Community Associated Staphylococcus Aureus

(Sept 9, 2006) In 1877, Louis Pasteur unknowingly described the first antibiotic when he observed that certain bacteria release substances lethal to other bacteria. In 1896, a French medical student, Ernest Duchesne, initially discovered a by-product of soil mold that had the ability to cripple many different types of disease-causing bacteria - an event which would later revolutionize the field of medicine. The substance, now known as Penicillin, was rediscovered by Scottish physician Alexander Fleming in 1928. It became widely available by World War II where its remarkable disease fighting power was used to virtually obliterate the primary cause of death in most wars: bacterial infections resulting from battlefield injuries. Thus Penicillin and its antibiotic successors were hailed as the new miracle drugs of the Twentieth Century.

Since then, antibiotics have enabled millions of people around the world to fight off a host of deadly infections. They have prevented blindness and loss of limb, cured life-threatening diseases like bacterial meningitis, typhoid and rheumatic fever and have eased suffering while saving countless human lives. So dramatic was the impact of antibiotic therapy on staphylococci and other gram-positive infections (streptococci, enterococci) that between the years of 1944 and 1972, science credits the use of antibiotics with extending the normal human life span an average of eight years.

What most people don't know, however, is that just four years after drug companies began mass-producing Penicillin in 1943, microbes began appearing that could resist it.

Survival of the Fittest. Bacteria are everywhere. They live in us, on us and in the environment around us. It is possible for more bacteria to exist in one square inch than there are humans in existence on the earth today. They dwell on the darkest floor of the ocean, populate the peaks of mountains, and flourish in the frozen tundra. Some thrive in the boiling water of natural hot springs. Others have the ability to lie dormant for long periods of time. Still others don't require oxygen. Petrified remains of bacteria have been found on meteorites. The oldest earthly fossils known, nearly 3.5 billion years old, are those of bacteria-like organisms.

Not all of these organisms are necessarily harmful or responsible for human disease. Some bacteria, for example, are necessary to maintain good health; like those that live in the human intestinal tract, helping us digest the food we eat and gain access to nutrients. It's bacteria that put the tang in yogurt, help our bread to rise, aid in the decomposition of waste, and make up the base of the food chain in many ecosystems. Unlike viruses, many bacteria are free living; they can be parasites like viruses, saprophytes (surviving on decaying matter) or autotrophs (self feeders).

Expose them to an antibiotic and a few that have genes to protect them from the drug will always survive. And because bacteria multiply very quickly (sometimes as quickly as once every 20 minutes), a few microbes with these resistant genes can become a colony of millions overnight - all with the ability to resist that antibiotic. Once a strain has become resistant, every person who is infected with it will have the same resistance problem. In fact, scientists who studied bacteria taken from an artic glacier found that the microbes estimated to be over 2,000 years old were already predisposed to withstand certain antibiotics, indicating that resistance is a natural occurrence.

Bacteria develop resistance spontaneously through simple mutation, which are changes that occur in the genetic material, or DNA, of the bacteria as it multiplies which allow it to fight or inactivate the antibiotic. In laboratory studies, scientists have shown these microbes are able to transfer resistant genes from one kind of bacterium to another, almost like bacterial sex. In this way, resistance can spread from one species of bacteria to another species, enabling both bugs to develop multiple resistances to different classes of antibiotics. For example, it's thought the bacterium Haemophilus influenzae, which causes ear infections, gained resistance to the antibiotic Ampicillin during a gene transfer from Escherichia coli in the 1970s.

All of these factors may play a role in the development of a frightening new strain of what was once a rather innocuous bacterium of the genus Staphylococcus, known to most of us as "staph". A few years after Penicillin's widespread use in the 1940's, Penicillin-resistant infections emerged that were caused by the bacterium Staphylococcus aureus (S. aureus). In 1946 the number of Penicillin resistant bacterial infections was fourteen percent. By 1993, the number of Penicillin resistant Staphylococcus aureus infections worldwide was ninety-five percent, with built-in resistance to Penicillin's synthetic variants Ampicillin and Amoxicillin as well. An epidemic of S. aureus-related infections appeared to be developing. In 1960, Beecham and Bristol came out with a semi-synthetic Penicillin known as meticillin (Methicillin) which could not be destroyed by toxic enzymes produced by S. aureus. With the introduction of the new drug, the looming epidemic quickly faded away. The drug made public notice when it saved the life of actress Elizabeth Taylor as she was treated for staphylococcal pneumonia during the filming of the movie Cleopatra, and a new miracle drug was hailed.

By 1961, Methicillin had already begun to meet its match. The first reports of Methicillin-resistant Staphylococcus aureus - now known to medical professionals as MRSA (pronounced Mer-sa) - came from the United Kingdom, followed by reports from other European countries, Japan, and Australia. Seven years later the first case of MRSA was reported in the United States.

For years, most MRSA infections were being reported in hospital or nursing home based settings in older or sicker people whose immune systems were compromised. Risk factors included recent surgery, presence of a percutaneous device or indwelling catheter, or recent dialysis. But the problem began growing. In 1974, the replacement drug Methicillin killed all but two percent of staph germs. By the mid-1990s, it could kill just half of them, and the percentage of staph germs resistant to Methicillin is quickly rising.

According to The World Health Organization (WHO), the numbers now stand that sixty percent of S. aureus worldwide are resistant to Methicillin, and ninety-five percent to Penicillin. In England, where MRSA infections are being tracked with greater accuracy, the number of deaths linked to Methicillin-Resistant Staphylococcus Aureus has risen by 2,236% in just over a decade. Again, these cases most frequently occur among people in hospitals who have weakened immune systems.

But the bug has jumped the bedrail, and several distinct and unprecedented strains of drug resistant MRSA are now spreading around the world, and throughout our community.

Birth of a superbug: Methicillin Resistant Staphylococcus Aureus. Garden variety staph bacteria are the most common cause of skin infections in the United States. Most of these infections are minor and can be treated without antibiotics. Acne, boils, skin abscesses, soft tissue infections (impetigo, cellulitis) and food poisoning are among a host of conditions caused by this germ. The microbes are both pathogenic and invasive, producing leukotoxin and a wide variety of other toxins which kill white blood cells and promote advancement of infection. In more serious cases, staph can spread to the bloodstream, bones, heart, and lungs - with fatal results.

Although there are over 20 strains of Staphylococcus, only Staphylococcus aureus and Staphylococcus epidermidis are significant in their interactions with humans. In 1884, Rosenbach made a study of the gram-positive spherical Staphylococci bacteria which, when viewed under a microscope, resemble tiny clusters of grapes. He described the two pigmented colony types of Staph and proposed the appropriate nomenclature: Staphylococcus aureus (yellow) and Staphylococcus albus (white). S. aureus is also known as Golden Staph because of its color on a microscopic slide. S. albus, (now known as S. epidermidis), is an inhabitant of the skin.

Throughout our lives many potentially infectious bacteria may reside as harmless passengers on our bodies. This is known as colonization - the presence of the bacteria on a person's body without symptoms of an infection, like fever or increased white blood cell count. A person who has been colonized can become a carrier and spread the organisms to others. Colonization of these particular bacteria - S. aureus - usually occurs in the armpit, groin, genital area, throat, or inside the nose, with the nose being the most densely colonized.

You might be surprised to find that according to the US Department of Health and Human Services Centers for Disease Control (CDC), approximately twenty-five to thirty percent of the US population are colonized with everyday strains of Staphylococcus aureus bacteria, without medical event. One to three percent is estimated to be colonized with one of deadly resistant strains (MRSA). Most of these persons are also asymptomatic.

That's because infection and disease can only be caused when these harmful hitch-hiking microbes gain entry in our bodies through a break in the skin, a depressed or immature immune system, or perhaps through external means like the food we eat. Any cut, burn, bite, scratch or other trauma to the skin's surface, for example, provides a foothold for opportunistic organisms to invade and contaminate the body, causing various degrees of infection and disease.

The spider bite that isn't. In the case of Methicillin-resistant Staphylococcus aureus, the microbes produce a tissue-destroying exotoxin which often causes painful redness, swelling and inflammation around wound sites. These infections are notoriously virulent: what might look like a small spider bite may overnight turn into a swollen or pustulant abscess. This spontaneous appearance of a raised red lesion frequently leads both patients and clinicians to confuse MRSA with spider bites.

Despite resistance to most first-line antimicrobials, many infections can be cured with incision and drainage alone. Although mortality rates for patients with community associated MRSA (CA-MRSA) are low, the toxins are capable of causing serious and sometimes deadly infections, including sepsis (blood infection), toxic shock syndrome, and necrotizing fasciitis ("flesh-eating" disease). Most MRSA deaths occur in patients who present with necrotizing pneumonia.

Hospitalization of patients with community associated MRSA is not uncommon, the rates of which can be as high as almost one quarter of those infected. Once identified, MRSA is taken very seriously on a hospital level. Patients typically are put into isolation rooms by health care workers wearing gowns and gloves. Because the bacterium resists almost every type of antibiotic, patients are often placed on an intravenous antibiotic called Vancomycin. Doctors call it "the drug of last resort".

In February of 2005, the New England Journal of Medicine published a study, A Clone of Methicillin-Resistant Staphylococcus aureus among Professional Football Players, which further documented MRSA as an emerging cause of infections outside of health care settings.

During the 2003 football season, eight MRSA infections occurred among 5 of the 58 Rams players (9 percent); all of the infections developed at turf-abrasion sites. MRSA infection was significantly associated with the lineman or linebacker position, perhaps related to greater physical contact, and a higher body-mass index. No MRSA was found in environmental samples; however, Methicillin-susceptible S. aureus was recovered from whirlpools and taping gel, and from 35 of the 84 nasal swabs from players and staff members (42 percent colonization).

That same season MRSA received national attention when two of the Miami Dolphins football players were hospitalized due to an outbreak. That year complications from MRSA caused the death of two young football players, one at Lycoming College in Pennsylvania and another at the University of Tulsa in Arizona.

In 2005, baseball's Baltimore Orioles Sammy Sosa missed 16 games with MRSA in his foot.

MRSA outbreaks are not limited to sports teams. Infectious disease experts have investigated outbreaks of MRSA in locker rooms, and also day care centers, health club communal changing rooms, prison settings, nail salons, military units, dormitory/fraternity housing, among family households and even in hospital nurseries.

MRSA is spread among people in proximate contact with other people who harbor the organism, and community outbreaks usually occur in clusters. Studies link the spread of MRSA to close skin-to-skin contact, pre-existing cuts or skin abrasions, sharing contaminated items (including towels, sports equipment), contact with contaminated surfaces and basins (including whirlpools and footbaths), crowded living conditions, and poor hygiene. Sharing bar soap was known to be a factor in two independent clinical investigations.

Another community-based study demonstrated that close contact with a person colonized or infected with MRSA results in a 7.5-fold greater risk of becoming colonized with MRSA. As one would expect, persons colonized with MRSA have a higher risk of infection, and both MRSA colonization and infections tend to reoccur. In a study of 812 US Army soldiers, three percent were found to be colonized with CA-MRSA. Of those colonized thirty eight percent developed soft tissue infections during the 8 to 10 week study period. The hospitalization rate was twenty percent.

"Just say 'No' to Vanco". Forty years ago when it was discovered certain strains of Staph were becoming resistant to Penicillin, science introduced an antibiotic called Vancomycin. The introduction of Methicillin decreased the use and importance of Vancomycin for a few years; but as the former wonder drug Methicillin became increasingly ineffective against S. aureus strains, Vancomycin has been reinstated as a therapeutic agent. This 1.5 kD glycopeptide is used to kill bacteria when no other drug works; it is the antibiotic to which many physicians must turn when fighting Staphylococcus aureus. But now, four decades after the drug was introduced into circulation, the medical community may be facing an incipient crisis in its use.

Vancomycin is known to the medical community as the "drug of last resort" since it may be the last opportunity a physician may have to eliminate an infection that would otherwise be nearly impossible to kill with any other drug. Due to an increase in MRSA, Vancomycin use has amplified 2.5 fold in the United States from 1987 to 1995. This, by the way, has secondarily led to an increase in another bad bug - Vanocomycin-resistant Enterococci, (see Chart 1). Because of the high likelihood that MRSA will develop resistance to its use, the CDC has adopted the phrase, "Just say no to Vanco", reminding doctors not to prescribe Vancomycin unless absolutely necessary. But it may already be too late.

On July 5, 2005 the world's first fully Vancomycin-resistant staphylococcus germ was discovered in Michigan. A 40 year old diabetic with chronic kidney problems contracted a staph infection in a gangrenous toe. Doctors were able to control the infection by removing infected tissue and keeping symptoms in check with other drugs. This patient apparently did not contract the germ in a hospital, nor did the CDC find it in the center where he received dialysis. Where he was infected has not been pinpointed. But the infection marked an important first: Vancomycin's failure to treat is seen as a warning that there will be future cases of antibiotic-resistant staph.

Novel bugs. No new drugs. A frightening twist to the emerging problem of drug resistant bacteria is that the pharmaceutical pipeline for new antibiotic medicines has virtually dried up. In the past, research and development efforts have provided new drugs in time to treat bacteria that had become resistant to older antibiotics. Unfortunately, that's no longer the case. For economic reasons, major pharmaceutical companies have all but lost interest in the antibiotics market, dramatically scaling back or even eliminating most of their antibacterial research programs.

A confluence of market forces, regulatory costs and sheer complacency has effectively created an antimicrobial drought.

For the past two decades, while worldwide incidence of antibiotic resistance has been on the rise, pharmaceutical companies have cut back their development of new antibiotics in favor of more lucrative markets. These drugs simply are not big moneymakers - especially when compared to those used long term to treat chronic conditions like high blood pressure or high cholesterol.

One sale of a seven to ten day course of erythromycin gleans a tiny fraction of the profits earned by continuous refills of drugs people take for years, like Lipitor, Prevacid or Viagra. Moreover, drug development has become hugely expensive, with direct and indirect costs of bringing a drug to market now averaging between $800 million and a billion dollars. Pharmaceutical companies have stock holders, and stockholders want economic feasibility.

Chart 2 demonstrates the reduction in new products brought to market to help fight bacterial infections in recent decades. Twenty years ago, approximately a half-dozen new antibiotics would appear on the market each year; now it's one or two at most. One year, in 2002, out of 89 new drugs approved by the FDA, not one was an antibiotic.

It is a fact that most antibiotics in use today are chemically related to earlier ones discovered between 1941 and 1968. During the last 37 years, only two antibiotics with truly novel modes of action have been introduced-Zyvox in 2000 and Cubicin in 2003. The world's largest pharmaceutical company, Pfizer, maker of Lipitor and Viagra, is one of the companies still working to come up with new antibiotics. It manufactures Zyvox, which was developed specifically for the treatment of MRSA. But at an average cost of $4,630 per patient, Zyvox is not exactly a godsend.  And, just six years after its release, resistance to the drug has already been developing.

So don't hold your breath for new miracle drug coming around the bend any time soon, even from companies like Pfizer.

An ounce of prevention. We have learned much about the enemy. Germs that once required moisture now survive on paper and dry fabrics. Germs once dependent on a living host can go dormant on inanimate objects for weeks before flashing back to life upon contact with human skin. Some thrive on countertops, handrails, and other surfaces even after cleansing with common household detergents.

Research at sanitation-services company Ecolab Inc. indicates Methicillin-resistant Staphylococcus aureus can survive for days and often weeks on common surfaces like keyboard covers, acrylic fingernails - even bed linen. Scientists inoculated two strains of MRSA onto samples of such surfaces. Over the next eight weeks, the remaining bacteria were counted. It was found that MRSA can survive for five days on bed linen, six weeks on computer keyboard covers, and eight weeks on acrylic fingernails.

In a similar study, researchers from Chicago's Northwestern Memorial Hospital contaminated keyboards with three types of bacteria: Pseudomonas aeruginosa, Vancomycin-resistant Enterococcus faecium, and Methicillin-resistant Staphylococcus aureaus. Results showed that while PSAE survived for one hour, VRE and MRSA both survived up to 24 hours on keyboards. When volunteers touched the contaminated keys, PSAE spread 18% of the time, VRE spread half of the time, and MRSA spread to hands 92% of the time. Further testing carried out in the UK indicate if someone has MRSA on their hands, the bacteria will be left on the following four surfaces touched.

These findings clearly demonstrate the importance of hand washing and disinfection, particularly in shared environments. According to the CDC, the main mode of transmission of MRSA is via hands which may become contaminated by contact with a) colonized or infected persons, b) colonized or infected body sites of the person themselves, or c) devices, items, or environmental surfaces contaminated with body fluids containing MRSA. Hand washing is the single most important behavior in preventing the spread of infectious disease.

Personal hygiene, proper wound care, vigilance towards outbreaks in the community and early treatment appear to be the key. If you do get a skin infection, it's important it's treated like a "normal" skin infection initially through the use of antimicrobials and antiseptics. If the infection does not respond immediately or appears to be systemic, your physician can culture the site. Treatment may include topical application of an antiseptic, antimicrobial skin cleanser combined with oral antibiotics. Hospitalization and IV drugs are an obvious last resort.

Return to the pre-antibiotic era? Bacteria that resist not only single, but multiple antibiotics have become increasingly widespread. It's not just staph. Other diseases related to drug resistance include tuberculosis, streptococcal pneumonia, gonorrhea, typhoid fever, malaria, enterococcal infections (endocarditis, urinary tract infections, etc.). A growing list of bacterial, fungal, viral and parasitic organisms are becoming resistant our front line medications.

The CDC has acknowledged that virtually all significant bacterial infections in the world are becoming resistant to the antibiotic treatment of choice. They caution, "Unless antimicrobial resistance problems are detected as they emerge and actions taken quickly to contain them, the world may soon be faced with previously treatable diseases that have again become untreatable, as in the pre-antibiotic era."

Throughout most of our lifetimes, those of us in civilized countries have enjoyed the protection of medicine's magic bullets. These miraculous lifesavers had seemingly limitless applications and were once considered the universal answer for many infectious diseases. Now, in a global community where half the world can purchase antibiotics over the counter and they are dispensed widely - and not always wisely - for human, animal and agricultural consumption, the picture on the horizon seems quite different.

We can expect future disease processes caused by nature's evolutionary bacteria to become more advanced, more aggressive, and more lethal than ever before. Only time will tell if science can stem the tide.

Dr. Peter Lamelas is an Emergency Medicine Physician and is the owner of MD Now Urgent Care Walk-In Medical Centers in  suburban Lake Worth and Royal Palm Beach, Florida. He was Medical Director of the Emergency Department of Columbia Hospital in West Palm Beach for 17 years. Residency trained in Internal Medicine and Board Certified in Emergency Medicine (ABPS), he is a long standing member of the American College of Emergency Physicians. In 2001, Dr. Lamelas received a gubernatorial appointment to serve on the State of Florida's Board of Medicine. In 1993 he earned his Masters Degree in Business Administration from Nova Southeastern University. 

Company Information 

MD Now Medical Centers 
Lake Worth Location
4570 Lantana Road 
Lake Worth, FL 33463 
Main: 561-963-9881 
Website: www.MyMDNow.com 
Email: info@mymdnow.com

Royal Palm Beach Location
11551 Southern Blvd
Royal Palm Beach, FL 33411
Main: 561-798-9411 

Back to Home Page

In West Palm Beach call 561-963-9881 In Wellington call 561-798-9411. Toll Free 1-888-MDNOW-911