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Cir034 285.292

Clinical Practice Guidelines by the InfectiousDiseases Society of America for the Treatment ofMethicillin-Resistant Staphylococcus aureusInfections in Adults and Children: ExecutiveSummary Catherine Liu,1 Arnold Bayer,3,5 Sara E. Cosgrove,6 Robert S. Daum,7 Scott K. Fridkin,8 Rachel J. Gorwitz,9Sheldon L. Kaplan,10 Adolf W. Karchmer,11 Donald P. Levine,12 Barbara E. Murray,14 Michael J. Rybak,12,13 DavidA. Talan,4,5 and Henry F. Chambers1,2 1Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California; 2Division of Infectious Diseases, San Francisco General Hospital, San Francisco, CA, 3Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, 4Divisions of EmergencyMedicine and Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA; 5Department of Medicine, David Geffen School of Medicine at Universityof California Los Angeles; 6Division of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland; 7Department of Pediatrics, Sectionof Infectious Diseases, University of Chicago, Chicago, Illinois; 8,9Division of Healthcare Quality Promotion, Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; 10Department of Pediatrics, Section of Infectious Diseases, Baylor College ofMedicine, Houston, Texas; 11Division of Infectious Diseases, Beth Israel Deaconess Medicine Center, Harvard Medical School, Boston, Massachusetts;12 Department of Medicine, Division of Infectious Diseases, Wayne State University, Detroit Receiving Hospital and University Health Center, Detroit,Michigan; 13Deparment of Pharmacy Practice, Wayne State University, Detroit Michigan; and 14Division of Infectious Diseases and Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Medical School, Houston, Texas Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus(MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). Theguidelines are intended for use by health care providers who care for adult and pediatric patients with MRSAinfections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSAdisease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone andjoint infections, and central nervous system (CNS) infections. Recommendations are provided regardingvancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibilityto vancomycin, and vancomycin treatment failures.
EXECUTIVE SUMMARY treatment of MRSA infections. The primary objective ofthese guidelines is to provide recommendations on the MRSA is a significant cause of both health care–associated management of some of the most common clinical syn- and community-associated infections. This document dromes encountered by adult and pediatric clinicians who constitutes the first guidelines of the IDSA on the care for patients with MRSA infections. The guidelinesaddress issues related to the use of vancomycin therapy inthe treatment of MRSA infections, including dosing and Received 28 October 2010; accepted 17 November 2010.
monitoring, current limitations of susceptibility testing, Correspondence: Catherine Liu, MD, Dept of Medicine, Div of Infectious Diseases, University of California–San Francisco, San Francisco, California, 94102 and the use of alternate therapies for those patients with vancomycin treatment failure and infection due to strains Clinical Infectious Diseases with reduced susceptibility to vancomycin. The guidelines Ó The Author 2011. Published by Oxford University Press on behalf of theInfectious Diseases Society of America. All rights reserved. For Permissions, do not discuss active surveillance testing or other MRSA infection–prevention strategies in health care set- tings, which are addressed in previously published MRSA Treatment Guidelines d CID 2011:52 (1 February) d 285 guidelines [1, 2]. Each section of the guidelines begins with a tetracycline (doxycycline or minocycline) (A-II), and linezolid a specific clinical question and is followed by numbered (A-II). If coverage for both b-hemolytic streptococci and recommendations and a summary of the most-relevant evidence in support of the recommendations. Areas of controversy in clindamycin alone (A-II) or TMP-SMX or a tetracycline in which data are limited or conflicting and where additional re- combination with a b-lactam (eg, amoxicillin) (A-II) or linezolid search is needed are indicated throughout the document and are alone (A-II).
highlighted in the Research Gaps section. The key recom- The use of rifampin as a single agent or as adjunctive mendations are summarized below in the Executive Summary; therapy for the treatment of SSTI is not recommended (A-III).
each topic is discussed in greater detail within the main body of For hospitalized patients with complicated SSTI (cSSTI; the guidelines.
defined as patients with deeper soft-tissue infections, surgical/ Please note that specific recommendations on vancomycin traumatic wound infection, major abscesses, cellulitis, and dosing and monitoring are not discussed in the sections for each infected ulcers and burns), in addition to surgical debridement clinical syndrome but are collectively addressed in detail in Section VIII.
MRSA should be considered pending culture data. Optionsinclude the following: intravenous (IV) vancomycin (A-I), I. What is the management of skin and soft-tissue infections oral (PO) or IV linezolid 600 mg twice daily (A-I), (SSTIs) in the era of community-associated MRSA (CA-MRSA)? daptomycin 4 mg/kg/dose IV once daily (A-I), telavancin 10 mg/kg/dose IV once daily (A-I), and clindamycin 600 mgIV or PO 3 times a day (A-III). A b-lactam antibiotic (eg, For a cutaneous abscess, incision and drainage is the cefazolin) may be considered in hospitalized patients with primary treatment (A-II). For simple abscesses or boils, nonpurulent cellulitis with modification to MRSA-active incision and drainage alone is likely to be adequate, but therapy if there is no clinical response (A-II). Seven to 14 additional data are needed to further define the role of days of therapy is recommended but should be individualized antibiotics, if any, in this setting.
on the basis of the patient's clinical response.
Antibiotic therapy is recommended for abscesses associated Cultures from abscesses and other purulent SSTIs are with the following conditions: severe or extensive disease (eg, recommended in patients treated with antibiotic therapy, involving multiple sites of infection) or rapid progression in patients with severe local infection or signs of systemic illness, presence of associated cellulitis, signs and symptoms of systemic patients who have not responded adequately to initial treatment, and if there is concern for a cluster or outbreak (A-III).
extremes of age, abscess in an area difficult to drain (eg, face,hand, and genitalia), associated septic phlebitis, and lack of Pediatric considerations response to incision and drainage alone (A-III).
For children with minor skin infections (such as impetigo) For outpatients with purulent cellulitis (eg, cellulitis and secondarily infected skin lesions (such as eczema, ulcers, or associated with purulent drainage or exudate in the absence of lacerations), mupirocin 2% topical ointment can be used (A-III).
a drainable abscess), empirical therapy for CA-MRSA is Tetracyclines should not be used in children ,8 years of recommended pending culture results. Empirical therapy for infection due to b-hemolytic streptococci is likely to be In hospitalized children with cSSTI, vancomycin is unnecessary (A-II). Five to 10 days of therapy is recom- recommended (A-II). If the patient is stable without ongoing mended but should be individualized on the basis of the bacteremia or intravascular infection, empirical therapy with patient's clinical response.
clindamycin 10–13 mg/kg/dose IV every 6–8 h (to administer For outpatients with nonpurulent cellulitis (eg, cellulitis 40 mg/kg/day) is an option if the clindamycin resistance rate is with no purulent drainage or exudate and no associated low (eg, 10%) with transition to oral therapy if the strain is abscess), empirical therapy for infection due to b-hemolytic susceptible (A-II). Linezolid 600 mg PO/IV twice daily for streptococci is recommended (A-II). The role of CA-MRSA is children >12 years of age and 10 mg/kg/dose PO/IV every 8 h unknown. Empirical coverage for CA-MRSA is recommended for children ,12 years of age is an alternative (A-II).
in patients who do not respond to b-lactam therapy and may beconsidered in those with systemic toxicity. Five to 10 days of II. What is the management of recurrent MRSA SSTIs? therapy is recommended but should be individualized on the basis of the patient's clinical response.
For empirical coverage of CA-MRSA in outpatients with Preventive educational messages on personal hygiene SSTI, oral antibiotic options include the following: clindamycin and appropriate wound care are recommended for all patients (A-II), trimethoprim-sulfamethoxazole (TMP-SMX) (A-II), with SSTI. Instructions should be provided to: 286 d CID 2011:52 (1 February) d Liu et al i. Keep draining wounds covered with clean, dry bandages ii. Contacts should be evaluated for evidence of S. aureus ii. Maintain good personal hygiene with regular bathing and a. Symptomatic contacts should be evaluated and treated (A- cleaning of hands with soap and water or an alcohol-based III); nasal and topical body decolonization strategies may be hand gel, particularly after touching infected skin or an item considered following treatment of active infection (C-III).
that has directly contacted a draining wound (A-III).
b. Nasal and topical body decolonization of asymptomatic iii. Avoid reusing or sharing personal items (eg, disposable household contacts may be considered (C-III).
razors, linens, and towels) that have contacted infected skin The role of cultures in the management of patients with recurrent SSTI is limited: Environmental hygiene measures should be considered i. Screening cultures prior to decolonization are not in patients with recurrent SSTI in the household or community routinely recommended if at least 1 of the prior infections was documented as due to MRSA (B-III).
i. Focus cleaning efforts on high-touch surfaces (ie, surfaces ii. Surveillance cultures following a decolonization regimen that come into frequent contact with people's bare skin each are not routinely recommended in the absence of an active day, such as counters, door knobs, bath tubs, and toilet seats) infection (B-III).
that may contact bare skin or uncovered infections (C-III).
ii. Commercially available cleaners or detergents appropriate III. What is the management of MRSA bacteremia and infective for the surface being cleaned should be used according to label instructions for routine cleaning of surfaces (C-III).
Bacteremia and Infective Endocarditis, Native Valve Decolonization may be considered in selected cases if: For adults with uncomplicated bacteremia (defined as patients with positive blood culture results and the following: i. A patient develops a recurrent SSTI despite optimizing exclusion of endocarditis; no implanted prostheses; follow-up wound care and hygiene measures (C-III).
blood cultures performed on specimens obtained 2–4 days ii. Ongoing transmission is occurring among household after the initial set that do not grow MRSA; defervescence members or other close contacts despite optimizing wound within 72 h of initiating effective therapy; and no evidence of care and hygiene measures (C-III).
metastatic sites of infection), vancomycin (A-II) or daptomycin Decolonization strategies should be offered in conjunction 6 mg/kg/dose IV once daily (AI) for at least 2 weeks. For with ongoing reinforcement of hygiene measures and may complicated bacteremia (defined as patients with positive blood include the following: culture results who do not meet criteria for uncomplicatedbacteremia), 4–6 weeks of therapy is recommended, depending i. Nasal decolonization with mupirocin twice daily for 5–10 on the extent of infection. Some experts recommend higher days (C-III).
dosages of daptomycin at 8–10 mg/kg/dose IV once daily (B-III).
ii. Nasal decolonization with mupirocin twice daily for 5–10 For adults with infective endocarditis, IV vancomycin days and topical body decolonization regimens with a skin (A-II) or daptomycin 6 mg/kg/dose IV once daily (A-I) for 6 antiseptic solution (eg, chlorhexidine) for 5–14 days or dilute weeks is recommended. Some experts recommend higher bleach baths. (For dilute bleach baths, 1 teaspoon per gallon dosages of daptomycin at 8–10 mg/kg/dose IV once daily of water [or ¼ cup per ¼ tub or 13 gallons of water] given for 15 min twice weekly for 3 months can be considered.) Addition of gentamicin to vancomycin is not recom- mended for bacteremia or native valve infective endocarditis(A-II).
Oral antimicrobial therapy is recommended for the Addition of rifampin to vancomycin is not recommen- treatment of active infection only and is not routinely re- ded for bacteremia or native valve infective endocarditis (A-I).
commended for decolonization (A-III). An oral agent in A clinical assessment to identify the source and extent of combination with rifampin, if the strain is susceptible, may be the infection with elimination and/or debridement of other considered for decolonization if infections recur despite above sites of infection should be conducted (A-II).
measures (CIII).
Additional blood cultures 2–4 days after initial positive In cases where household or interpersonal transmission cultures and as needed thereafter are recommended to document clearance of bacteremia (A-II).
i. Personal and environmental hygiene measures in the Echocardiography is recommended for all adult patient and contacts are recommended (A-III).
patients with bacteremia. Transesophageal echocardiography MRSA Treatment Guidelines d CID 2011:52 (1 February) d 287 (TEE) is preferred over transthoracic echocardiography (TTE) In patients with MRSA pneumonia complicated by empyema, antimicrobial therapy against MRSA should be used Evaluation for valve replacement surgery is recommen- in conjunction with drainage procedures (A-III).
ded if large vegetation (.10 mm in diameter), occurrence of Pediatric considerations >1 embolic event during the first 2 weeks of therapy, severevalvular insufficiency, valvular perforation or dehiscence, In children, IV vancomycin is recommended (A-II). If decompensated heart failure, perivalvular or myocardial the patient is stable without ongoing bacteremia or intravas- abscess, new heart block, or persistent fevers or bacteremia cular infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h are present (A-II).
(to administer 40 mg/kg/day) can be used as empirical therapyif the clindamycin resistance rate is low (eg, 10%) with Infective Endocarditis, Prosthetic Valve transition to oral therapy if the strain is susceptible (A-II).
IV vancomycin plus rifampin 300 mg PO/IV every 8 h Linezolid 600 mg PO/IV twice daily for children >12 years of for at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h age and 10 mg/kg/dose every 8 h for children ,12 years of age is for 2 weeks (B-III).
an alternative (A-II).
Early evaluation for valve replacement surgery is V. What is the management of MRSA bone and joint infections? recommended (A-II).
Pediatric considerations Surgical debridement and drainage of associated soft- tissue abscesses is the mainstay of therapy and should be In children, vancomycin 15 mg/kg/dose IV every 6 h is performed whenever feasible (A-II).
recommended for the treatment of bacteremia and infective The optimal route of administration of antibiotic endocarditis (A-II). Duration of therapy may range from 2 to therapy has not been established. Parenteral, oral, or initial 6 weeks depending on source, presence of endovascular parenteral therapy followed by oral therapy may be used infection, and metastatic foci of infection. Data regarding the depending on individual patient circumstances (A-III).
safety and efficacy of alternative agents in children are limited, Antibiotics available for parenteral administration in- although daptomycin 6–10 mg/kg/dose IV once daily may be clude IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV an option (C-III). Clindamycin or linezolid should not be once daily (B-II). Some antibiotic options with parenteral and used if there is concern for infective endocarditis or oral routes of administration include the following: TMP-SMX endovascular source of infection but may be considered in 4 mg/kg/dose (TMP component) twice daily in combination children whose bacteremia rapidly clears and is not related to with rifampin 600 mg once daily (B-II), linezolid 600 mg twice an endovascular focus (B-III).
daily (B-II), and clindamycin 600 mg every 8 h (B-III).
Data are insufficient to support the routine use of Some experts recommend the addition of rifampin combination therapy with rifampin or gentamicin in children 600 mg daily or 300–450 mg PO twice daily to the antibiotic with bacteremia or infective endocarditis (C-III); the decision chosen above (B-III). For patients with concurrent bacter- to use combination therapy should be individualized.
emia, rifampin should be added after clearance of bacteremia.
Echocardiogram is recommended in children with con- The optimal duration of therapy for MRSA osteomye- genital heart disease, bacteremia more than 2–3 days in duration, litis is unknown. A minimum 8-week course is recommended or other clinical findings suggestive of endocarditis (A-III).
(A-II). Some experts suggest an additional 1–3 months (andpossibly longer for chronic infection or if debridement is not IV. What is the management of MRSA pneumonia? performed) of oral rifampin-based combination therapy with TMP-SMX, doxycycline-minocycline, clindamycin, or a fluo- For hospitalized patients with severe community- roquinolone, chosen on the basis of susceptibilities (C-III).
acquired pneumonia defined by any one of the following: (1) Magnetic resonance imaging (MRI) with gadolinium is a requirement for intensive care unit (ICU) admission, (2) the imaging modality of choice, particularly for detection of necrotizing or cavitary infiltrates, or (3) empyema, empirical early osteomyelitis and associated soft-tissue disease (A-II).
therapy for MRSA is recommended pending sputum and/or Erythrocyte sedimentation rate (ESR) and/or C-reactive pro- blood culture results (A-III).
tein (CRP) level may be helpful to guide response to therapy For health care–associated MRSA (HA-MRSA) or CA- MRSA pneumonia, IV vancomycin (A-II) or linezolid 600 mg PO/IV twice daily (A-II) or clindamycin 600 mg PO/IV 3 timesdaily (B-III), if the strain is susceptible, is recommended for 7– Drainage or debridement of the joint space should 21 days, depending on the extent of infection.
always be performed (A-II).
288 d CID 2011:52 (1 February) d Liu et al For septic arthritis, refer to antibiotic choices for VI. What is the management of MRSA infections of the CNS? osteomyelitis (recommendation 37 above). A 3–4-week course of therapy is suggested (A-III).
IV vancomycin for 2 weeks is recommended (B-II).
Some experts recommend the addition of rifampin 600 mg Device-related osteoarticular infections daily or 300–450 mg twice daily (B-III).
For early-onset (,2 months after surgery) or acute Alternatives include the following: linezolid 600 mg PO/IV hematogenous prosthetic joint infections involving a stable twice daily (B-II) or TMP-SMX 5 mg/kg/dose IV every 8–12 h implant with short duration (<3 weeks) of symptoms and debridement (but device retention), initiate parenteral therapy For CNS shunt infection, shunt removal is recommen- (refer to antibiotic recommendations for osteomyelitis) plus ded, and it should not be replaced until cerebrospinal fluid rifampin 600 mg daily or 300–450 mg PO twice daily for 2 (CSF) cultures are repeatedly negative (A-II).
weeks followed by rifampin plus a fluoroquinolone, TMP-SMX, a tetracycline or clindamycin for 3 or 6 months for hips Brain abscess, subdural empyema, spinal epidural abscess and knees, respectively (A-II). Prompt debridement with device Neurosurgical evaluation for incision and drainage is removal whenever feasible is recommended for unstable recommended (A-II).
implants, late-onset infections, or in those with long duration IV vancomycin for 4–6 weeks is recommended (B-II).
(.3 weeks) of symptoms (A-II).
Some experts recommend the addition of rifampin 600 mg For early-onset spinal implant infections (<30 days after daily or 300–450 mg twice daily (B-III).
surgery) or implants in an actively infected site, initial Alternatives include the following: linezolid 600 mg PO/IV parenteral therapy plus rifampin followed by prolonged oral twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h therapy is recommended (B-II). The optimal duration of parenteral and oral therapy is unclear; the latter should be continued until spine fusion has occurred (B-II). For late-onset Septic Thrombosis of Cavernous or Dural Venous Sinus infections (.30 days after implant placement), device removal Surgical evaluation for incision and drainage of contig- whenever feasible is recommended (B-II).
uous sites of infection or abscess is recommended whenever Long-term oral suppressive antibiotics (eg, TMP-SMX, possible (A-II). The role of anticoagulation is controversial.
a tetracycline, a fluoroquinolone [which should be given in IV vancomycin for 4–6 weeks is recommended (B-II).
conjunction with rifampin due to the potential emergence of Some experts recommend the addition of rifampin 600 mg fluoroquinolone resistance, particularly if adequate surgical daily or 300–450 mg twice daily (B-III).
debridement is not possible should be given in conjunction Alternatives include the following: linezolid 600 mg PO/IV with rifampin], or clindamycin) with or without rifampin may twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h be considered in selected cases, particularly if device removal not possible (B-III).
Pediatric considerations Pediatric considerations IV vancomycin is recommended (A-II).
osteomyelitis and septic arthritis, IV vancomycin is recom- VII. What is the role of adjunctive therapies for the treatment ofMRSA infections? mended (A-II). If the patient is stable without ongoingbacteremia or intravascular infection, clindamycin 10–13 mg/ Protein synthesis inhibitors (eg, clindamycin and line- kg/dose IV every 6–8 h (to administer 40 mg/kg/day) can be zolid) and intravenous immunoglobulin (IVIG) are not used as empirical therapy if the clindamycin resistance rate is routinely recommended as adjunctive therapy for the manage- low (eg, 10%) with transition to oral therapy if the strain is ment of invasive MRSA disease (A-III). Some experts may susceptible (A-II). The exact duration of therapy should be consider these agents in selected scenarios (eg, necrotizing individualized, but typically a minimum 3–4-week course is pneumonia or severe sepsis) (C-III).
recommended for septic arthritis and a 4–6-week course isrecommended for osteomyelitis.
VIII. What are the recommendations for vancomycin dosing and Alternatives to vancomycin and clindamycin include the following: daptomycin 6 mg/kg/day IV once daily (C-III) or These recommendations are based on a consensus statement of linezolid 600 mg PO/IV twice daily for children >12 years of the American Society of Health-System Pharmacists, the IDSA, age and 10 mg/kg/dose every 8 h for children ,12 years of age and The Society of Infectious Diseases Pharmacists on guidelines for vancomycin dosing [3, 4].
MRSA Treatment Guidelines d CID 2011:52 (1 February) d 289 i. If the patient has had a clinical and microbiologic response IV vancomycin 15–20 mg/kg/dose (actual body weight) to vancomycin, then it may be continued with close follow-up every 8–12 h, not to exceed 2 g per dose, is recommended in ii. If the patient has not had a clinical or microbiologic patients with normal renal function (B-III).
response to vancomycin despite adequate debridement and In seriously ill patients (eg, those with sepsis, meningitis, removal of other foci of infection, an alternative to vancomycin pneumonia, or infective endocarditis) with suspected MRSA is recommended regardless of MIC.
infection, a loading dose of 25–30 mg/kg (actual body weight) For isolates with a vancomycin MIC .2 lg/mL (eg, may be considered. (Given the risk of red man syndrome and vancomycin-intermediate S. aureus [VISA] or vancomycin- possible anaphylaxis associated with large doses of vancomycin, resistant S. aureus [VRSA]), an alternative to vancomycin one should consider prolonging the infusion time to 2 h and should be used (A-III).
use of an antihistamine prior to administration of the loading X. What is the management of persistent MRSA bacteremia and dose.) (C-III).
vancomycin treatment failures in adult patients? Trough vancomycin concentrations are the most accurate and practical method to guide vancomycin dosing A search for and removal of other foci of infection, (B-II). Serum trough concentrations should be obtained at drainage or surgical debridement is recommended (A-III).
steady state conditions, prior to the fourth or fifth dose.
High-dose daptomycin (10 mg/kg/day), if the isolate is Monitoring of peak vancomycin concentrations is not susceptible, in combination with another agent (e.g. gentamicin recommended (B-II).
1 mg/kg IV every 8 h, rifampin 600 mg PO/IV daily or For serious infections, such as bacteremia, infective 300-450 mg PO/IV twice daily, linezolid 600 mg PO/IV BID, endocarditis, osteomyelitis, meningitis, pneumonia, and severe TMP-SMX 5 mg/kg IV twice daily, or a beta-lactam antibiotic) SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin should be considered (B-III).
trough concentrations of 15–20 lg/mL are recommended If reduced susceptibility to vancomycin and daptomycin are present, options may include the following: quinupristin- For most patients with SSTI who have normal renal dalfopristin 7.5 mg/kg/dose IV every 8 h, TMP-SMX 5 mg/kg/ function and are not obese, traditional doses of 1 g every 12 h dose IV twice daily, linezolid 600 mg PO/IV twice daily, or are adequate, and trough monitoring is not required (B-II).
telavancin 10 mg/kg/dose IV once daily (C-III). These options Trough vancomycin monitoring is recommended for may be given as a single agent or in combination with other serious infections and patients who are morbidly obese, have renal dysfunction (including those receiving dialysis), or havefluctuating volumes of distribution (A-II).
XI. What is the management of MRSA infections in neonates? Continuous infusion vancomycin regimens are not Neonatal pustulosis recommended (A-II).
For mild cases with localized disease, topical treatment with mupirocin may be adequate in full-term neonates andyoung infants (A-III).
Data are limited to guide vancomycin dosing in For localized disease in a premature or very low- children. IV vancomycin 15 mg/kg/dose every 6 h is birthweight infant or more-extensive disease involving multiple recommended in children with serious or invasive disease sites in full-term infants, IV vancomycin or clindamycin is recommended, at least initially, until bacteremia is excluded The efficacy and safety of targeting trough concentrations of 15–20 lg/mL in children requires additional study but shouldbe considered in those with serious infections, such as Neonatal MRSA sepsis bacteremia, infective endocarditis, osteomyelitis, meningitis, IV vancomycin is recommended, dosing as outlined in pneumonia, and severe SSTI (ie, necrotizing fasciitis) (B-III).
the Red Book (A-II) [160].
Clindamycin and linezolid are alternatives for non- IX. How should results of vancomycin susceptibility testing be endovascular infections (B-II).
used to guide therapy? The prevalence of MRSA has steadily increased since the first For isolates with a vancomycin minimum inhibitory clinical isolate was described in 1961, with an estimated 94,360 concentration (MIC) <2 lg/mL (eg, susceptible according to cases of invasive MRSA disease in the United States in 2005 [5].
Clinical and Laboratory Standards Institute [CLSI] breakpoints), Initially almost exclusively health care–associated, by the mid- the patient's clinical response should determine the continued 1990s, MRSA strains were reported as causing infections among use of vancomycin, independent of the MIC (A-III).
previously healthy individuals in the community who lacked 290 d CID 2011:52 (1 February) d Liu et al health care–associated risk factors [6]. Unlike HA-MRSA, these so-called CA-MRSA isolates are susceptible to many non–ß- The Expert Panel wishes to express its gratitude to Drs. Gordon Archer, lactam antibiotics. Furthermore, they are genetically distinct Frank Lowy, and Brad Spellberg for their thoughtful reviews of earlier drafts from HA-MRSA isolates and contain a novel cassette element, of the guideline. The Expert Panel also recognizes the following for theirimportant contributions in identifying critical gaps where funding of re- SCCmec IV and exotoxin, Panton-Valentine leukocidin (PVL).
search is needed to advance clinical treatment and care: William Burman, The epidemiology of MRSA has become increasingly complex as David M. Margolis, and Louis B. Rice (IDSA Research Committee), Stanley CA-MRSA and HA-MRSA strains have co-mingled both in the C. Deresinski (IDSA SPGC), and Padma Natarajan (IDSA staff). Thefindings and conclusions of this report are those of the authors and do not community and in health care facilities [7, 8]. Not unexpectedly, necessarily represent the official position of the Centers for Disease Control MRSA disease has had an enormous clinical and economic and Prevention.
impact [9, 10].
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment The wide spectrum of illness caused by MRSA includes SSTIs, with respect to particular patients or special clinical situations. The IDSA con- bacteremia and endocarditis, pneumonia, bone and joint in- siders adherence to these guidelines to be voluntary, with the ultimate de- fections, CNS disease, and toxic shock and sepsis syndromes.
termination regarding their application to be made by the physician in the light ofeach patient's individual circumstances.
CA-MRSA was the most common cause of SSTI in a geo- Financial support.
graphically diverse network of emergency departments in the Potential conflicts of interest.
H.F.C. has received honoraria and re- United States [11]; however, there may be differences in local search grants and has served as a consultant to Cubist, Ortho-McNeil,Pfizer, Theravance, and Targanta. S. E. C. has received honoraria from epidemiology to consider when implementing these guidelines.
Forest and RibX, has served as a consultant for Merck and has received SSTIs may range in clinical presentation from a simple abscess research support from Astellas, Cubist and AdvanDx. R.D. has received or cellulitis to deeper soft-tissue infections, such as pyomyositis, research funding from Pfizer, Clorox, Sanofi Pasteur, Sage, and GeneOhm.
S.L.K. has received grant funding from Pfizer, has served as MRSA Lead- necrotizing fasciitis, and mediastinitis as a complication of ret- ership Advisor to Pfizer, and is participating in a pediatric daptomycin ropharyngeal abscess [12–15]. Bacteremia accompanies the study. A.W.K. has received honoraria and grants from Cubist Pharma- majority (75%) of cases of invasive MRSA disease [5]. A mul- ceuticals, Merck, Wyeth, and Pfizer and has served as a consultant forCubist Pharmaceuticals, Theravance, Astellas, Pfizer, Merck, and Ortho- titude of disease manifestations have been described, including, McNeil and has owned stock from Cubist Pharmaceutical, Pfizer, and but not limited to, infective endocarditis; myocardial, peri- Johnson and Johnson. D.P.L. has received research support from Cubist,Johnson & Johnson, and Theravance and has served as a speaker for Cubist.
nephric, hepatic, and splenic abscesses; septic thrombophlebitis B.E.M. has served as a consultant and received research support from with and without pulmonary emboli [16]; necrotizing pneu- Johnson & Johnson, Astellas, Pfizer, Cubist, Theravance, Targanta, Sanofi- monia [17–21]; osteomyelitis complicated by subperiosteal ab- Aventis, Vicuron Pharmaceuticals, and Wyeth-Ayerst. M.R. has receivedgrants and or has served as a consultant speaker for the Pfizer, Cubist, scesses; venous thrombosis and sustained bacteremia [16, 22, Theravance/Astellas, Targanta, and Johnson & Johnson. D.A.T. has served 23]; severe ocular infections, including endophthalmitis [24]; on the advisory board to Pfizer, Ortho-McNeil, Astellas, Schering-Plough, sepsis with purpura fulminans [25]; and Waterhouse-Frider- and Replidyne. All other authors: no conflicts.
ichsen syndrome [26].
The Expert Panel addressed the following clinical questions in the 2010 Guidelines: 1. Calfee DP, Salgado CD, Classen D, et al. Strategies to prevent trans- mission of methicillin-resistant Staphylococcus aureus in acute care I. What is the management of SSTIs in the CA-MRSA era? hospitals. Infect Control Hosp Epidemiol 2008; 29(Suppl 1):S62–S80.
2. Anderson DJ, Kaye KS, Classen D, et al. Strategies to prevent surgical II. What is the management of recurrent MRSA SSTIs? site infections in acute care hospitals. Infect Control Hosp Epidemiol III. What is the management of MRSA bacteremia and 2008; 29(Suppl 1):S51–S61.
infective endocarditis? 3. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of IV. What is the management of MRSA pneumonia? vancomycin in adult patients: a consensus review of the AmericanSociety of Health-System Pharmacists, the Infectious Diseases Society V. What is the management of MRSA bone and joint of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009; 66:82–98.
VI. What is the management of MRSA infections of the CNS? 4. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin thera- peutic guidelines: a summary of consensus recommendations from the VII. What is the role of adjunctive therapies for the treatment Infectious Diseases Society of America, the American Society of of MRSA infections? Health-System Pharmacists, and the Society of Infectious Diseases VIII. What are the recommendations for vancomycin dosing Pharmacists. Clin Infect Dis 2009; 49:325–7.
5. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007; IX. How should results of vancomycin susceptibility testing be used to guide therapy? 6. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired X. What is the management of persistent MRSA bacteremia methicillin-resistant Staphylococcus aureus in children with no identi-fied predisposing risk. JAMA 1998; 279:593–8.
and vancomycin treatment failures? 7. Liu C, Graber CJ, Karr M, et al. A population-based study of XI. What is the management of MRSA in neonates? the incidence and molecular epidemiology of methicillin-resistant MRSA Treatment Guidelines d CID 2011:52 (1 February) d 291 Staphylococcus aureus disease in San Francisco, 2004–2005. Clin Infect 17. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset Dis 2008; 46:1637–46.
pneumonia in healthy adults caused by methicillin-resistant Staphylo- 8. D'Agata EM, Webb GF, Horn MA, et al. Modeling the invasion of coccus aureus carrying the Panton-Valentine leukocidin genes. Clin community-acquired methicillin-resistant Staphylococcus aureus into Infect Dis 2005; 40:100–7.
hospitals. Clin Infect Dis 2009; 48:274–84.
18. Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired 9. Purcell K, Fergie J, Peterson MD. Economic impact of the community- pneumonia due to Staphylococcus aureus, 2003-04 influenza season.
acquired methicillin-resistant Staphylococcus aureus epidemic on Emerg Infect Dis 2006; 12:894–9.
the Driscoll Children's Health Plan. Pediatr Infect Dis J 2006; 25: 19. Centers for Disease Control and Prevention. Severe methicillin-re- sistant Staphylococcus aureus community-acquired pneumonia associ- 10. Noskin GA, Rubin RJ, Schentag JJ, et al. The burden of Staphylococcus ated with influenza–Louisiana Georgia, December 2006-January 2007.
aureus infections on hospitals in the United States: an analysis of the MMWR Morb Mortal Wkly Rep 2007; 56:325–9.
2000 and 2001 Nationwide Inpatient Sample Database. Arch Intern 20. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonary manifestations Med 2005; 165:1756–61.
in children with invasive community-acquired Staphylococcus aureus 11. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S.
infection. Clin Infect Dis 2005; 41:583–90.
aureus infections among patients in the emergency department. N Engl 21. Finelli L, Fiore A, Dhara R, et al. Influenza-associated pediatric mor- J Med 2006; 355:666–74.
tality in the United States: increase of Staphylococcus aureus co- 12. Lee TC, Carrick MM, Scott BG, et al. Incidence and clinical charac- infection. Pediatrics 2008; 122:805–11.
teristics of methicillin-resistant Staphylococcus aureus necrotizing fas- 22. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute ciitis in a large urban hospital. Am J Surg 2007; 194:809–12; discussion, hematogenous osteomyelitis and septic arthritis: emergence of com- munity-associated methicillin-resistant Staphylococcus aureus. J Pediatr 13. Pannaraj PS, Hulten KG, Gonzalez BE, et al. Infective pyomyositis and Orthop 2006; 26:703–8.
myositis in children in the era of community-acquired, methicillin- 23. Crary SE, Buchanan GR, Drake CE, et al. Venous thrombosis and resistant Staphylococcus aureus infection. Clin Infect Dis 2006; 43:953–60.
thromboembolism in children with osteomyelitis. J Pediatr 2006; 14. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus 24. Rutar T, Chambers HF, Crawford JB, et al. Ophthalmic manifestations aureus in Los Angeles. N Engl J Med 2005; 352:1445–53.
of infections caused by the USA300 clone of community-associated 15. Wright CT, Stocks RM, Armstrong DL, et al. Pediatric mediastinitis as methicillin-resistant Staphylococcus aureus. Ophthalmology 2006; a complication of methicillin-resistant Staphylococcus aureus retro- pharyngeal abscess. Arch Otolaryngol Head Neck Surg 2008; 25. Kravitz GR, Dries DJ, Peterson ML, et al. Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis 2005; 40:941–7.
16. Gonzalez BE, Teruya J, Mahoney DH Jr., et al. Venous thrombosis 26. Adem PV, Montgomery CP, Husain AN, et al. Staphylococcus aureus associated with staphylococcal osteomyelitis in children. Pediatrics sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J 2006; 117:1673–9.
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292 d CID 2011:52 (1 February) d Liu et al


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