HAND/PERIPHERAL NERVE Methicillin-Resistant Staphylococcus aureus Infection in the Hand Bridget Harrison, M.D. Oded Ben-Amotz, M.D. Douglas M. Sammer, M.D. Dallas, Texas
Background: Methicillin-resistant Staphylococcus aureus has become an increasingly common cause of skin and soft-issue infections. The purpose of this study was to review and summarize the most recent literature on methicillin-resistant S. aureus infections of the hand. Methods: The English-language literature related to methicillin-resistant S. aureus infections of the hand was reviewed, and information related to the history, epidemiology, clinical presentation, and treatment of methicillin-resistant S. aureus infections of the hand was summarized. Results: Community-acquired methicillin-resistant S. aureus hand infections have increased rapidly in prevalence over the past two decades. The prevalence varies markedly around the world, but in the United States, communityacquired methicillin-resistant S. aureus now causes the majority of purulent hand infections. Conclusions: Purulent hand infections should be treated with surgical drainage. When antibiotics are indicated, empiric coverage for community-acquired methicillin-resistant S. aureus should be provided if local prevalence rates exceed 10 to 15 percent. (Plast. Reconstr. Surg. 135: 826, 2015.)
M
ethicillin-resistant Staphylococcus aureus has become an exceedingly common cause of infection, and has reached endemic proportions in many populations. It is believed that over 20 million people in the United States are colonized with methicillin-resistant S. aureus,1 and the prevalence of methicillin-resistant S. aureus in skin and soft-tissue infections continues to rise. Community-acquired methicillin-resistant S. aureus has recently emerged as the leading cause of purulent skin and soft-tissue infections in the hand. Methicillin-resistant S. aureus is particularly concerning not only because of its antibiotic resistance and rising prevalence but also because it is associated with worse outcomes compared with methicillin-sensitive S. aureus. Although new treatments and prevention strategies have been developed, methicillin-resistant S. aureus resistance patterns continue to evolve.
HISTORY Methicillin is a semisynthetic penicillin that was first introduced in 1959, and was specifically From the Department of Plastic Surgery, University of Texas Southwestern Medical Center. Received for publication August 7, 2014; accepted September 15, 2014. Copyright © 2015 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000952
826
designed to treat penicillin G–resistant staphylococcal infections, which had become a significant problem at the time.2,3 Almost immediately after its introduction, concerns arose about resistance to methicillin. By 1961, S. aureus bacteria exhibiting resistance to methicillin had been identified.4 At first, isolated clinical cases of methicillin-resistant S. aureus—typically, nosocomial infections— were reported. In 1968, a large hospital outbreak of methicillin-resistant S. aureus was reported at the Boston City Hospital.5 Since then, methicillinresistant S. aureus has continued to spread among hospitalized patients, and is typically associated with risk factors such as prolonged hospital admission, extensive antibiotic treatment, and longterm indwelling devices such as endotracheal tubes, central lines, or urinary catheters. This form of methicillin-resistant S. aureus remains a substantial source of morbidity and mortality in hospitalized patients, and is now known as hospital-acquired methicillin-resistant S. aureus. For many years, methicillin-resistant S. aureus was believed to be a problem that had been created in and that arose only in specific hospital settings.6 However, in 1981, the first report of a new strain of community-acquired methicillin-resistant Disclosure: The authors have no financial interest to declare in relation to the content of this article.
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Volume 135, Number 3 • Methicillin-Resistant S. aureus S. aureus challenged this notion.6 It was initially thought that resistance had spread from hospitals to the community. However, subsequent studies have demonstrated that the resistance in community-acquired methicillin-resistant S. aureus evolved through a separate and novel mechanism.7 Community-acquired methicillin-resistant S. aureus has had a remarkably rapid rise in prevalence, and has reached endemic proportions in many populations. Community-acquired methicillin-resistant S. aureus is distinguished from hospital-acquired methicillin-resistant S. aureus by a diagnosis of methicillin-resistant S. aureus in the outpatient setting or within 48 hours after admission to the hospital in a patient with no history of methicillin-resistant S. aureus infection, and no history in the past year of hospitalization, dialysis, surgery, or admission to a nursing home or skilled nursing facility. Community-acquired methicillin-resistant S. aureus is different from hospital-acquired methicillin-resistant S. aureus in terms of its epidemiology, resistance mechanism, and clinical presentation.6 Importantly, community-acquired methicillin-resistant S. aureus has recently emerged as a leading cause of skin and soft-tissue infections in the hand.
EPIDEMIOLOGY Numerous studies performed over the last two decades show a dramatic increase in the prevalence of community-acquired methicillin-resistant S. aureus hand infections. It should be noted that these studies evaluated culture-positive infections of the hand, meaning that most of the cases studied were purulent infections. Therefore, the prevalence results may not (and probably do not) apply to nonpurulent hand infections such as cellulitis. One of the most dramatic studies was performed in Seattle, Washington, and evaluated patients who had been treated in the operating room for purulent hand infections between 1997 and 2007. This study demonstrated an initial 8 percent methicillin-resistant S. aureus prevalence in 1997, which increased to 58 percent by 2007.8 Multiple other hospital-specific studies of prevalence rates in the late 1990s and 2000s demonstrate very similar rapid increases in community-acquired methicillin-resistant S. aureus prevalence.9–11 Furthermore, these and other studies confirm that community-acquired methicillinresistant S. aureus not only has become the most prevalent cause of purulent skin and soft-tissue infections of the hand, but now causes the majority of these infections.9,11–16
Community-acquired methicillin-resistant S. aureus–associated skin and soft-tissue infections have also become more prevalent in the pediatric population. A 2012 study performed at a dedicated pediatric emergency department demonstrated that the prevalence of community-acquired methicillin-resistant S. aureus in skin and soft-tissue infections of various anatomical sites had doubled between 2003 and 2008, causing up to 42 percent of culture-positive infections.12 Another study from 2012 specifically evaluated skin and soft-tissue infections of the hand in the pediatric population, and demonstrated a 30 percent prevalence of community-acquired methicillin-resistant S. aureus in healthy patients younger than 15 years.17 Although these prevalence rates are not as high as in the adult population, it appears that community-acquired methicillin-resistant S. aureus is becoming a more common cause of skin and softtissue infections in children as well. Certain risk factors have been historically associated with increased rates of communityacquired methicillin-resistant S. aureus infection in general. These include recent antibiotic use, contaminated surfaces, breaks in skin integrity, shared clothing or sports equipment, and intravenous drug use. Subpopulations thought to be at risk for community-acquired methicillin-resistant S. aureus include those in crowded living conditions such as day-care, the homeless, inmates, athletes, and military personnel.18 In the hand specifically, a history of intravenous drug use has been identified as a positive risk factor for community-acquired methicillin-resistant S. aureus infection in two of three studies that evaluated this issue.8,14,16 However, diabetes, homelessness, and immunocompromised conditions have not been clearly identified as risk factors for communityacquired methicillin-resistant S. aureus infections of the hand.9,12 Furthermore, a 2009 study demonstrated that community-acquired methicillinresistant S. aureus was more common in healthy populations than in immunocompromised or diabetic patients.19 In the pediatric population, patients tend to be healthy, and immunocompromise has not been shown to be a risk factor.3 Community-acquired methicillin-resistant S. aureus infection rates vary globally as well. Although the above percentages are representative of infection rates in the United States, they generally exceed levels in other countries. A review of patients treated for hand infections in New Zealand found only a 7 percent rate of community-acquired methicillin-resistant S. aureus.20 A similar study in Scotland demonstrated a rate
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Plastic and Reconstructive Surgery • March 2015 of less than 1 percent.21 This is clinically relevant, because the Centers for Disease Control and Prevention recommends empiric coverage for methicillin-resistant S. aureus only if the local prevalence rate exceeds 10 to 15 percent.22
MICROBIOLOGY Acquiring antibiotic resistance is necessary for microbial survival in the current era of antibiotic overuse. Staphylococcal resistance to penicillins occurs through expression of an enzyme, β-lactamase, which hydrolyzes the β-lactam ring that forms the foundation of penicillins. Methicillin, as noted above, is a semisynthetic penicillin, which is unaffected by β-lactamases secreted by staphylococcal species. Resistance to methicillin occurs through a different mechanism, which represents a change in the bacterial cell wall. Penicillins, including methicillin, work by attaching to a protein in the bacterial cell wall called penicillin binding protein 2. This protein normally functions within the cell wall to cross-link cell wall building blocks or precursors. Penicillins bind to this protein and thereby inhibit its function, resulting in a weakened cell wall and bacterial destruction. In methicillin-resistant S. aureus, the mecA gene codes for a mutant penicillin binding protein-2A, which is resistant to
binding by penicillins and cephalosporins. This gene is located on a portion of the chromosome called the staphylococcal chromosomal cassette (SCCmec), and is highly transmissible by means of plasmid transfer (Fig. 1). Community-acquired methicillin-resistant S. aureus contains SCCmec subtypes that are distinct from those carried in hospital-acquired methicillin-resistant S. aureus. Of note, the subtypes of SCCmec (IV and V) most commonly carried in community-acquired methicillin-resistant S. aureus, confer resistance to fewer antibiotic types than the SCCmec subtypes typically carried by hospital-acquired methicillin-resistant S. aureus. Certain strains of community-acquired methicillin-resistant S. aureus, such as the USA300 strain, which is common in the United States, also carries a virulence factor, or gene, that codes for a protein that leads to increased virulence. This factor is Panton-Valentine leukocidin, a protein that is toxic to host phagocytes, by forming pores in leukocytes and facilitating their destruction.6,19 To summarize, community-acquired methicillin-resistant S. aureus resistance is conferred by a slightly different chromosomal element than hospital-acquired methicillin-resistant S. aureus, and typically has less resistance to certain types of antibiotics. In addition, community-acquired methicillin-resistant S. aureus often contains other factors that may make it more clinically virulent.
Fig. 1. The SCCmec chromosomal cassette containing the MecA gene is transferred by plasmid into the bacterium. The MecA gene codes for the production of abnormal penicillin binding proteins (PBP2A) which are resistant to binding by penicillins (PCN).
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Volume 135, Number 3 • Methicillin-Resistant S. aureus CLINICAL PRESENTATION Community-acquired methicillin-resistant S. aureus has a predilection for skin and soft-tissue infections, and frequently presents in the hand. Infections such as cellulitis, abscess, paronychia, felon, and tenosynovitis can be caused by methicillin-resistant S. aureus.23 Methicillin-resistant S. aureus has also been implicated in cases of blistering dactylitis,24 septic arthritis,25 and osteomyelitis. Methicillin-resistant S. aureus cannot be diagnosed clinically, although several clinical clues may point to its presence. Painful lesions with a black center or central eschar overlying a purulent collection are common,26 and the patient may report a history of a spider bite. Isolated cellulitis is more likely to be another type of pathogen, such as Streptococcus pyogenes. The presence of a pustule, boil, or abscess with minimal surrounding erythema suggests a higher likelihood of S. aureus or community-acquired methicillin-resistant S. aureus. A high index of suspicion should also be maintained in patients with recurrent abscesses, as methicillin-resistant S. aureus colonization may result in recurrent infections.27
TREATMENT Despite the recent increase in methicillinresistant S. aureus prevalence, the treatment of an abscess has not changed. The primary treatment for a subcutaneous abscess, felon, or flexor tenosynovitis requires incision, drainage, and irrigation. For simple abscesses, incision and drainage alone are likely adequate. The Infectious Diseases Society of America recommends antibiotic therapy for abscesses associated with severe or extensive disease, rapid progression, signs and symptoms of systemic illness, associated comorbidities or immunosuppression, extremes of age, and abscesses in areas difficult to drain. These guidelines include the hand in areas considered difficult to drain, suggesting that infections of the hand should be
treated with antibiotics in conjunction with surgical drainage.28 Because of the rise in prevalence of methicillin-resistant S. aureus, the Infectious Diseases Society of America now recommends empiric therapy for community-acquired methicillin-resistant S. aureus in patients with purulent cellulitis, major abscesses, deep soft-tissue infections, and traumatic wound infections. Outpatient empiric community-acquired methicillin-resistant S. aureus coverage options include clindamycin, trimethoprim-sulfamethoxazole, a tetracycline (doxycycline or minocycline), and linezolid. Clindamycin resistance is increasing.29,30 However, it does have the advantage of high bioavailability, so that oral administration has approximately 90 percent of the availability of parenteral administration. Doxycycline also has high bioavailability, although resistance to doxycycline and minocycline has also been documented.31 It is therefore prudent to reevaluate patients sent home on oral antibiotics within 24 to 48 hours to verify appropriate response, and to follow culture sensitivities and tailor antibiotics. Resistance patterns can vary between communities and hospitals, and individual hospital resistance data can be helpful when selecting an empiric antibiotic. Hospitalized patients with methicillin-resistant S. aureus infections can be treated with intravenous vancomycin, oral or intravenous linezolid, daptomycin, telavancin, or clindamycin (Table 1). The duration of treatment is dependent on clinical response.
CONCLUSIONS Community-acquired methicillin-resistant S. aureus is the most common cause of culture-positive hand infections in the United States, and a very high index of suspicion should be maintained for the presence of methicillin-resistant S. aureus as a causative organism in both adult and pediatric outpatient populations. Clinical clues include purulence (pustule, boil, and abscess) with minimal associated
Table 1. Summary of Antibiotics Used to Treat Methicillin-Resistant S. aureus Antibiotic
Route of Administration
Erythromycin Clindamycin Linezolid Daptomycin Vancomycin Teicoplanin
PO/IV PO/IV PO/IV IV IV IV
Doxycycline Tigecycline Rifampin Bactrim
PO IV PO/IV PO
Benefits Good activity against Gram-positive organisms Good bone penetration Good bioavailability, low resistance Once-daily administration Good experience with use Less nephrotoxic than vancomycin, daily administration Once-daily administration Covers some Gram-negative organisms Good tissue penetration Twice-daily oral administration
Side Effects GI side effects, frequent administration Risk of Clostridium difficile diarrhea Hematologic side effects Nephrotoxicity requires monitoring GI side effects GI side effects Cannot be used alone GI side effects, Stevens-Johnson syndrome
PO, oral; IV, intravenous; GI, gastrointestinal.
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Plastic and Reconstructive Surgery • March 2015 cellulitis. In the United States, and in other locations with a high incidence of community-acquired methicillin-resistant S. aureus infection, empiric coverage for community-acquired methicillin-resistant S. aureus should be provided when antibiotics are indicated. Local community-acquired methicillinresistant S. aureus resistance patterns should be evaluated to help guide empiric antibiotic coverage. Because of changing resistance patterns, close clinical follow-up and evaluation of culture sensitivities should be performed. Douglas M. Sammer, M.D. Department of Plastic Surgery University of Texas Southwestern Medical Center 1801 Inwood Road Dallas, Texas 75390 [email protected]
REFERENCES 1. Hill C, King T, Day R. A strategy to reduce MRSA colonization of stethoscopes. J Hosp Infect. 2006;62:122–123. 2. Douthwaite AH, Trafford JA. A new synthetic penicillin. BMJ 1960;2:687–690. 3. Douthwaite AH. The new penicillins, with special reference to ‘broxil’. Practitioner 1960;184:793–798. 4. Jevons MP, Coe AW, Parker MT. Methicillin resistance in staphylococci. Lancet 1963;1:904–907. 5. Barrett FF, McGehee RF Jr, Finland M. Methicillin-resistant Staphylococcus aureus at Boston City Hospital: Bacteriologic and epidemiologic observations. N Engl J Med. 1968;279:441–448. 6. Pottinger PS. Methicillin-resistant Staphylococcus aureus infections. Med Clin North Am. 2013;97:601–619, x. 7. Crum NF, Lee RU, Thornton SA, et al. Fifteen-year study of the changing epidemiology of methicillin-resistant Staphylococcus aureus. Am J Med. 2006;119:943–951. 8. Imahara SD, Friedrich JB. Community-acquired methicillinresistant Staphylococcus aureus in surgically treated hand infections. J Hand Surg Am. 2010;35:97–103. 9. Bach HG, Steffin B, Chhadia AM, Kovachevich R, Gonzalez MH. Community-associated methicillin-resistant Staphylococcus aureus hand infections in an urban setting. J Hand Surg Am. 2007;32:380–383. 10. Nourbakhsh A, Papafragkou S, Dever LL, Capo J, Tan V. Stratification of the risk factors of community-acquired methicillin-resistant Staphylococcus aureus hand infection. J Hand Surg Am. 2010;35:1135–1141. 11. LeBlanc DM, Reece EM, Horton JB, Janis JE. Increasing incidence of methicillin-resistant Staphylococcus aureus in hand infections: A 3-year county hospital experience. Plast Reconstr Surg. 2007;119:935–940. 12. Karamatsu ML, Thorp AW, Brown L. Changes in communityassociated methicillin-resistant Staphylococcus aureus skin and soft tissue infections presenting to the pediatric emergency department: Comparing 2003 to 2008. Pediatr Emerg Care 2012;28:131–135. 13. Wilson PC, Rinker B. The incidence of methicillin-resistant Staphylococcus aureus in community-acquired hand infections. Ann Plast Surg. 2009;62:513–516. 14. O’Malley M, Fowler J, Ilyas AM. Community-acquired methicillinresistant Staphylococcus aureus infections of the hand: Prevalence and timeliness of treatment. J Hand Surg Am. 2009;34:504–508.
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15. Fowler JR, Greenhill D, Schaffer AA, Thoder JJ, Ilyas AM. Evolving incidence of MRSA in urban hand infections. Orthopedics 2013;36:796–800. 16. Fowler JR, Ilyas AM. Epidemiology of adult acute hand infections at an urban medical center. J Hand Surg Am. 2013;38:1189–1193. 17. Chung MT, Wilson P, Rinker B. Community-acquired methicillin-resistant Staphylococcus aureus hand infections in the pediatric population. J Hand Surg Am. 2012;37:326–331. 18. Downs DJ, Wongworawat MD, Gregorius SF. Timeliness of appropriate antibiotics in hand infections. Clin Orthop Relat Res. 2007;461:17–19. 19. Reygaert W. Methicillin-resistant Staphylococcus aureus (MRSA): Molecular aspects of antimicrobial resistance and virulence. Clin Lab Sci. 2009;22:115–119. 20. Buchanan D, Heiss-Dunlop W, Mathy JA. Community acquired methicillin resistant Staphylococcus aureus hand infections: A South Pacific perspective. Characteristics and implications for antibiotic coverage. Hand Surg. 2012;17:317–324. 21. Hassan S, Gashau W, Balchin L, Orange G, Wilmshurst A. Incidence of community-acquired methicillin resistant Staphylococcus aureus hand infections in Tayside, Scotland: A guide to appropriate antimicrobial prescribing. J Hand Surg Eur Vol. 2011;36:226–229. 22. Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA;Jernigan DB; Centers for Disease Control and Prevention–Convened Experts’ Meeting on Management of MRSA in the Community. Strategies for clinical management of MRSA in the community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/mrsa/pdf/MRSA-Strategies-ExpMtg Summary-2006.pdf. Accessed January 28, 3015. 23. McDonald LS, Bavaro MF, Hofmeister EP, Kroonen LT. Hand infections. J Hand Surg Am. 2011;36:1403–1412. 24. Fretzayas A, Moustaki M, Tsagris V, Brozou T, Nicolaidou P. MRSA blistering distal dactylitis and review of reported cases. Pediatr Dermatol. 2011;28:433–435. 25. Thangarajah T, Neal TJ, Kennedy TD. An unexpected diagnosis of methicillin-resistant Staphylococcus aureus septic arthritis. Orthop Rev (Pavia) 2009;1:e13. 26. Daum RS. Clinical practice: Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 2007;357:380–390. 27. Wearn CM, Breuning EE, Chester DL. Recurrent primary abscesses in the hand: Consider Panton-Valentine leukocidinpositive Staphylococcus aureus. J Hand Surg Eur Vol. March 5, 2013; [Epub ahead of print]. 28. Liu C, Bayer A, Cosgrove SE, et al.; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:e18–e55. 29. Alexander AJ, Richardson SE, Sharma A, Campisi P. The increasing prevalence of clindamycin resistance in Staphylococcus aureus isolates in children with head and neck abscesses. Can J Infect Dis Med Microbiol. 2011;22:49–51. 30. Cadena J, Sreeramoju P, Nair S, Henao-Martinez A, Jorgensen J, Patterson JE. Clindamycin-resistant methicillinresistant Staphylococcus aureus: Epidemiologic and molecular characteristics and associated clinical factors. Diagn Microbiol Infect Dis. 2012;74:16–21. 31. Ruhe JJ, Monson T, Bradsher RW, Menon A. Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus infections: Case series and review of the literature. Clin Infect Dis. 2005;40:1429–1434.
Background: Methicillin-resistant Staphylococcus aureus has become an increasingly common cause of skin and soft-issue infections. The purpose of this study was to review and summarize the most recent literature on methicillin-resistant S. aureus infections of the hand. Methods: The English-language literature related to methicillin-resistant S. aureus infections of the hand was reviewed, and information related to the history, epidemiology, clinical presentation, and treatment of methicillin-resistant S. aureus infections of the hand was summarized. Results: Community-acquired methicillin-resistant S. aureus hand infections have increased rapidly in prevalence over the past two decades. The prevalence varies markedly around the world, but in the United States, communityacquired methicillin-resistant S. aureus now causes the majority of purulent hand infections. Conclusions: Purulent hand infections should be treated with surgical drainage. When antibiotics are indicated, empiric coverage for community-acquired methicillin-resistant S. aureus should be provided if local prevalence rates exceed 10 to 15 percent. (Plast. Reconstr. Surg. 135: 826, 2015.)
M
ethicillin-resistant Staphylococcus aureus has become an exceedingly common cause of infection, and has reached endemic proportions in many populations. It is believed that over 20 million people in the United States are colonized with methicillin-resistant S. aureus,1 and the prevalence of methicillin-resistant S. aureus in skin and soft-tissue infections continues to rise. Community-acquired methicillin-resistant S. aureus has recently emerged as the leading cause of purulent skin and soft-tissue infections in the hand. Methicillin-resistant S. aureus is particularly concerning not only because of its antibiotic resistance and rising prevalence but also because it is associated with worse outcomes compared with methicillin-sensitive S. aureus. Although new treatments and prevention strategies have been developed, methicillin-resistant S. aureus resistance patterns continue to evolve.
HISTORY Methicillin is a semisynthetic penicillin that was first introduced in 1959, and was specifically From the Department of Plastic Surgery, University of Texas Southwestern Medical Center. Received for publication August 7, 2014; accepted September 15, 2014. Copyright © 2015 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000952
826
designed to treat penicillin G–resistant staphylococcal infections, which had become a significant problem at the time.2,3 Almost immediately after its introduction, concerns arose about resistance to methicillin. By 1961, S. aureus bacteria exhibiting resistance to methicillin had been identified.4 At first, isolated clinical cases of methicillin-resistant S. aureus—typically, nosocomial infections— were reported. In 1968, a large hospital outbreak of methicillin-resistant S. aureus was reported at the Boston City Hospital.5 Since then, methicillinresistant S. aureus has continued to spread among hospitalized patients, and is typically associated with risk factors such as prolonged hospital admission, extensive antibiotic treatment, and longterm indwelling devices such as endotracheal tubes, central lines, or urinary catheters. This form of methicillin-resistant S. aureus remains a substantial source of morbidity and mortality in hospitalized patients, and is now known as hospital-acquired methicillin-resistant S. aureus. For many years, methicillin-resistant S. aureus was believed to be a problem that had been created in and that arose only in specific hospital settings.6 However, in 1981, the first report of a new strain of community-acquired methicillin-resistant Disclosure: The authors have no financial interest to declare in relation to the content of this article.
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Volume 135, Number 3 • Methicillin-Resistant S. aureus S. aureus challenged this notion.6 It was initially thought that resistance had spread from hospitals to the community. However, subsequent studies have demonstrated that the resistance in community-acquired methicillin-resistant S. aureus evolved through a separate and novel mechanism.7 Community-acquired methicillin-resistant S. aureus has had a remarkably rapid rise in prevalence, and has reached endemic proportions in many populations. Community-acquired methicillin-resistant S. aureus is distinguished from hospital-acquired methicillin-resistant S. aureus by a diagnosis of methicillin-resistant S. aureus in the outpatient setting or within 48 hours after admission to the hospital in a patient with no history of methicillin-resistant S. aureus infection, and no history in the past year of hospitalization, dialysis, surgery, or admission to a nursing home or skilled nursing facility. Community-acquired methicillin-resistant S. aureus is different from hospital-acquired methicillin-resistant S. aureus in terms of its epidemiology, resistance mechanism, and clinical presentation.6 Importantly, community-acquired methicillin-resistant S. aureus has recently emerged as a leading cause of skin and soft-tissue infections in the hand.
EPIDEMIOLOGY Numerous studies performed over the last two decades show a dramatic increase in the prevalence of community-acquired methicillin-resistant S. aureus hand infections. It should be noted that these studies evaluated culture-positive infections of the hand, meaning that most of the cases studied were purulent infections. Therefore, the prevalence results may not (and probably do not) apply to nonpurulent hand infections such as cellulitis. One of the most dramatic studies was performed in Seattle, Washington, and evaluated patients who had been treated in the operating room for purulent hand infections between 1997 and 2007. This study demonstrated an initial 8 percent methicillin-resistant S. aureus prevalence in 1997, which increased to 58 percent by 2007.8 Multiple other hospital-specific studies of prevalence rates in the late 1990s and 2000s demonstrate very similar rapid increases in community-acquired methicillin-resistant S. aureus prevalence.9–11 Furthermore, these and other studies confirm that community-acquired methicillinresistant S. aureus not only has become the most prevalent cause of purulent skin and soft-tissue infections of the hand, but now causes the majority of these infections.9,11–16
Community-acquired methicillin-resistant S. aureus–associated skin and soft-tissue infections have also become more prevalent in the pediatric population. A 2012 study performed at a dedicated pediatric emergency department demonstrated that the prevalence of community-acquired methicillin-resistant S. aureus in skin and soft-tissue infections of various anatomical sites had doubled between 2003 and 2008, causing up to 42 percent of culture-positive infections.12 Another study from 2012 specifically evaluated skin and soft-tissue infections of the hand in the pediatric population, and demonstrated a 30 percent prevalence of community-acquired methicillin-resistant S. aureus in healthy patients younger than 15 years.17 Although these prevalence rates are not as high as in the adult population, it appears that community-acquired methicillin-resistant S. aureus is becoming a more common cause of skin and softtissue infections in children as well. Certain risk factors have been historically associated with increased rates of communityacquired methicillin-resistant S. aureus infection in general. These include recent antibiotic use, contaminated surfaces, breaks in skin integrity, shared clothing or sports equipment, and intravenous drug use. Subpopulations thought to be at risk for community-acquired methicillin-resistant S. aureus include those in crowded living conditions such as day-care, the homeless, inmates, athletes, and military personnel.18 In the hand specifically, a history of intravenous drug use has been identified as a positive risk factor for community-acquired methicillin-resistant S. aureus infection in two of three studies that evaluated this issue.8,14,16 However, diabetes, homelessness, and immunocompromised conditions have not been clearly identified as risk factors for communityacquired methicillin-resistant S. aureus infections of the hand.9,12 Furthermore, a 2009 study demonstrated that community-acquired methicillinresistant S. aureus was more common in healthy populations than in immunocompromised or diabetic patients.19 In the pediatric population, patients tend to be healthy, and immunocompromise has not been shown to be a risk factor.3 Community-acquired methicillin-resistant S. aureus infection rates vary globally as well. Although the above percentages are representative of infection rates in the United States, they generally exceed levels in other countries. A review of patients treated for hand infections in New Zealand found only a 7 percent rate of community-acquired methicillin-resistant S. aureus.20 A similar study in Scotland demonstrated a rate
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Plastic and Reconstructive Surgery • March 2015 of less than 1 percent.21 This is clinically relevant, because the Centers for Disease Control and Prevention recommends empiric coverage for methicillin-resistant S. aureus only if the local prevalence rate exceeds 10 to 15 percent.22
MICROBIOLOGY Acquiring antibiotic resistance is necessary for microbial survival in the current era of antibiotic overuse. Staphylococcal resistance to penicillins occurs through expression of an enzyme, β-lactamase, which hydrolyzes the β-lactam ring that forms the foundation of penicillins. Methicillin, as noted above, is a semisynthetic penicillin, which is unaffected by β-lactamases secreted by staphylococcal species. Resistance to methicillin occurs through a different mechanism, which represents a change in the bacterial cell wall. Penicillins, including methicillin, work by attaching to a protein in the bacterial cell wall called penicillin binding protein 2. This protein normally functions within the cell wall to cross-link cell wall building blocks or precursors. Penicillins bind to this protein and thereby inhibit its function, resulting in a weakened cell wall and bacterial destruction. In methicillin-resistant S. aureus, the mecA gene codes for a mutant penicillin binding protein-2A, which is resistant to
binding by penicillins and cephalosporins. This gene is located on a portion of the chromosome called the staphylococcal chromosomal cassette (SCCmec), and is highly transmissible by means of plasmid transfer (Fig. 1). Community-acquired methicillin-resistant S. aureus contains SCCmec subtypes that are distinct from those carried in hospital-acquired methicillin-resistant S. aureus. Of note, the subtypes of SCCmec (IV and V) most commonly carried in community-acquired methicillin-resistant S. aureus, confer resistance to fewer antibiotic types than the SCCmec subtypes typically carried by hospital-acquired methicillin-resistant S. aureus. Certain strains of community-acquired methicillin-resistant S. aureus, such as the USA300 strain, which is common in the United States, also carries a virulence factor, or gene, that codes for a protein that leads to increased virulence. This factor is Panton-Valentine leukocidin, a protein that is toxic to host phagocytes, by forming pores in leukocytes and facilitating their destruction.6,19 To summarize, community-acquired methicillin-resistant S. aureus resistance is conferred by a slightly different chromosomal element than hospital-acquired methicillin-resistant S. aureus, and typically has less resistance to certain types of antibiotics. In addition, community-acquired methicillin-resistant S. aureus often contains other factors that may make it more clinically virulent.
Fig. 1. The SCCmec chromosomal cassette containing the MecA gene is transferred by plasmid into the bacterium. The MecA gene codes for the production of abnormal penicillin binding proteins (PBP2A) which are resistant to binding by penicillins (PCN).
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Volume 135, Number 3 • Methicillin-Resistant S. aureus CLINICAL PRESENTATION Community-acquired methicillin-resistant S. aureus has a predilection for skin and soft-tissue infections, and frequently presents in the hand. Infections such as cellulitis, abscess, paronychia, felon, and tenosynovitis can be caused by methicillin-resistant S. aureus.23 Methicillin-resistant S. aureus has also been implicated in cases of blistering dactylitis,24 septic arthritis,25 and osteomyelitis. Methicillin-resistant S. aureus cannot be diagnosed clinically, although several clinical clues may point to its presence. Painful lesions with a black center or central eschar overlying a purulent collection are common,26 and the patient may report a history of a spider bite. Isolated cellulitis is more likely to be another type of pathogen, such as Streptococcus pyogenes. The presence of a pustule, boil, or abscess with minimal surrounding erythema suggests a higher likelihood of S. aureus or community-acquired methicillin-resistant S. aureus. A high index of suspicion should also be maintained in patients with recurrent abscesses, as methicillin-resistant S. aureus colonization may result in recurrent infections.27
TREATMENT Despite the recent increase in methicillinresistant S. aureus prevalence, the treatment of an abscess has not changed. The primary treatment for a subcutaneous abscess, felon, or flexor tenosynovitis requires incision, drainage, and irrigation. For simple abscesses, incision and drainage alone are likely adequate. The Infectious Diseases Society of America recommends antibiotic therapy for abscesses associated with severe or extensive disease, rapid progression, signs and symptoms of systemic illness, associated comorbidities or immunosuppression, extremes of age, and abscesses in areas difficult to drain. These guidelines include the hand in areas considered difficult to drain, suggesting that infections of the hand should be
treated with antibiotics in conjunction with surgical drainage.28 Because of the rise in prevalence of methicillin-resistant S. aureus, the Infectious Diseases Society of America now recommends empiric therapy for community-acquired methicillin-resistant S. aureus in patients with purulent cellulitis, major abscesses, deep soft-tissue infections, and traumatic wound infections. Outpatient empiric community-acquired methicillin-resistant S. aureus coverage options include clindamycin, trimethoprim-sulfamethoxazole, a tetracycline (doxycycline or minocycline), and linezolid. Clindamycin resistance is increasing.29,30 However, it does have the advantage of high bioavailability, so that oral administration has approximately 90 percent of the availability of parenteral administration. Doxycycline also has high bioavailability, although resistance to doxycycline and minocycline has also been documented.31 It is therefore prudent to reevaluate patients sent home on oral antibiotics within 24 to 48 hours to verify appropriate response, and to follow culture sensitivities and tailor antibiotics. Resistance patterns can vary between communities and hospitals, and individual hospital resistance data can be helpful when selecting an empiric antibiotic. Hospitalized patients with methicillin-resistant S. aureus infections can be treated with intravenous vancomycin, oral or intravenous linezolid, daptomycin, telavancin, or clindamycin (Table 1). The duration of treatment is dependent on clinical response.
CONCLUSIONS Community-acquired methicillin-resistant S. aureus is the most common cause of culture-positive hand infections in the United States, and a very high index of suspicion should be maintained for the presence of methicillin-resistant S. aureus as a causative organism in both adult and pediatric outpatient populations. Clinical clues include purulence (pustule, boil, and abscess) with minimal associated
Table 1. Summary of Antibiotics Used to Treat Methicillin-Resistant S. aureus Antibiotic
Route of Administration
Erythromycin Clindamycin Linezolid Daptomycin Vancomycin Teicoplanin
PO/IV PO/IV PO/IV IV IV IV
Doxycycline Tigecycline Rifampin Bactrim
PO IV PO/IV PO
Benefits Good activity against Gram-positive organisms Good bone penetration Good bioavailability, low resistance Once-daily administration Good experience with use Less nephrotoxic than vancomycin, daily administration Once-daily administration Covers some Gram-negative organisms Good tissue penetration Twice-daily oral administration
Side Effects GI side effects, frequent administration Risk of Clostridium difficile diarrhea Hematologic side effects Nephrotoxicity requires monitoring GI side effects GI side effects Cannot be used alone GI side effects, Stevens-Johnson syndrome
PO, oral; IV, intravenous; GI, gastrointestinal.
829
Plastic and Reconstructive Surgery • March 2015 cellulitis. In the United States, and in other locations with a high incidence of community-acquired methicillin-resistant S. aureus infection, empiric coverage for community-acquired methicillin-resistant S. aureus should be provided when antibiotics are indicated. Local community-acquired methicillinresistant S. aureus resistance patterns should be evaluated to help guide empiric antibiotic coverage. Because of changing resistance patterns, close clinical follow-up and evaluation of culture sensitivities should be performed. Douglas M. Sammer, M.D. Department of Plastic Surgery University of Texas Southwestern Medical Center 1801 Inwood Road Dallas, Texas 75390 [email protected]
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