MRSA or Methicillin Resistant Staphylococcus aureus
“Despite many accomplishments in the realm of antibiotics and vaccines… It is now clearer than ever that the human species is in the midst of a war with the microbial world—a resilient foe that will never be completely defeated.”
—Anthony S. Fauci, MD
Director, National Institute of Allergy and Infectious Diseases
National Institutes of Health
“I remember it clearly… I thought, ‘Uh-oh, we have a problem.’”
Director, Molecular Epidemiology Lab
SF General Hospital
[Initial comments from the first person to see the genetic fingerprint of
the MRSA clone that would become known as “USA300“]
Staphylococcus aureus is the most common cause of skin, wound and bloodstream infections in hospitalized patients. According to Dr. Ferric Fang, professor of Laboratory Medicine and Microbiology at the University of Washington, “Staph aureus has already colonized about one-third of the world’s population”. The term “MRSA” or Methicillin Resistant Staphylococcus aureus is used to describe those strains of this organism that are resistant to commonly-used antibiotics. Methicillin was an antibiotic used a number of years ago to treat patients with Staphylococcus aureus infections, but it is now no longer used except as a means of identifying this particular type of antibiotic resistance. Experts have so far uncovered 17 strains of MRSA; two of these (clones 15 and 16) are thought to be more transmissible than others and account for about 96 percent of MRSA bloodstream infections.
Symptoms of MRSA include redness, swelling and tenderness, as well as skin infections, boils, urinary tract infections, bone and bone marrow infections, heart valve infections, brain and brain membrane infections, pneumonia, blood poisoning, and Toxic Shock Syndrome. Without treatment or because of incorrect diagnosis and treatment, the MRSA infection spreads rapidly and can lead to respiratory failure, attacking vital organs like the lungs and heart. Survivors are not always returned to their pre-MRSA condition, with many losing limbs, hearing, and/or full use of organs which have become damaged by the pathogen.
Worldwide, an estimated 2 billion people carry some form of S. aureus; of these, up to 53 million are thought to carry MRSA. In the United States, an estimated 95 million carry S. aureus; of these, 2.5 million carry MRSA.
In most hospitals, the only remaining line of defense against the spread of MDR Staph aureus is an antibiotic by the name of Vancomycin. How long it will hold is anybody’s guess. Vancomycin is not yet exhausted for use when Methicillin and others no longer work, but cases of VRSA (S. aureus resistant to Vancomycin) have turned up and many infectious disease specialists believe that it’s only a matter of time before VRSA becomes widespread.
Recently, in a single year alone, 94,000 Americans fell seriously ill after developing MRSA infections, which most picked up in healthcare facilities (hospitals, clinics, nursing homes, etc.). Previously limited to hospital and nursing home patients, MRSA now has a foothold in the U.S. general population and has begun to spread and kill in urban and suburban neighborhoods and communities across the nation.
The number of children in the U.S. being infected with the MRSA Superbug has increased a great deal over the past few years. “Staph aureus lives all over your body, in your fingers, under fingernails, on your skin, but it also likes wet, moist areas of the body,” said Dr. Ina Stephens, University of Maryland Hospital for Children. Research suggests that many children may be carrying the drug-resistant Superbug MRSA in their nasal passages. After obtaining nasal swabs from 1,300 patients in the St. Louis area, investigators at Washington University (St. Louis, MO) concluded that MRSA “is widespread among children in our community.” Dr. Stephens confirms a rise in MRSA-related ear, nose and throat infections in children. “Their hands are continually in their mouth. They suck their fingers, thumb. We occasionally see a nose picker and the organisms are on the finger and under fingernails, so this puts a child at high risk,” she said.
“USA300” San Francisco General Hospital researchers have been chasing a rogue strain of drug-resistant Staph called USA300 since they first isolated it from a patient specimen in 2001. USA300 is one of more than a dozen distinct varieties of MRSA now circulating here in this country. Although the various MRSA strains have been gaining strength as a public health menace for years, USA300 is shaping up as the worst of the lot. And the aggressive and persistent bug keeps getting worse. Now, a variant of this strain, resistant to six major kinds of antibiotics, has been spreading among homosexual men in San Francisco, Boston, New York and Los Angeles.
USA300 is as dangerous as they come; it can attack organs throughout the body, forcing doctors to amputate fingers, toes and limbs. Toxic proteins carried by USA300 have been implicated in infections which cause the frighteningly fast skin and muscle-tissue destruction known as “necrotizing fasciitis”. Thus, the popular nickname which has been given to this bug: “flesh-eating bacteria”.
When this drug-resistant Staph invades the lungs, it can cause a pneumonia that destroys lung tissue and kills a patient within hours. Historically, pneumonia due to MRSA has been confined to health-care settings, representing 10–20% of pathogens that cause hospital and ventilator-associated pneumonia. Now, however, “Community-Acquired” USA300 pneumonia is beginning to make the rounds outside of the healthcare environment. The CA-USA300 strain of MRSA has emerged as a cause of pneumonia, generally after influenza or influenza-like illness and most often among previously healthy patients [Be sure you see “So, What About the Flu?”, below ─ Ed.].
USA300’s most disturbing trait, however, is just how easily it gets around. “It stormed into town and just took over, displacing everything else,” said Dr. Chip Chambers, infectious disease chief for SF General Hospital. “USA300 has a tremendous ability to spread,” said Francoise Perdreau-Remington, Director of the Molecular Epidemiology Lab at San Francisco General, where the strain was first identified. “Now, more than 80 percent of MRSA infections in this hospital are caused by USA300,” Perdreau-Remington said.
Commenting further, the Director indicated, “It has been described in at least 44 states and is now spreading in European countries.” USA300 is now infecting suburban moms, executives, doctors, athletes and children. It has turned up in tattoo parlors and newborn nurseries. People with HIV infection seem especially prone to it, but it also strikes patients, heterosexual as well as homosexual, who have no previous health problems.
Vancomycin is an antibiotic of “last resort”, reserved for the most serious Staph infections. Some dangerous intestinal bacteria have already developed resistance to Vancomycin (see Vancomycin-Resistant Enterococcus, or VRE, below). Because both VRE and USA300 are circulating in hospital environments, some patients are no doubt battling both bugs at the same time. Given the propensity of Staph to swap genes, these patients have the potential of providing fertile ground for the development of an even more dangerous bug. Which is Perdreau-Remington’s great fear: If USA300 were to acquire Vancomycin resistance from VRE, the result would be a virulent new form of Staph, which would spread readily outside the medical setting and be nearly impossible to treat. “This is the horror scenario,” she said. “We have very little time left.”
Dr. Nafsika Georgopapadakou, Editor-in-Chief of Drug Resistance Updates, believes MRSA is similar to a slow moving hurricane, gathering strength and resistance as it spreads. “Once the ‘Superbug’ hits a community or hospital,” asks Dr. Georgopapadakou, “are populations ready to cope?” The implied and obvious answer to this rhetorical question is a most emphatic and decisive “No!” Not by a long shot.
Enterococcus faecium has already acquired resistance to Vancomycin, as we’ve already mentioned above and has become more difficult to treat than MRSA. Vancomycin is an expensive and potentially toxic antibiotic which has been employed as a weapon of last resort when other antibiotics have failed. In 1992, Vancomycin-resistant Enterococcus (VRE) had become the third most frequent causative agent of hospital-acquired wound and urinary tract infections, as well as infections of the blood, brain and heart. In addition, VRE has presented a particular problem with transplant patients who have compromised immunity. As of this writing, some strains of Enterococcus are not killed by any available antibiotic agents. Dr. Tomasz somberly admits, “If you get the infection, you are in the Almighty’s hands.”
Pseudomonas aeruginosa is an opportunistic pathogen. The bacterium takes advantage of an individual’s weakened immune system to create an infection and this organism also produces tissue-damaging toxins. P. aeruginosa causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gastrointestinal infections and a variety of systemic infections. Pseudomonas aeruginosa is also of grave concern to cancer and burn patients as well as those people who are immuno-compromised. The case fatality rate for individuals infected with P. aeruginosa approaches 50 percent.
Hospital acquired (“nosocomial”) infections of multi drug-resistant P. aeruginosaare increasingly recognized worldwide. Since 1998, P. aeruginosa isolatesresistant to all commercially available antimicrobial agentshave been detected. Multi drug-resistant Pseudomonas aeruginosa bacteria are responsible for a significant proportionof episodes of nosocomial pneumonia.
Within the hospital, P. aeruginosa finds numerous reservoirs: disinfectants, respiratory equipment, food, sinks, taps, and mops. This organism is often reintroduced into the hospital environment on fruits, plants and vegetables, as well by visitors and patients transferred from other facilities. Spread occurs from patient to patient on the hands of hospital personnel, by direct patient contact with contaminated reservoirs, and by the ingestion of contaminated foods and water.
Clostridium difficile is a bacterium normally found in the intestines of healthy and ill people alike, most commonly in the elderly and babies. It can cause uncontrolled bouts of diarrhea (up to 50 per day), fever, nausea and abdominal pain. Clostridium difficile–associated disease (“CDAD”) represents a considerable public health hazard. In the United States, it is responsible for more deaths than all other intestinal infections combined. One publication put it this way: “If you catch it, you’ll have the worst diarrhea of your life. Your guts will churn with pain, your temperature will soar, and if you’re elderly or infirm, you may die…and even if you live, it can come back again and again.”
Incidence, hospitalizations, and deaths related to CDAD have been on the rise and the emergence of hyper-virulent strains, which are resistant to multiple antibiotic drugs, has been reported. 253,000 hospitalized patients were affected by C. difficile-associated disease in 2005—more than double the number in 2000, according to the CDC. Also, some C. diff cases are emerging that do not seem to be originating in hospital settings, further confounding experts. A recent article in the World Journal of Gastroenterology stated, “Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers [i.e., those who show no symptoms ─ Ed.] admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors.”
Although you have probably heard little or nothing about it, CDAD has now reached epidemic proportions in a number of states and there are no signs that it is abating. According to researchers Marya D. Zilberberg MD, et al. of the EviMedResearch Group, “In view of the aging U.S. population, this rapid pace of growth is alarming. If this rate of rise, along with the increase in virulence and diminished susceptibility to antimicrobial drug treatments persists, CDAD will result not only in a considerable strain on the U.S. healthcare system but also in rising numbers of deaths related to this disease.”
Now, a new, more virulent strain called NAP1, has emerged that produces about 20 times the toxins of ordinary strains and can cause severe, repeated diarrhea that resists all but the most powerful drugs and can destroy the colon and lead to blood poisoning and death.
Clostridium difficile bacteria produce highly-resistant, infectious spores when they sense that they are under attack from antibiotics or when they encounter conditions unfavorable to their growth and development. Transmission of infection is through the ingestion of these spores which can survive on hard surfaces and floors for years. Standard cleansers do not eliminate C. diff and traditional antibiotic treatments no longer seem to be working, especially in repeat cases.
“Up until the early 2000s, Fluoroquinolone was an effective treatment for C. difficile infection,” quoting Professor Brendan Wren, author from the London School of Hygiene and Tropical Medicine. “We’ve seen that since these strains acquired resistance to this frontline antibiotic, not only is it now virtually useless against this organism, but resistance seems to have been a major factor in the continued evolution and persistence of these strains in hospitals and clinical settings.”
The dark irony here is that, because C. diff is typically kept in check by the healthy bacteria that live in the digestive tract, people often get C. diff infections after treatment with antibiotics, which kill both harmful and healthy bacteria. As it continues to develop resistance to various antibiotics, C. difficile promises to be a horrible scourge to the healthcare setting.
Escherichia Coli Generally, E. coli is a relatively common bacterium found in the human digestive tract and is normally harmless. Some strains, including those linked to food poisoning, can produce symptoms which typically include severe abdominal cramping, sudden onset of watery diarrhea (frequently bloody), vomiting and a low-grade fever. Most often the illness is mild and self-limited, generally lasting 1-3 days. However, some strains of E. coli can cause serious complications of fatal blood poisoning, bladder and urinary tract infection, cystitis, kidney failure, hemorrhagic colitis, Hemolytic Uremic Syndrome, or postdiarrheal thrombotic thrombocytopenic purpura. The elderly are most at risk, particularly those living in nursing homes. In the United States, E. coli is the leading cause of food-borne illness. About 73,000 people are infected by E. coli each year.
Although grapes, lettuce, and tomatoes may look safe and appetizing on your grocer’s shelves, a hidden E. coli toxin (“Shiga toxin”) could be in them and you’d never know until it was too late. Kansas State University food expert T.G. Nagaraja has spent the past decade researching E. coli bacteria and reports that, in addition to the notorious 0157 version which can cause fatal food poisoning in children and the elderly, a new strain of E. coli (known as 026) could now threaten the nation’s food supply. Nagaraja said it “…comes through beef, water or vegetables.” In 2007 alone, over 22 million pounds of beef and vegetables were recalled due to E. coli outbreaks.
Several countries now report cases of antibiotic-resistant E. coli and health officials are particularly concerned about the drug-resistant strains reported in Spain, Israel, Italy, Greece, the UK, and Canada. In these cases, the infection was resistant to four key antibiotics. In Britain, BBC News reported blood poisoning cases caused by E. coli more than doubled in the ten-year period from 1995 to 2005. Canadian scientists are concerned that infections from an antibiotic resistant E.coli bacteria are spreading beyond hospitals into the greater population and have strongly urged global health officials to begin monitoring their spread.
Salmonella Up to 4,000,000 Americans per year suffer from Salmonella poisoning. Caused by eating contaminated food (meat as well as produce), it is characterized by sharp stomach pains, fever and diarrhea and usually lasts from two to five days. The risk of being infected by drug-resistant Salmonella bacteria is increasing dramatically.
One strain of the Salmonella bacteria, known as DT104, is quickly becoming resistant to a wide range of antibiotics. Laboratories across the United States are finding a greatly increased incidence of resistant bacteria when testing Salmonella samples for resistance to five common antibiotics. The drug-resistant Salmonella bacteria were found in just 0.6 percent of samples in 1979. By 1996 the prevalence had risen to 34 percent, researchers from the U.S. Centers for Disease Control and Prevention (CDC) reported.
Using data from three sources, Kathleen Glynn and colleagues discovered that “in the past five years in the United States there has been widespread emergence of a strain” resistant to five major antibiotics. They estimated the resistant bacteria were infecting between 68,000 and 340,000 people each year. According to Stuart B. Levy of Tufts University School of Medicine, “The DT104 strain, whose frequency is rising in the United States, has been plaguing animals and people in Europe for the past decade. There, the organism has acquired resistance to seven drugs that are used to combat it.”
Acinetobacter baumannii Another threat is being posed by multi drug-resistant Acinetobacter baumannii. Acinbetobacter is a type of bacterium present in the environment and can be found in drinking water, soil, sewage and food. Acinetobacter baumannii can cause bloodstream, wound and urinary tract infections, endocarditis, meningitis and respiratory tract infections and are dubbed “MRABs” when they become resistant to antibiotics. In the past few years, several cases have occurred among the U.S. military serving in Iraq. The Acinetobacter baumanii strain was discovered in the soil there and infections attacked their victims through dirty battlefield wounds.
Amid the recent attention focused on the growing impact of methicillin-resistant Staphylococcus aureus and multi drug-resistant Pseudomonas aeruginosa infections, the pathogen Acinetobacter baumannii has been stealthily gaining ground as an agent of serious nosocomial (i.e., “hospital acquired”) as well as community-acquired infection. A. baumannii is a remarkably hardy organism and it has been shown to be able to survive on dry surfaces for five months, posing a challenge to hospital infection control measures. It has been isolated from hospital equipment, bedding, furniture and hospital staff. Furthermore, contamination of hospital devices with MDR A. baumannii isolates has been documented for ventilator tubing, suction catheters, humidifiers, multidose vials of medication, potable water, bedding and improperly sterilized arterial pressure transducers. The ability of A. baumannii to remain viable on hospital surfaces for extended time periods indicates that the hospital is the probable reservoir for MDR A. baumannii infections.
The last two decades have seen an increase in both the incidence and seriousness of A. baumannii infections. Although this organism appears to have a predilection for the most vulnerable patients, community-acquired A. baumannii infection is an increasing cause for concern. The increase in A. baumannii infections has paralleled the alarming development of antibiotic resistance it has demonstrated. The persistence of this organism in healthcare facilities, its inherent hardiness and its resistance to antibiotics results in it being a formidable emerging pathogen. This organism is now considered to be a “major pathogen” and has become no small threat to both hospital and community settings.
Stenotrophomonas maltophilia Scientists in Britain say hospitals could be facing an increasing threat from yet another deadly bacterial infection with the potential to rapidly develop a resistance to drugs. Researchers at the Wellcome Trust Sanger Institute have found the bacteria Stenotrophomonas maltophilia (“Steno”) currently seen in under 1,000 cases, may ultimately prove to be more difficult to treat than Superbugs such as Methicillin-resistant Staphylococcus aureus (MRSA). The study warns the degree of resistance Steno has shown is alarming.
Steno poses a threat to people who are already ill and cases soared by 40% between 2001 and 2006. The elderly, intensive care patients and cancer patients whose immune systems have been weakened through chemotherapy are among those most at risk.
Steno infections spread through wet areas such as taps and shower heads, and can cling to equipment such as ventilator tubes and catheters, growing into a “biofilm” coating which is difficult to remove.
Mycobacterium tuberculosis An estimated one third of the world’s population is infected with Mycobacterium tuberculosis and nearly 9 million people develop disease caused by this bug each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. Because TB is spread by the airborne route, anyone who breathes air containing viable tubercle bacilli is at risk for acquiring M. tuberculosis infection.
During 1985-1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was marked by a substantial number of patients with TB who did not respond to treatment and who eventually died. Physicians and epidemiologists quickly determined that these persons had multi drug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, Isoniazid and Rifampin. Although persons with MDR TB usually can be treated effectively by relying on second-line drugs, these have more side effects and are more expensive and less effective than first-line drugs and require regimens lasting 18-24 months. The cure rate for those who are afflicted with MDR TB is only 50%-60%.
If this wasn’t bad enough, we now find ourselves faced with a far more serious threat than MDR TB. Virtually untreatable strains of M. tuberculosis are emerging globally and have been given the name, “Extensively Drug-Resistant TB” (XDR TB). XDR TB is defined as MDR TB that is not only resistant to first-line, but also resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: Fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (Amikacin, Kanamycin, or Capreomycin). XDR TB has been identified in all regions of the world, including the United States. According to the CDC, “In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era.” In other words, if you should come down with a case of XDR TB, you might as well prepare to meet your Maker.
More than half the TB cases in the United States occur among immigrants who become infected before their arrival in the United States. Lack of continuity of care contributes to treatment default, ongoing transmission, and prolonged illness.
In the early nineties, we published a Special Report for our subscribers, warning them about MDR TB. Back then, MDR TB posed a serious threat. Today, rates of multidrug-resistant tuberculosis remain low here in the U.S., but are starting to inch back up, as hundreds of millions of American citizens and foreigners alike travel here from abroad every year. “We cannot be safe in the U.S.” while drug-resistant TB is an “epidemic in the rest of the world,” said Barbara Seaworth, Medical Director of the Heartland National TB Center in San Antonio. Outbreaks are “absolutely” possible in the U.S., said Dr. Seaworth, who has treated hundreds of patients with drug-resistant strains.
What’s more, due to the recent emergence of XDR TB, the situation has the potential to be far more grim: an outbreak of XDR TB would be a medical nightmare and could easily overwhelm major cities. Outside of the public health community, only limited awareness exists of the potential consequences of XDR TB for the United States and globally. We plan to keep an eye on this and suggest you check our website periodically for updates (biotechnews.com).
Don’t Miss the Big Picture!
Keep in mind, this “Rogues Gallery” is only a partial listing of deadly Superbugs. For example, Klebsiella Pneumoniae, Campylobacter and Streptococcus pneumoniae are also important, pathogenic bacteria which have developed dangerous and often deadly, multi drug-resistant strains which are also on the rise. And, there are others. Plus, we didn’t even mention infections caused by drug-resistant fungi (C. lusitaniae, C. krusei, C. neoformans, Trichosporon spp., A. terreus, S. apiospermum, Fusarium spp., Aspergillus, C. glabrata, C. norvegensis, C. albicans, C. dubliniensis, etc.).
The objective here is not to provide you with a complete encyclopedia of drug-resistant pathogens. Rather, we are trying hard to make sure you see the big picture, which has become global in scale. When you see an article on the subject in the newspaper or a news clip on TV, the content is focused, usually mentioning a single type or strain of Superbug. One week you might read or hear about MRSA. The next week you may see something about CDAD. Then, another week you might hear about E. coli. So far as they go, these isolated snippets of information are fine. At the same time, however, they can be dangerously misleading. You must not get the false impression that hospitals and other healthcare settings are merely having to occasionally deal with only one particular strain of Superbug at a time. No, the battle is far greater than this. We are no longer in a war with a particular strain of either MRSA, or Pseudomonas aeruginosa, or Enterococcus faecium, or Clostridium difficile, or E. coli, or Salmonella, or Acinetobacter baumannii, or Stenotrophomonas maltophilia, or Mycobacterium tuberculosis, etc. Instead, and we can’t possibly emphasize this strongly enough, we are now engaged in a war with all of these multiple microbial adversaries simultaneously and the battlefield is now worldwide. When you enter a hospital or other healthcare setting these days, you should assume that many of these different pathogens may be present, each strain having the potential to cause serious harm.