Invasive methicillin-resistant Staphylococcus aureus infections in the United States.

Invasive methicillin-resistant Staphylococcus aureus infections in the United States.

JAMA. 2007 Oct 17

Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators.

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. rmk2@cdc.gov

CONTEXT: As the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed.

OBJECTIVES: To describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005.

DESIGN AND SETTING: Active, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care-associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA).

MAIN OUTCOME MEASURES: Incidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains.

RESULTS: There were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care-associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100,000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100,000; interval estimate, 92.6-156.9), blacks (66.5 per 100,000; interval estimate, 43.5-63.1), and males (37.5 per 100,000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100,000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care-associated infections in all surveillance areas.

CONCLUSIONS: Invasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.

PMID: 17940231 [JAMA]

How staph became drug-resistant threat

How staph became drug-resistant threat

Sunday November 4, 2007

94,000 infections a year, many occurring outside of hospitals

By Jeremy Manier Tribune staff reporter

The evolutionary path of the bacterium called MRSA wound around the globe for decades before a pair of Chicago doctors in 1996 noticed the bug had taken an ominous turn.

Before then, the germ's resistance to antibiotics was of concern mainly in hospitals, where steadily growing numbers of patients were contending with the stubborn staph infection. Reports of healthy people who contracted MRSA outside of a hospital were rare and isolated, the stuff of obscure medical journal articles.

But the bacterium, formally known as methicillin-resistant Staphylococcus aureus, was beginning to depart from the habits it had settled into during years of adaptation to human hosts.

At the University of Chicago Medical Center, pediatric specialists Dr. Robert Daum and Dr. Betsy Herold held an impromptu meeting to discuss a dramatic increase in young patients showing up at the hospital with MRSA infections they'd gotten in the community. Dozens of children were sickened by the resistant bacteria without having contact with hospitals -- an unprecedented outbreak.

"We just looked at each other and said, 'What's going on here?'" said Daum, chief of pediatric infectious diseases at the U. of C.

They were witnessing a pivotal episode in the biography of a bacterial family that is now found widely in hospitals and among the public at large, causing 94,000 severe infections each year with 19,000 deaths, according to a recent federal estimate. From its humble birth at hospitals in Britain, MRSA has transformed itself into a menacing microbe with fewer weaknesses and perhaps more lethal power than its ancestors had.

The germ's years of adaptation did not make it an invulnerable superbug. Some antibiotics still work reliably against MRSA and even severe cases of illness can be treated. But many doctors still do not know how to recognize and properly treat the infection, and experts are concerned potent strains will continue spreading in the community.

The bug's erratic evolutionary story became clear only in the last few years as scientists decoded the full genomes of at least 12 separate staph varieties, making the bacteria among the most intensely studied pathogens in recent memory. Genetic sleuthing has revealed MRSA's family ties and some potential gaps in its armor, as well as the darker corridors of its private life.

Like most successful germs, MRSA has triumphed by constantly changing and adapting to new environments. MRSA does this mostly through an uncanny talent for weird bacterial sex.

It's not sex as humans understand the term, but the effect is the same: a blending of genes from unrelated individuals. MRSA does it with the aid of viruses that siphon DNA from an individual germ and inject it into the next, like microscopic mosquitoes. The bacterium also has the ghoulish ability to suck up genetic material from germs that have died and dissolved.

"This isn't like human biology at all -- after we're born we're stuck with the genes we've got," said MRSA researcher Dr. Henry Chambers, chief of infectious diseases at San Francisco General Hospital. "Staph can take on new genes and share them with friends."

The bacterial ancestors of MRSA have probably stalked humans throughout history. Staph is an ancient, ball-shaped germ that caused skin inflammation and battlefield wound infections long before it encountered the antibiotics that helped spawn MRSA. Scientists identified Staphylococcus aureus as a species in the late 19th Century.

Staph felt the sting of antibiotics before any other bacteria, when British researcher Anthony Fleming discovered penicillin stopped the germ's growth. By the 1950s, however, the bacterium had adapted by making an enzyme that could slice through penicillin. The need for more antibiotics led to a new wave of drugs, including the debut of methicillin in 1959.

Just one year after methicillin hit the market, a young English bacteriologist named Patricia Jevons was testing thousands of bacterial samples and found three strains were resistant to the new drug. Reporting her findings in the British Medical Journal in 1961, Jevons noted calmly, "The fact that the occasional resistant strain does exist should be borne in mind."

No newspaper headlines heralded the birth of MRSA, perhaps because experts already knew it was only a matter of time before staph figured out the new drug. Antibiotics shove bacteria into an evolutionary corner, weeding out the vulnerable varieties and offering an opportunity to strains that have picked up key defensive traits."

We can always expect antibiotic resistance to follow antibiotic use, as surely as night follows day," said Dr. John Jernigan, a medical epidemiologist with the federal Centers for Disease Control and Prevention.

Evolution's answer to methicillin was a gene called mecA that allowed MRSA to evade the antibiotic's molecular weaponry. Scientists searching for its origins have found different versions of the gene in a form of staph that infects rats, as well as in a relatively harmless type of staph that can be found virtually everywhere.

The resistance gene likely hopped repeatedly from one staph species to another, perhaps using the bacterial viruses called phages as its taxi service. The gene "wasn't very common, but it was there in the background, waiting to be amplified," Chambers said.

Landing in the U.S.

MRSA spent its youth in the '60s lurking in the shadows, slowly spreading and gathering force. The bacteria got its U.S. passport in 1968, when the first American cases showed up in Boston. Methicillin fell out of use as a drug because it was toxic to some patients, but MRSA was still resistant to the similar drugs that replaced it.

Then, as today, doctors could still stop the bug with a more powerful antibiotic, vancomycin. But if an infection is not recognized as MRSA, the patient's condition can get dangerously worse while a physician tries to treat it with weaker antibiotics. Doctors typically do not reach first for vancomycin because routine use of the drug could help bacteria build resistance to it as well.

As of 1974 the resistant bug still accounted for only 2 percent of all hospital staph infections. The problem in hospitals grew more quickly in the 1980s before flattening out. MRSA took off first in big-city teaching hospitals, which brought together large numbers of the sickest patients from around the world. Once the bug gained a foothold, it seemed almost impossible to eradicate.

"It's not as though we can point to one organism at one location and say everything emanated from here in logical fashion," said Fred Tenover, acting director of the CDC's office of antimicrobial resistance. "We had progressions, fallbacks; then the bacteria reached a critical mass, got a foothold, and from there you got larger and larger epidemics."

Scattered cases of MRSA cropped up outside of hospitals in Michigan and parts of Australia, but before the 1990s, resistant staph never quite caught on in the community.

Pressures of evolution

The reason may go back to the selective pressures of evolution. Drug resistance doesn't always help bacteria survive. It's vital for germs in a hospital, where the constant use of antibiotics slowly weeds out any bacteria that lack such defenses, but in the community, resistance genes may become a drag.

"Having this extra baggage can take away from the bacteria's fitness, so it's better for the bug not to have it," said Susan Boyle-Vavra, a staph researcher at the University of Chicago.

That's one reason the U. of C. finding of a spike in community-acquired MRSA cases came as such a shock when Daum's team published its results in 1998. Another was that no one had seen this strain of MRSA before. Among other clues, the U. of C. strain could be treated with drugs such as clindamycin, which the common forms of hospital MRSA had learned to resist long before.

Daum began sounding an alarm about the new form of community MRSA, but few people in the media or in the research community took his concern seriously. Community MRSA still seemed rare, and the hospital variety was a bigger problem. Jernigan was one of many experts who argued the new bug had merely escaped from hospitals and posed no unique threat.

"Early on, I wondered if MRSA in the community had its origins in the health-care setting," Jernigan said. "That was wrong. It definitely has its own foothold in the community.

"The unusual properties of MRSA's new form have emerged since 2000 as scientists intensely studied the bug.

Troubling toxin

One of the strain's most potentially troubling features is a gene for a toxin called PVL, which hopped a ride into the staph genome on a bacterial phage. The toxin's role has spurred debate, as some researchers think it's merely a benign passenger. But some studies suggest MRSA with PVL can cause more serious forms of disease, including a severe form of pneumonia.

"If you have bad staph pneumonia, you're likely to have a strain with PVL," Daum said. "It's a convergence of drug resistance and virulence."An even newer strain of community MRSA has swept the country in the last few years and now accounts for nearly all cases. The latest variety appropriated yet another gene from a mostly harmless type of staph that may be helping the new strain spread.

"It can survive inside the cells the body normally uses to kill it," Tenover said. In the latest twist to the story, scientists say the community strain now has begun infecting hospital patients, who may be more vulnerable to it.

Genetic studies of MRSA have brought some good news. Last year researchers from the U. of C. and Rockefeller University in New York reported a successful test in mice of a vaccine that would protect against several forms of MRSA, including one of the community varieties.

It may even be possible to make old antibiotics work against MRSA. Daum's lab has focused on disabling a system of proteins in the bacteria that sense when antibiotics are nearby. Turning off that system makes the bug blind to the drugs that can kill it.

If successful, the approach one day could allow doctors to use standard antibiotics even against germs that possess the resistance gene. For once, MRSA's long evolutionary march could take a welcome step backward.

Avoiding infection

Good hygiene is the best way to avoid infection with MRSA. This staph infection sometimes first appears on the skin as a red, swollen pimple or boil that may be painful or have pus. It can be spread by close, skin-to-skin contact or by touching surfaces contaminated with the germ.

The federal Centers for Disease Control and Prevention advises:

* Keep your hands clean by washing thoroughly with soap and water or using an alcohol-based hand cleaner.

* Keep cuts and scrapes clean and covered with a bandage until healed.

* Avoid contact with other people's wounds or bandages.

* Avoid sharing personal items such as towels or razors.

Tracking MRSA in hospitals and communities

Resistant strains of Staphylococcus aureus have evolved steadily over the years and acquired the ability to spread through the community. Today about 2.3 million Americans carry MRSA in their nose or on their skin.

TIMELINE OF MRSA

Methicillin-resistant Staphylococcus aureus

1959: Methicillin is introduced as an antibiotic.

1961: Bacteriologist Patricia Jevons discovers first methicillinresistant staphylococcus aureus (MRSA) in England hospitals.

1968: First report of MRSA in American hospitals in Boston.

1974: MRSA accounts for 2% of hospital staph infections in U.S.

1981: First reports of MRSA acquired in the community, while MRSA in hospitals rises steadily.

1997: MRSA accounts for 50% of hospital staph infections.

1998: University of Chicago researchers report a 25-fold increase in community-acquired MRSA from 1993 to 1995. During the same period, 35 kids in Chicago are hospitalized with community-acquired MRSA.

1999: CDC reports deaths of four otherwise healthy children from community-acquired MRSA.

2002: U. of C. team finds that new cases of community-acquired MRSA are genetically distinct from hospital strains.

2007: CDC estimates that MRSA causes 94,000 severe infections each year, killing 19,000.

Sources: CDC, University of Chicago, Barry Kreiswirth for The Public Health Research Institute Center

Chicago Tribune

jmanier@tribune.com

MRSA cases higher, but they're still rare

MRSA cases higher, but they're still rare

Posted by the Asbury Park Press on 11/4/07

After days of media hype, the public now knows a lot about Methicillin-resistant Staphylococcus aureus (MRSA), and many of us have come to fear this big bad "superbug."

As an emergency physician, who has successfully treated many types of infections, I feel the need to clarify two common public misconceptions:

There has not been a sudden jump in MRSA cases. Rather, reports of MRSA have been steadily increasing for years.

MRSA is still relatively rare. Only 1 percent of the population carries MRSA, and most of these people do not develop infections — especially if they simply wash their hands. Moreover, most MRSA infections are easily treated, if caught early enough.

What is most alarming about MRSA is its link to the continued inappropriate use of antibiotics. That's why the American College of Emergency Physicians is saying it's important for people to know when — and when not — to seek antibiotics for a range of illnesses. For example, people need to realize they should not be seeking antibiotics for colds or the flu because these illnesses are caused by viruses, which do not respond to antibiotic treatment.

We need to focus less on useless fear-mongering and instead educate the public about why unnecessary use of antibiotics is contributing to a widespread public health problem.

Dr. Laurence DesRochers

TOMS RIVER
PRESIDENT, NEW JERSEY CHAPTER
AMERICAN COLLEGE OF EMERGENCY PHYSICIANS

Ashbury Park Press

Increasing incidence of methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: reconsideration of empiric antimicrobial therapy.

Increasing incidence of methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: reconsideration of empiric antimicrobial therapy.
Am J Surg. 2007 Nov

Awad SS, Elhabash SI, Lee L, Farrow B, Berger DH.
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Hospital, MED VAMC, OCL (112), 2002 Holcombe Blvd, Houston, TX 77030, USA. sawad@bcm.tmc.edu

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) rates are at an all time high. MRSA rates as high as 60% have been reported in patients presenting with skin and soft-tissue infections (SSTIs). Our objectives were to (1) examine the incidence of MRSA over a 7-year period in surgical patients with SSTIs, (2) examine the choice of empiric antibiotic therapy, and (3) evaluate the vancomycin minimum inhibitory concentration (MIC) in MRSA isolates.

METHODS: The medical records of all patients who underwent operative debridement of SSTIs from 2000 to 2006 were retrospectively reviewed. Demographic data such as age, race, and gender as well as co-morbid risk factors were collected. Preoperative American Society of Anesthesiologists (ASA) score, temperature, WBC, creatinine, HgbA1c, albumin, and empiric antimicrobial of choice were also included. Microbiology of all operative cultures was recorded. Available vancomycin MIC data were collected. All data are presented as mean +/- standard error of the mean. A chi-square test was used for statistical analysis.

RESULTS: From 2000 to 2006, 288 patients with operative debridement for SSTIs were identified. The mean age was 54 +/- 11 years. Fifty-two percent of patients had diabetes mellitus, 55% were tobacco users, 34% alcohol users, and 23% had hepatitis C. The mean temperature at presentation was 99.2 degrees +/- 1.5 degrees F. The mean white blood cell count was 13.8 +/- .9. The mean HgbA1c was 8.6 +/- 2.5. The mean body mass index was 30.1 +/- 8. Sixty-seven percent of patients had an ASA > or = 3. There was a significant increase in MRSA SSTIs in 2006 (77%) compared with 2000 (34%, P < .001). Correspondingly, there was a significant increase in empiric administration of vancomycin in 2006 (93%) compared with 2000 (18%, P < .001). The examination of vancomycin MIC shows a shift for MRSA isolates over this time period.

CONCLUSION: Our study shows a significant and ongoing increase in the incidence of MRSA in patients with SSTIs. Empiric coverage with an MRSA antimicrobial should be used as first-line therapy. However, given the observed increase in vancomycin MIC, alternative MRSA antimicrobials should be considered.

Elsevier

Risk factors associated with methicillin-resistant Staphylococcus aureus infection in patients admitted to the ED.

Risk factors associated with methicillin-resistant Staphylococcus aureus infection in patients admitted to the ED.
Am J Emerg Med. 2007 Oct

Viallon A, Marjollet O, Berthelot P, Carricajo A, Guyomarc'h S, Robert F, Zeni F, Bertrand JC.
Emergency and Intensive Care Department, Hôpital de Bellevue, Saint-Etienne, France. alain.viallon@chu-st-etienne.fr

OBJECTIVES: The objective of our study was to define the characteristics of patients admitted to the emergency department (ED) presenting with a methicillin-resistant Staphylococcus aureus (MRSA) infection.

PATIENTS AND METHODS: The study included all patients admitted to the ED between January 2003 and December 2004 in whom a staphylococcal infection was documented. The risk factors associated with carriage of MRSA, the diagnosis made in the ED, and the treatment administered were established from the patients' medical files. The sites from which the bacteria were isolated, the spectrum of resistance of the staphylococci to different antibiotics, and the presence or absence of the gene coding for Panton-Valentin leukocidin for certain S aureus isolates were determined from the reports issued by the bacteriologic department. Two groups of patients were compared: those with an infection caused by MRSA and those with an infection due to methicillin-susceptible S aureus (MSSA).

RESULTS: A total of 238 patients were included, 93 presenting with an infection caused by MRSA and 145 an infection due to MSSA. The patients harboring MRSA had a higher median age than those carrying MSSA (74 vs 61 years, P = .0001), experienced a greater loss of autonomy (according to the Knauss index), and had more comorbidity factors. Nine patients, younger than 40 years, presented with an infection due to MRSA in the absence of any comorbidity factor or any factor associated with carriage of these bacteria. Seven patients in the MRSA group were tested for Panton-Valentine leukocidin genes, and a positive result was obtained in 2 of them. Regardless of whether the infection was caused by MRSA or by MSSA, the bacteria were most frequently isolated from a cutaneous site, in 40% and 65% of the patients, respectively. Irrespective of the group, 28% of the patients presented with bacteremia. The spectrum of resistance of these MRSA strains suggested a hospital rather than community origin. The initial antibiotic therapy was rarely appropriate in the case of an infection due to MRSA.

CONCLUSION: Infections caused by MRSA accounted for a high proportion of the staphylococcal infections diagnosed in the ED, necessitating a rational approach to the prescription of antibiotics for infections of this type.

Elsevier

Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power.

Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power.

Curr Opin Microbiol. 2007 Oct 5

de Lencastre H, Oliveira D, Tomasz A.

Laboratory of Microbiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica (ITQB) da Universidade Nova de Lisboa (UNL), 2780 Oeiras, Portugal.

Nothing documents better the spectacular adaptive capacity of Staphylococcus aureus than the response of this important human and animal pathogen to the introduction of antimicrobial agents into the clinical environment. The effectiveness of penicillin introduced in the early 1940s was virtually annulled within a decade because of the plasmid epidemics that spread the ss-lactamase gene through the entire species of S. aureus.

In 1960 within one to two years of the introduction of penicillinase resistant ss-lactams (methicillin), methicillin resistant S. aureus (MRSA) strains were identified in clinical specimens. By the 1980s, epidemic clones of MRSA acquired multidrug resistant traits and spread worldwide to become one of the most important causative agents of hospital acquired infections. In the early 2000s, MRSA strains carrying the Tn1546 transposon-based enterococcal vancomycin resistant mechanism were identified in clinical specimens, bringing the specter of a totally resistant bacterial pathogen closer to reality.

Then, in the late 1990s, just as effective hygienic and antibiotic use policies managed to bring down the frequency of MRSA in hospitals of several countries, MRSA strains began to show up in the community.

PMID: 17921044 [PubMed - as supplied by publisher]

MRSA cases fall by 10% in UK

MRSA cases fall by 10% in UK

Thursday, 01 Nov 2007 15:41

Cases of the healthcare-associated infection (HCAI) MRSA have fallen by ten per cent in the last year, statistics have revealed today.

The Health Protection Agency (HPA) said there were 6,381 reported cases of MRSA in England between April 2006 and March 2007.

This compares to 7,096 in the same period for the previous year. Cases of MRSA in the last quarter also fell by ten per cent.

There has been a 12 per cent decrease in reported cases of MRSA blood poisoning since mandatory surveillance began in 2001, with falls seen in all types of acute NHS trusts.

Health secretary Alan Johnson has described today's figures as "encouraging".

Although cases of the HCAI Clostridium difficile (C.difficile) in the over-65s rose by seven per cent between 2005 and 2006, the latest quarterly figures show a 13 per cent drop in cases during April to June in 2007 compared to January to March.

The HPA also published its first results of C.difficile cases in people aged between two and 64; 2,890 were reported between April and June 2007. It is estimated that 84 per cent of all infections occur in people aged over 65.

The agency said today's figures should be treated with caution, however, as there have been recent changes to the surveillance system that could have impacted on them, such as the extension of the mandatory surveillance to patients aged two years and over.

Commenting on the figures, Professor Pete Borriello, director of the centre for infections, said some trusts had made a "significant impact" on MRSA infection rates despite heavy workloads.

But he added: "More work needs to be done to see the same level of decrease with C.difficile and we are encouraging trusts to use the figures to raise the profile of local infection control practices and make changes where the results indicate this may be necessary."

Dr Georgia Duckworth, head of the agency's HCAI department, said: "There can be, and have been, significant reductions for some infections."This is particularly notable for MRSA blood poisoning, particularly when these infections are placed in the context of significant increases in hospital activity. This is a major achievement against the seemingly unstoppable rise in MRSA bloodstream infections throughout the 1990s."

Health secretary Alan Johnson said the government is "determined to tackle" HCAIs.

"We are the only country in the world to impose mandatory, universal surveillance of MRSA and C.difficile including for the first time gathering information on C.difficile in those under 65. We have also raised the bar to ensure that the highest possible hygiene standards are set for trusts," he added.

"The measures that we have introduced over the past months - including £50 million funding to reduce infections, increasing the number of matrons to 5,000, 'bare below the elbows' guidance, the establishment of the Care Quality Commission and plans to screen all patients for MRSA - show that ensuring patient safety is our absolute priority."

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