Portal de Periódicos da CAPES

The Many Faces of MRSA: Community-Acquired Infection Knows No Bounds

2008; Elsevier BV; Volume: 51; Issue: 3 Linguagem: Inglês

10.1016/j.annemergmed.2008.01.320

1097-6760

Maryn McKenna,

Bacterial Identification and Susceptibility Testing

The patient, a man in his 20s, walked into the emergency department (ED) on an autumn afternoon complaining of pain from a fist-sized lump under the right corner of his jaw. The residents who had rounded on him recited their findings. He was not febrile. He was having no dental pain. The lump was thick-walled and unyielding and its outer temperature matched the nearby skin. Peter Deblieux, MD, director of emergency services at Louisiana State University Interim Hospital, asked for a syringe to aspirate it. “If we get clear fluid, it may be a brachial cleft cyst,” he said. “If we get frank pus, it’s probably a staph infection. But I don’t think it’s a staph infection, unless it’s a nontypical one.” Deblieux masked the syringe with his free hand—the patient had confessed he was terrified of needles—slid the needle in, and smoothly pulled back. The cylinder filled with a creamy, cloudy substance streaked with red. “It’s pus,” Deblieux said disbelievingly. “I was not expecting that.” Ten years since it was first recognized as a significant pathogen, community-associated methicillin-resistant Staphylococcus aureus, CA-MRSA, still retains the element of surprise. As the organism increases in prevalence, as both a leading cause of skin and soft tissue infections and the source of rare and deadly syndromes such as septic arthritis and necrotizing pneumonia, it is becoming an important issue for ED personnel. EDs have been sentinel observation points for the rise of CA-MRSA nationwide. ED personnel handle much of the burden of CA-MRSA disease, often because community physicians have treated the bug inappropriately. As the paradigm of staph treatment changes, ED physicians are effectively modeling best practices for the rest of the medical community. And a few reports suggest that, as CA-MRSA becomes more common, ED staff may play a role in passing the organism to other patients, and may be at greater risk of acquiring the bug themselves. CA-MRSA’s time in the public eye has been short compared to the 60 years since bacteriologist Mary Barber confirmed the first instances of penicillin-resistant S. aureus at London’s Hammersmith Hospital,1Barber M. Staphylococcal infection due to penicillin-resistant strains.BMJ. 1947; : 863-865Crossref PubMed Scopus (53) Google Scholar or the 47 years since Barber’s colleague Patricia Jevons reported the first signs of staph’s resistance to the synthetic penicillin replacement methicillin and related beta-lactam antibiotics.2Jevons M. “Celbenin”-resistant staphylococci.BMJ. 1961; : 124-125Crossref Scopus (1329) Google Scholar Jevons’ finding ushered in several decades in which methicillin-resistant staph became a feared nosocomial pathogen. It sparked ferocious outbreaks in critical care units: In 1980, in just one example, a burn patient transferred to Harborview Medical Center in Seattle transmitted MRSA to 34 other patients in 15 months despite the staff’s best efforts at infection control, and 17 of the patients died.3Locksley R.M. Cohen M.L. Quinn T.C. et al.Multiply antibiotic-resistant Staphylococcus aureus: introduction, transmission, and evolution of nosocomial infection.Ann Intern Med. 1982; 97: 317-324Crossref PubMed Scopus (166) Google Scholar That outbreak also signaled how formidably resistant the hospital strain of staph would become: the original patient’s isolate was resistant to quinolones, clindamycin, erythromycin, trimethoprim, and gentamicin in addition to the beta-lactams. MRSA has become so entrenched in US hospitals that when the quality-focused Institute for Healthcare Improvement expanded its “100,000 Lives” campaign into a new “5 Million Lives” campaign a year ago, it listed “prevent MRSA infections” as one of its most important goals.4“Protecting 5 Million Lives”.http://www.ihi.org/NR/rdonlyres/A96E0639-A979-44F6-A0FF-20329E492F44/4230/5MillionLivespressreleaseupdatedDec26FINALFINAL.pdfDate: 2006Google Scholar A 7-year study published in 2004 found that S. aureus is the second-most common cause of bloodstream infections in US hospitals, and that the proportion of staph infections that were methicillin-resistant rose from 22% to 57%.5Wisplinghoff H. Bischoff T. Tallent S.M. et al.Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.Clin Infect Dis. 2004; 39: 309-317Crossref PubMed Scopus (3320) Google Scholar A separate study found that MRSA incidence in ICUs rose from 36% in 1992 to 64% in 2003.6Klevens R.M. Edwards J.R. Tenover F.C. et al.Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in intensive care units in US hospitals, 1992-2003.Clin Infect Dis. 2006; 42: 389-391Crossref PubMed Scopus (442) Google Scholar Hospital patients infected with MRSA cost more to treat, have longer lengths of stay, and have a higher risk of death than patients with non-resistant staph.7Cosgrove S.E. Qi Y. Kaye K.S. et al.The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges.Infect Control Hosp Epidemiol. 2005; 26: 166-174Crossref PubMed Scopus (738) Google Scholar But across that 40-year span, infectious disease dogma held that MRSA could not survive outside the hospital environment because its load of resistance factors crippled its evolutionary fitness. When resistant staph was found in the community, it was held to be a leak from hospitals that could not sustain transmission in the outside world. That view was fatally challenged in 1998, when Robert S. Daum, MD, and the pediatric infectious diseases team of the University of Chicago Hospitals responded to an anecdotal impression of more MRSA cases on their service by conducting a chart review. Their paper—published in the Journal of the American Medical Association after first being turned down by the journal’s editors—outlined a sharp difference between cases from 1988-1990 and 1993-95, including a 25-fold increase in those with no links to the health care system.8Herold B.C. Immergluck L.C. Maranan M.C. et al.Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk.JAMA. 1998; 279: 593-598Crossref PubMed Scopus (1257) Google Scholar In 2002 the group’s laboratory arm published the microbiology behind the change: a new type of MRSA had emerged with a distinctive molecular fingerprint, a unique suite of toxins, and a shorter chromosomal cassette that retained resistance only to penicillins and cephalosporins.9Daum R.S. Ito T. Hiramatsu K. et al.A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds.J Infect Dis. 2002; 186: 1344-1347Crossref PubMed Scopus (265) Google Scholar Daum’s work, together with a 1999 investigation by the US Centers for Disease Control and Prevention into the deaths of 4 children from necrotizing pneumonia and sepsis,10Centers for Disease Control and PreventionFour Pediatric Deaths from Community-Acquired Methicillin-Resistant Staphylococcus aureus—Minnesota and North Dakota, 1997–1999.MMWR. 1999; 48: 707-710PubMed Google Scholar permanently shattered the paradigm that all resistant staph strains were hospital escapees. They paved the way for the recognition of significant skin and soft tissue infections caused by CA-MRSA in children in day care programs11Shahin R. Johnson I.L. Jamieson F. et al.Methicillin-resistant Staphylococcus aureus carriage in a child care center following a case of disease Toronto Child Care Center Study Group.Arch Pediatr Adolesc Med. 1999; 153: 864-868Crossref PubMed Scopus (147) Google Scholar; high school athletes12Lindenmayer J.M. Schoenfeld S. O’Grady R. et al.Methicillin-resistant Staphylococcus aureus in a high school wrestling team and the surrounding community.Arch Intern Med. 1998; 158: 895-899Crossref PubMed Scopus (253) Google Scholar; native traditional sauna users13Baggett H.C. Hennessy T.W. Rudolph K. et al.Community-onset methicillin-resistant Staphylococcus aureus associated with antibiotic use and the cytotoxin Panton-Valentine leukocidin during a furunculosis outbreak in rural Alaska.J Infect Dis. 2004; 189: 1565-1573Crossref PubMed Scopus (226) Google Scholar; pro football players14Kazakova S.V. Hageman J.C. Matava M. et al.A clone of methicillin-resistant Staphylococcus aureus among professional football players.N Engl J Med. 2005; 352: 468-475Crossref PubMed Scopus (639) Google Scholar; jail inmates15Pan E.S. Diep B.A. Carleton H.A. et al.Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails.Clin Infect Dis. 2003; 37: 1384-1388Crossref PubMed Scopus (166) Google Scholar; and men who frequented sex clubs.16Lee N.E. Taylor M.M. Bancroft E. et al.Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men.Clin Infect Dis. 2005; 40: 1529-1534Crossref PubMed Scopus (141) Google Scholar And they fueled the growing understanding of CA-MRSA as the cause of serious and sometimes fatal invasive infections: sepsis,17Mongkolrattanothai K. Boyle S. Kahana M.D. et al.Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates.Clin Infect Dis. 2003; 37: 1050-1058Crossref PubMed Scopus (204) Google Scholar necrotizing fasciitis,18Miller L.G. Perdreau-Remington F. Rieg G. et al.Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles.N Engl J Med. 2005; 352: 1445-1453Crossref PubMed Scopus (856) Google Scholar osteomyelitis,19Gonzalez B.E. Teruya J. Mahoney Jr., D.H. et al.Venous thrombosis associated with staphylococcal osteomyelitis in children.Pediatrics. 2006; 117: 1673-1679Crossref PubMed Scopus (174) Google Scholar Waterhouse-Friderichsen syndrome,20Adem P.V. Montgomery C.P. Husain A.N. et al.Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children.N Engl J Med. 2005; 353: 1245-1251Crossref PubMed Scopus (234) Google Scholar and necrotizing pneumonia with a 50% mortality rate.21Gillet Y. Vanhems P. Lina G. et al.Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin.Clin Infect Dis. 2007; 45: 315-321Crossref PubMed Scopus (255) Google Scholar Emergency physicians were far ahead of the curve in recognizing CA-MRSA as a new and distinct phenomenon. At Olive View-UCLA Medical Center near Los Angeles—a city that was one of the early epicenters of CA-MRSA, with a huge and still ongoing outbreak in the county jail22Centers for Disease Control and PreventionPublic Health Dispatch: Outbreaks of Community-Associated Methicillin-Resistant Staphylococcus aureus Skin Infections—Los Angeles County, California, 2002-2003.MMWR. 2003; 52: 88Google Scholar—David Talan, MD, and Gregory Moran, MD, were routinely culturing patients with skin infections for enrollment into clinical trials of antimicrobials. “Around 2000-2001, we started seeing all these people who were growing MRSA from their skin infections and who had none of the usual (health care-associated) risk factors,” Moran said. “It was a new and unusual thing, and had implications for us because they had to come out of our studies as well.” An analysis of their culture data, published in Emerging Infectious Diseases in June 2005, revealed a rising proportion of MRSA skin infections, from 29% of isolates in 2001-2002 to 64% in 2003-2004. Susceptibility testing confirmed the infecting organism was not the hospital strain, and molecular fingerprinting revealed patterns indistinguishable from the ongoing CA-MRSA jail outbreak.23Moran G.J. Amii R.N. Abrahamian F.M. et al.Methicillin-resistant Staphylococcus aureus in community-acquired skin infections.Emerg Infect Dis. 2005; 11: 928-930Crossref PubMed Scopus (228) Google Scholar Simultaneously, a group at University of California-San Francisco conducted a prospective convenience sample analysis of skin and soft tissue infections at the Alameda County Medical Center’s ED in Oakland. The research, published in this journal in March 2005, found that 51% of the infection-site cultures grew MRSA, and 99% of the MRSA isolates possessed the SCCmecIV cassette that marks the community strain.24Frazee B.W. Lynn J. Charlebois E.D. et al.High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections.Ann Emerg Med. 2005; 45: 311-320Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar In a commentary published in the same issue, Moran raised a concern that has since proved to be problematic across the country: whether and when to change empiric therapy for skin and soft tissue infections from the go-to drug, the cephalosporin Keflex (cephalexin).25Moran G.J. Talan D.A. Community-associated methicillin-resistant Staphylococcus aureus: is it in your community and should it change practice?.Ann Emerg Med. 2005; 45: 321-322Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar As if an occult hand had clicked “Print,” other papers confirming CA-MRSA’s emergence arrived quickly. An analysis of data from hospitals and public health departments in the CDC’s Active Bacterial Core Surveillance program found that 8 to 20% of all MRSA isolates were the community strain, defined by susceptibility testing.26Fridkin S.K. Hageman J.C. Morrison M. et al.Methicillin-resistant Staphylococcus aureus disease in three communities.N Engl J Med. 2005; 352: 1436-1444Crossref PubMed Scopus (1299) Google Scholar A prospective study of patients admitted to Grady Memorial Hospital, Atlanta’s downtown public hospital (where many patients arrive via the ED), found that 72% of staph infections there were MRSA and 87% of the MRSA isolates were the community strain by molecular fingerprint and susceptibility patterns.27King M.D. Humphrey B.J. Wang Y.F. et al.Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections.Ann Intern Med. 2006; 144: 309-317Crossref PubMed Scopus (656) Google Scholar And finally, Moran and his colleagues in the Emergency ID Net Study Group reported in the New England Journal of Medicine that MRSA was the most common cause of skin and soft tissue infections during one month at 11 university-affiliated EDs across the country, that 97% of the MRSA isolates were CA-MRSA by molecular fingerprinting, and that 74% were a single dominant strain.28Moran G.J. Krishnadasan A. Gorwitz R.J. et al.Methicillin-resistant S. aureus infections among patients in the emergency department.N Engl J Med. 2006; 355: 666-674Crossref PubMed Scopus (1948) Google Scholar The Moran paper contained an additional troubling statistic: 57% of the patients with CA-MRSA had been given an inappropriate antibiotic before seeking care at the ED, incontrovertible evidence that their previous physicians had neither considered the possibility of MRSA nor cultured the infections to check. “Convincing people to change their empiric therapy is hard,” acknowledged Katherine Heilpern, MD, chair of emergency medicine at Emory University School of Medicine and a member of EmergencyID Net who participated in Moran’s study. “You’re taught in medical school that a skin infection will be staph or strep, most likely staph, and you wave a little Keflex at it and it is taken care of. Now we’re on a merry-go-round of watching medicine change and watching this pathogen emerge.” Knowing that cephalosporins are inappropriate therapy unfortunately does not translate into knowing which drug or dose is the best replacement. CA-MRSA is generally held to be sensitive to trimethoprim-sulfamethoxazole, clindamycin, doxycycline and rifampin.29Strategies for Clinical Management of MRSA in the Community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention.http://cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdfDate: 2006Google Scholar But which drug is the first choice, what the regimen should be and whether it should be used in combination are currently more art than science—and likely to remain so, given that the drugs are long off-patent and unlikely to be the subject of pharmaceutical company research. To remedy that, the National Institutes of Health last year awarded two 5-year grants to several university teams to research off-patent drugs for CA-MRSA. The challenge will be defining optimal regimens before the bacteria acquires additional resistance: Some CA-MRSA isolates have shown either stable or inducible clindamycin resistance,30Brady J.M. Stemper M.E. Weigel A. et al.Sporadic “transitional” community-associated methicillin-resistant Staphylococcus aureus strains from health care facilities in the United States.J Clin Microbiol. 2007; 45: 2654-2661Crossref PubMed Scopus (18) Google Scholar, 31Moore Z.S. Jerris R.C. Hilinski J.A. High prevalence of inducible clindamycin resistance among Staphylococcus aureus isolates from patients with cystic fibrosis.J Cyst Fibros. 2007; Google Scholar and one report at the 2007 American College of Emergency Physicians Research Forum presented evidence of resistance to Bactrim.32Moriarity R. Trimethoprim-sulfamethoxazole resistance in community-acquired methicillin resistant staphylococcus aureus.Ann Emerg Med. 2007; 50: S57Abstract Full Text Full Text PDF Google Scholar And drug choice is not the biggest challenge of MRSA treatment; recognizing the infection comes first. “I know that if someone walked into our ED with suspected MRSA, a lot of our physicians would say: ‘This person doesn’t use drugs, hasn’t been in jail, doesn’t play on a football team–there’s no way this is MRSA,’” said Loren G. Miller, MD, MPH, an infectious disease specialist at the David Geffen School of Medicine at University of California-Los Angeles. “Maybe you could say that 10 years ago, but you can’t say it now.” The title of a paper Miller authored last year bluntly stated the new reality: “Clinical and Epidemiologic Characteristics Cannot Distinguish Community-Associated MRSA Infection from Methicillin-Sensitive S. Aureus Infection.” The paper, a prospective study of 180 adults with either resistant or susceptible S. aureus, found that patients were just as likely to be infected with MRSA whether or not they shared the traditional risk factors: prior health care exposure, injection drug use, incarceration, or pro sports, among others.33Miller L.G. Perdreau-Remington F. Bayer A.S. et al.Clinical and epidemiologic characteristics cannot distinguish community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureus infection: a prospective investigation.Clin Infect Dis. 2007; 44: 471-482Crossref PubMed Scopus (218) Google Scholar “The one-sentence take-home message is, Anybody can get MRSA—period,” Miller said. “If you walk into a clinic or an emergency department in 2007 with a skin infection with pus in it, it is MRSA unless proven otherwise.” The new prevalence of CA-MRSA poses additional challenges for ED staff. Hospital-acquired-MRSA became endemic in hospitals through simple failures in infection control; several studies in the past decade have demonstrated that EDs’ record of hand-washing is poor.34Meengs M.R. Giles B.K. Chisholm C.D. et al.Hand washing frequency in an emergency department.Ann Emerg Med. 1994; 23: 1307-1312Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 35Dorsey S.T. Cydulka R.K. Emerman C.L. Is handwashing teachable?: failure to improve handwashing behavior in an urban emergency department.Acad Emerg Med. 1996; 3: 360-365Crossref PubMed Scopus (58) Google Scholar, 36Larson E.L. Albrecht S. O’Keefe M. Hand hygiene behavior in a pediatric emergency department and a pediatric intensive care unit: comparison of use of 2 dispenser systems.Am J Crit Care. 2005; 14 (quiz 12): 304-1311PubMed Google Scholar The risks of poor hygiene in an ED are likely to be exacerbated not only by ED stress and crowding, but also by MRSA’s known ability to remain viable on hospital surfaces—in one study, for more than 12 days.37Huang R. Mehta S. Weed D. et al.Methicillin-resistant Staphylococcus aureus survival on hospital fomites.Infect Control Hosp Epidemiol. 2006; 27: 1267-1269Crossref PubMed Scopus (83) Google Scholar And if EDs become amplifiers of CA-MRSA, it may not only be patients who are at risk. Last year, a Garland, TX firefighter and emergency medical technician died of invasive MRSA,38Jacobsen S. Seeking cure to staph’s mystery: After firefighter dies, his wife asks: How could this happen?.Dallas Morning News. 2007Google Scholar and a Troy, NY firefighter/EMT was temporarily disabled by extensive soft tissue infection.39Tucker A. Spread of Rare Infection Sparks Concern.2007Google Scholar In 2005, this journal carried a report of an emergency medicine resident with recurrent MRSA infection that might have been occupationally acquired.40Storch J. Jacoby J.L. Heller M. Community-associated methicillin resistant Staphylococcus aureus in an emergency medicine resident: lessons learned.Ann Emerg Med. 2005; 46: 384-385Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar CA-MRSA “is here to stay,” Moran said, who hopes to repeat the EmergencyID Net study this year to see whether prevalence continues to increase or has plateaued. “It has become the new normal. There is something about these strains that gives them a survival advantage, and I don’t think we will see that go away.”