skin or soft-tissue infections of 422 patients seen at 11 metropolitan emergency rooms in the United States during August 2004.

Out of those patients, 249, or 59 percent, were found to have MRSA. The proportion of infections caused by MRSA in various cities ranged from 15 to 74 percent.

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Further characterization of the MRSA samples, performed at the Centers for Disease Control and Prevention, revealed that one genetic type accounted for 97 percent of the samples.

'This one genetic type of MRSA is appearing in metropolitan areas across the country,' Moran said. 'More research will determine how prevalent it is in other parts of the nation.'

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Researchers tested the antibiotic resistance of the isolated MRSA samples and found that in 57 percent of cases, doctors had prescribed an antibiotic to which the bacteria were resistant.

'Doctors need to change what they've done for decades, since traditional antibiotics don't work against MRSA,' Talan said. 'We encourage physicians to reconsider antibiotic choices for skin and soft-tissue infections in areas where MRSA is prevalent in the community.'

Talan notes that most MRSA cases are mild, and having the infection drained and keeping it clean resolves the problem. But when antibiotics are needed, it's important to prescribe an effective medication. Sometimes these infections may require hospitalization and, in rare cases, may even be life-threatening.

'It's important for us to identify and properly treat MRSA in order to halt further progression of serious infections and to prevent recurrence,' Moran said.

Researchers tested the effectiveness of different types of antibiotics on the MRSA samples and found that 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline.

The next step, according to Moran, is to compare these different antibiotics in real patients in order to identify an optimal treatment.

The study revealed several potential risk factors for community-associated MRSA. Patients with MRSA were more likely to report a spider bite as the reason for the skin lesion, perhaps thinking it was a bite in absence of other skin problems. Those with MRSA also were more likely to have close contact with a person with a similar infection.

'However, none of these risk factors were consistent enough to help doctors identify cases of MRSA -- it appears now that everyone is at risk,' Moran said. 'So if you think you have a spider bite or other type of skin lesion that is not healing, you want to see your doctor to make sure it's not an infection like MRSA.'

Dr. Rachel J. Gorwitz, an author of the study and a medical epidemiologist at the Centers for Disease Control and Prevention, noted the importance of educating patients in order to avoid transmission. She offered the following guidance:

1. Wash hands often with soap and water to keep them clean, or use an alcohol-based hand sanitizer (if hands are not visibly soiled).2. Don't share towels, razors or other personal items.3. Avoid contact with other people's wounds or bandages.4. Keep breaks in your skin clean and covered and watch for signs of infection, such as redness, warmth and swelling.5. See your doctor if you notice signs of infection; don't try to drain a boil yourself at home.6. If you have a skin infection, keep the infected area covered with a clean, dry bandage until it is healed; wash your hands thoroughly after changing the bandage and put used bandages in the trash.

Source: Eurekalert

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