Manejo de Estafilococo Meticilinoresistente

IDSA GUIDELINES
Clinical Practice Guidelines by the Infectious Diseases

Society of America for the Treatment of Methicillin-
Resistant Staphylococcus aureus Infections in Adults
and Children
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Catherine Liu,1 Arnold Bayer,3,5 Sara E. Cosgrove,6 Robert S. Daum,7 Scott K. Fridkin,8 Rachel J. Gorwitz,9
Sheldon L. Kaplan,10 Adolf W. Karchmer,11 Donald P. Levine,12 Barbara E. Murray,14 Michael J. Rybak,12,13 David
A. 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 Emergency
Medicine and Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA; 5Department of Medicine, David Geffen School of Medicine at University
of California Los Angeles; 6Division of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland; 7Department of Pediatrics, Section
of 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 of
Medicine, 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). The
guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA
infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA
disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and
joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding
vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility
to vancomycin, and vancomycin treatment failures.
EXECUTIVE SUMMARY encountered by adult and pediatric clinicians who care for
patients with MRSA infections. The guidelines address
MRSA is a significant cause of both health care–associated issues related to the use of vancomycin therapy in the
and community-associated infections. This document treatment of MRSA infections, including dosing and
constitutes the first guidelines of the IDSA on the treat- monitoring, current limitations of susceptibility testing,
ment of MRSA infections. The primary objective of these and the use of alternate therapies for those patients with
guidelines is to provide recommendations on the man- vancomycin treatment failure and infection due to strains
agement of some of the most common clinical syndromes with reduced susceptibility to vancomycin. The guidelines
do not discuss active surveillance testing or other
Received 28 October 2010; accepted 17 November 2010. MRSA infection–prevention strategies in health care set-
Correspondence: Catherine Liu, MD, Dept of Medicine, Div of Infectious
Diseases, University of California–San Francisco, San Francisco, California, 94102
tings, which are addressed in previously published
(catherine.liu@ucsf.edu). guidelines [1, 2]. Each section of the guidelines begins
Clinical Infectious Diseases 2011;52(3):e18–e55 with a specific clinical question and is followed by
Ó The Author 2011. Published by Oxford University Press on behalf of the
Infectious Diseases Society of America. All rights reserved. For Permissions,
numbered recommendations and a summary of the
please e-mail:journals.permissions@oup.com. most-relevant evidence in support of the recom-
1058-4838/2011/523-0001$37.00
mendations. Areas of controversy in which data are
DOI: 10.1093/cid/ciq146
e18 d CID 2011:52 (1 February) d Liu et al

limited or conflicting and where additional research is needed are combination with a b-lactam (eg, amoxicillin) (A-II) or linezolid
indicated throughout the document and are highlighted in the alone (A-II).
Research Gaps section. The key recommendations are summa- 6. The use of rifampin as a single agent or as adjunctive
rized below in the Executive Summary; each topic is discussed in therapy for the treatment of SSTI is not recommended (A-III).
greater detail within the main body of the guidelines. 7. For hospitalized patients with complicated SSTI (cSSTI;
Please note that specific recommendations on vancomycin defined as patients with deeper soft-tissue infections, surgical/
dosing and monitoring are not discussed in the sections for each traumatic wound infection, major abscesses, cellulitis, and
clinical syndrome but are collectively addressed in detail in infected ulcers and burns), in addition to surgical debridement
Section VIII. and broad-spectrum antibiotics, empirical therapy for
MRSA should be considered pending culture data. Options
I. What is the management of skin and soft-tissue infections include the following: intravenous (IV) vancomycin (A-I), oral
(SSTIs) in the era of community-associated MRSA (CA-MRSA)? (PO) or IV linezolid 600 mg twice daily (A-I), daptomycin
SSTIs 4 mg/kg/dose IV once daily (A-I), telavancin 10 mg/kg/dose IV

once daily (A-I), and clindamycin 600 mg IV or PO 3 times
1. For a cutaneous abscess, incision and drainage is the
a day (A-III). A b-lactam antibiotic (eg, cefazolin) may be
primary treatment (A-II). For simple abscesses or boils,
considered in hospitalized patients with nonpurulent cellulitis
incision and drainage alone is likely to be adequate, but
with modification to MRSA-active therapy if there is no clinical
additional data are needed to further define the role of
response (A-II). Seven to 14 days of therapy is recommended
antibiotics, if any, in this setting.
but should be individualized on the basis of the patient’s
2. Antibiotic therapy is recommended for abscesses
clinical response.
associated with the following conditions: severe or extensive
8. Cultures from abscesses and other purulent SSTIs are
disease (eg, involving multiple sites of infection) or rapid
recommended in patients treated with antibiotic therapy,
progression in presence of associated cellulitis, signs and
patients with severe local infection or signs of systemic illness,
symptoms of systemic illness, associated comorbidities or
patients who have not responded adequately to initial treatment,
immunosuppression, extremes of age, abscess in an area
and if there is concern for a cluster or outbreak (A-III).
difficult to drain (eg, face, hand, and genitalia), associated
septic phlebitis, and lack of response to incision and drainage Pediatric considerations
alone (A-III). 9. For children with minor skin infections (such as impetigo)
3. 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 10. Tetracyclines should not be used in children ,8 years of
recommended pending culture results. Empirical therapy for age (A-II).
infection due to b-hemolytic streptococci is likely to be 11. 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
4. 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 be
considered 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 Recurrent SSTIs
basis of the patient’s clinical response.
12. Preventive educational messages on personal hygiene
5. For empirical coverage of CA-MRSA in outpatients with
and appropriate wound care are recommended for all patients
SSTI, oral antibiotic options include the following: clindamycin
with SSTI. Instructions should be provided to:
(A-II), trimethoprim-sulfamethoxazole (TMP-SMX) (A-II),
a tetracycline (doxycycline or minocycline) (A-II), and linezolid i. Keep draining wounds covered with clean, dry bandages
(A-II). If coverage for both b-hemolytic streptococci and (A-III).
CA-MRSA is desired, options include the following: ii. Maintain good personal hygiene with regular bathing and
clindamycin alone (A-II) or TMP-SMX or a tetracycline in cleaning of hands with soap and water or an alcohol-based
MRSA Treatment Guidelines d CID 2011:52 (1 February) d e19

hand gel, particularly after touching infected skin or an item b. Nasal and topical body decolonization of asymptomatic
that has directly contacted a draining wound (A-III). household contacts may be considered (C-III).
iii. Avoid reusing or sharing personal items (eg, disposable
18. The role of cultures in the management of patients with
razors, linens, and towels) that have contacted infected skin
recurrent SSTI is limited:
(A-III).
i. Screening cultures prior to decolonization are not
13. Environmental hygiene measures should be considered
routinely recommended if at least 1 of the prior infections
in patients with recurrent SSTI in the household or community
was documented as due to MRSA (B-III).
setting:
ii. Surveillance cultures following a decolonization regimen
i. Focus cleaning efforts on high-touch surfaces (ie, surfaces are not routinely recommended in the absence of an active
that come into frequent contact with people’s bare skin each infection (B-III).
day, such as counters, door knobs, bath tubs, and toilet seats)
III. What is the management of MRSA bacteremia and infective
that may contact bare skin or uncovered infections (C-III).
endocarditis?

ii. Commercially available cleaners or detergents appropriate
Bacteremia and Infective Endocarditis, Native Valve
for the surface being cleaned should be used according to label
instructions for routine cleaning of surfaces (C-III). 19. For adults with uncomplicated bacteremia (defined as
patients with positive blood culture results and the following:
14. Decolonization may be considered in selected cases if: exclusion of endocarditis; no implanted prostheses; follow-up
i. A patient develops a recurrent SSTI despite optimizing blood cultures performed on specimens obtained 2–4 days
wound care and hygiene measures (C-III). after the initial set that do not grow MRSA; defervescence
ii. Ongoing transmission is occurring among household within 72 h of initiating effective therapy; and no evidence of
members or other close contacts despite optimizing wound metastatic sites of infection), vancomycin (A-II) or daptomycin
care and hygiene measures (C-III). 6 mg/kg/dose IV once daily (AI) for at least 2 weeks. For
complicated bacteremia (defined as patients with positive blood
15. Decolonization strategies should be offered in conjunction
culture results who do not meet criteria for uncomplicated
with ongoing reinforcement of hygiene measures and may
bacteremia), 4–6 weeks of therapy is recommended, depending
include the following:
on the extent of infection. Some experts recommend higher
i. Nasal decolonization with mupirocin twice daily for 5–10 dosages of daptomycin at 8–10 mg/kg/dose IV once daily (B-III).
days (C-III). 20. For adults with infective endocarditis, IV vancomycin
ii. Nasal decolonization with mupirocin twice daily for 5–10 (A-II) or daptomycin 6 mg/kg/dose IV once daily (A-I) for 6
days and topical body decolonization regimens with a skin weeks is recommended. Some experts recommend higher
antiseptic solution (eg, chlorhexidine) for 5–14 days or dilute dosages of daptomycin at 8–10 mg/kg/dose IV once daily
bleach baths. (For dilute bleach baths, 1 teaspoon per gallon (B-III).
of water [or ¼ cup per ¼ tub or 13 gallons of water] given 21. Addition of gentamicin to vancomycin is not recom-
for 15 min twice weekly for 3 months can be considered.) mended for bacteremia or native valve infective endocarditis
(C-III). (A-II).
22. Addition of rifampin to vancomycin is not recommen-
16. Oral antimicrobial therapy is recommended for the
ded for bacteremia or native valve infective endocarditis (A-I).
treatment of active infection only and is not routinely re-
23. A clinical assessment to identify the source and extent of
commended for decolonization (A-III). An oral agent in
the infection with elimination and/or debridement of other
combination with rifampin, if the strain is susceptible, may be
sites of infection should be conducted (A-II).
considered for decolonization if infections recur despite above
24. Additional blood cultures 2–4 days after initial positive
measures (CIII).
cultures and as needed thereafter are recommended to
17. In cases where household or interpersonal transmission
document clearance of bacteremia (A-II).
is suspected:
25. Echocardiography is recommended for all adult
i. Personal and environmental hygiene measures in the patients with bacteremia. Transesophageal echocardiography
patient and contacts are recommended (A-III). (TEE) is preferred over transthoracic echocardiography (TTE)
ii. Contacts should be evaluated for evidence of S. aureus (A-II).
infection: 26. Evaluation for valve replacement surgery is recommen-
a. Symptomatic contacts should be evaluated and treated (A- ded if large vegetation (.10 mm in diameter), occurrence of
III); nasal and topical body decolonization strategies may be >1 embolic event during the first 2 weeks of therapy, severe
considered following treatment of active infection (C-III). valvular insufficiency, valvular perforation or dehiscence,

decompensated heart failure, perivalvular or myocardial (to administer 40 mg/kg/day) can be used as empirical therapy
abscess, new heart block, or persistent fevers or bacteremia if the clindamycin resistance rate is low (eg, ,10%) with
are present (A-II). transition to oral therapy if the strain is susceptible (A-II).
Linezolid 600 mg PO/IV twice daily for children >12 years of
Infective Endocarditis, Prosthetic Valve
age and 10 mg/kg/dose every 8 h for children ,12 years of age is
27. IV vancomycin plus rifampin 300 mg PO/IV every 8 h an alternative (A-II).
for at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h
V. What is the management of MRSA bone and joint infections?
for 2 weeks (B-III).
Osteomyelitis
28. Early evaluation for valve replacement surgery is
recommended (A-II). 36. Surgical debridement and drainage of associated soft-
tissue abscesses is the mainstay of therapy and should be
Pediatric considerations
performed whenever feasible (A-II).
29. In children, vancomycin 15 mg/kg/dose IV every 6 h is 37. The optimal route of administration of antibiotic

recommended for the treatment of bacteremia and infective therapy has not been established. Parenteral, oral, or initial
endocarditis (A-II). Duration of therapy may range from 2 to 6 parenteral therapy followed by oral therapy may be used
weeks depending on source, presence of endovascular infection, depending on individual patient circumstances (A-III).
and metastatic foci of infection. Data regarding the safety and 38. Antibiotics available for parenteral administration in-
efficacy of alternative agents in children are limited, although clude IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV
daptomycin 6–10 mg/kg/dose IV once daily may be an option once daily (B-II). Some antibiotic options with parenteral and
(C-III). Clindamycin or linezolid should not be used if there is oral routes of administration include the following: TMP-SMX
concern for infective endocarditis or endovascular source of 4 mg/kg/dose (TMP component) twice daily in combination
infection but may be considered in children whose bacteremia with rifampin 600 mg once daily (B-II), linezolid 600 mg twice
rapidly clears and is not related to an endovascular focus (B-III). daily (B-II), and clindamycin 600 mg every 8 h (B-III).
30. Data are insufficient to support the routine use of 39. 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.
31. Echocardiogram is recommended in children with con- 40. 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 (and
IV. What is the management of MRSA pneumonia? possibly longer for chronic infection or if debridement is not
Pneumonia performed) of oral rifampin-based combination therapy with
TMP-SMX, doxycycline-minocycline, clindamycin, or a fluo-
32. 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) 41. 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
33. For health care–associated MRSA (HA-MRSA) or CA- (B-III).
MRSA pneumonia, IV vancomycin (A-II) or linezolid 600 mg
PO/IV twice daily (A-II) or clindamycin 600 mg PO/IV 3 times Septic Arthritis
daily (B-III), if the strain is susceptible, is recommended for 7– 42. Drainage or debridement of the joint space should
21 days, depending on the extent of infection. always be performed (A-II).
34. In patients with MRSA pneumonia complicated by 43. For septic arthritis, refer to antibiotic choices for
empyema, antimicrobial therapy against MRSA should be used osteomyelitis (recommendation 37 above). A 3–4-week course
in conjunction with drainage procedures (A-III). of therapy is suggested (A-III).
Pediatric considerations Device-related osteoarticular infections
35. In children, IV vancomycin is recommended (A-II). If 44. For early-onset (,2 months after surgery) or acute
the patient is stable without ongoing bacteremia or intravas- hematogenous prosthetic joint infections involving a stable
cular infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h implant with short duration (<3 weeks) of symptoms and

debridement (but device retention), initiate parenteral therapy 51. 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-
Brain abscess, subdural empyema, spinal epidural abscess
SMX, a tetracycline or clindamycin for 3 or 6 months for hips
and knees, respectively (A-II). Prompt debridement with device 52. 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 53. 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
45. 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 54. 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 (C-III).

parenteral and oral therapy is unclear; the latter should be Septic Thrombosis of Cavernous or Dural Venous Sinus
continued until spine fusion has occurred (B-II). For late-onset
infections (.30 days after implant placement), device removal 55. Surgical evaluation for incision and drainage of contig-
whenever feasible is recommended (B-II). uous sites of infection or abscess is recommended whenever
46. 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 56. 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 57. 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 (C-III).
not possible (B-III).
58. IV vancomycin is recommended (A-II).
47. For children with acute hematogenous MRSA osteomye-
VII. What is the role of adjunctive therapies for the treatment of
litis and septic arthritis, IV vancomycin is recommended (A-II). If MRSA infections?
the patient is stable without ongoing bacteremia or intravascular
infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h (to 59. Protein synthesis inhibitors (eg, clindamycin and line-
administer 40 mg/kg/day) can be used as empirical therapy if the zolid) and intravenous immunoglobulin (IVIG) are not
clindamycin resistance rate is low (eg, ,10%) with transition to routinely recommended as adjunctive therapy for the manage-
oral therapy if the strain is susceptible (A-II). The exact ment of invasive MRSA disease (A-III). Some experts may
duration of therapy should be individualized, but typically consider these agents in selected scenarios (eg, necrotizing
a minimum 3–4-week course is recommended for septic arthritis pneumonia or severe sepsis) (C-III).
and a 4–6-week course is recommended for osteomyelitis.
VIII. What are the recommendations for vancomycin dosing and
48. Alternatives to vancomycin and clindamycin include the
monitoring?
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
(C-III).
for vancomycin dosing [3, 4].
VI. What is the management of MRSA infections of the CNS? Adults
Meningitis
60. IV vancomycin 15–20 mg/kg/dose (actual body weight)
49. IV vancomycin for 2 weeks is recommended (B-II). every 8–12 h, not to exceed 2 g per dose, is recommended in
Some experts recommend the addition of rifampin 600 mg patients with normal renal function (B-III).
daily or 300–450 mg twice daily (B-III). 61. In seriously ill patients (eg, those with sepsis, meningitis,
50. Alternatives include the following: linezolid 600 mg PO/IV pneumonia, or infective endocarditis) with suspected MRSA
twice daily (B-II) or TMP-SMX 5 mg/kg/dose IV every 8–12 h infection, a loading dose of 25–30 mg/kg (actual body weight)
(C-III). may be considered. (Given the risk of red man syndrome and

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?
62. Trough vancomycin concentrations are the most
71. A search for and removal of other foci of infection,
accurate and practical method to guide vancomycin dosing
drainage or surgical debridement is recommended (A-III).
(B-II). Serum trough concentrations should be obtained at
72. High-dose daptomycin (10 mg/kg/day), if the isolate is
steady state conditions, prior to the fourth or fifth dose.
susceptible, in combination with another agent (e.g. gentamicin
Monitoring of peak vancomycin concentrations is not
1 mg/kg IV every 8 h, rifampin 600 mg PO/IV daily or
recommended (B-II).
300-450 mg PO/IV twice daily, linezolid 600 mg PO/IV BID,
63. For serious infections, such as bacteremia, infective
TMP-SMX 5 mg/kg IV twice daily, or a beta-lactam antibiotic)
endocarditis, osteomyelitis, meningitis, pneumonia, and severe
should be considered (B-III).
SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin

73. If reduced susceptibility to vancomycin and daptomycin
trough concentrations of 15–20 lg/mL are recommended
are present, options may include the following: quinupristin-
(B-II).
dalfopristin 7.5 mg/kg/dose IV every 8 h, TMP-SMX 5 mg/kg/
64. For most patients with SSTI who have normal renal
dose IV twice daily, linezolid 600 mg PO/IV twice daily, or
function and are not obese, traditional doses of 1 g every 12 h
telavancin 10 mg/kg/dose IV once daily (C-III). These options
are adequate, and trough monitoring is not required (B-II).
may be given as a single agent or in combination with other
65. Trough vancomycin monitoring is recommended for
antibiotics.
serious infections and patients who are morbidly obese, have
renal dysfunction (including those receiving dialysis), or have XI. What is the management of MRSA infections in neonates?
fluctuating volumes of distribution (A-II). Neonatal pustulosis
66. Continuous infusion vancomycin regimens are not
74. For mild cases with localized disease, topical treatment
recommended (A-II).
with mupirocin may be adequate in full-term neonates and
Pediatrics young infants (A-III).
67. Data are limited to guide vancomycin dosing in 75. 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
(B-III). recommended, at least initially, until bacteremia is excluded
68. The efficacy and safety of targeting trough concentrations (A-II).
of 15–20 lg/mL in children requires additional study but should Neonatal MRSA sepsis
be considered in those with serious infections, such as 76. IV vancomycin is recommended, dosing as outlined in
bacteremia, infective endocarditis, osteomyelitis, meningitis, the Red Book (A-II) [160].
pneumonia, and severe SSTI (ie, necrotizing fasciitis) (B-III). 77. 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
69. For isolates with a vancomycin minimum inhibitory clinical isolate was described in 1961, with an estimated
concentration (MIC) <2 lg/mL (eg, susceptible according to 94,360 cases of invasive MRSA disease in the United States in
Clinical and Laboratory Standards Institute [CLSI] breakpoints), 2005 [5]. Initially almost exclusively health care–associated,
the patient’s clinical response should determine the continued by the mid-1990s, MRSA strains were reported as causing
use of vancomycin, independent of the MIC (A-III). infections among previously healthy individuals in the com-
munity who lacked health care–associated risk factors [6].
i. If the patient has had a clinical and microbiologic response Unlike HA-MRSA, these so-called CA-MRSA isolates are
to vancomycin, then it may be continued with close follow-up susceptible to many non–ß-lactam antibiotics. Furthermore,
ii. If the patient has not had a clinical or microbiologic they are genetically distinct from HA-MRSA isolates and
response to vancomycin despite adequate debridement and contain a novel cassette element, SCCmec IV and exotoxin,
removal of other foci of infection, an alternative to vancomycin Panton-Valentine leukocidin (PVL). The epidemiology of
is recommended regardless of MIC.
MRSA has become increasingly complex as CA-MRSA and
70. For isolates with a vancomycin MIC .2 lg/mL (eg, HA-MRSA strains have co-mingled both in the community
vancomycin-intermediate S. aureus [VISA] or vancomycin- and in health care facilities [7, 8]. Not unexpectedly, MRSA

disease has had an enormous clinical and economic impact METHODOLOGY
[9, 10].
The wide spectrum of illness caused by MRSA includes SSTIs, Panel Composition
bacteremia and endocarditis, pneumonia, bone and joint in- The IDSA Standards and Practice Guidelines Committee
fections, CNS disease, and toxic shock and sepsis syndromes. (SPGC) convened adult and pediatric infectious diseases experts
CA-MRSA was the most common cause of SSTI in a geo- in the management of patients with MRSA.
graphically diverse network of emergency departments in the
Literature Review and Analysis
United States [11]; however, there may be differences in local
For the 2010 guidelines, the Expert Panel completed the review
epidemiology to consider when implementing these guidelines.
and analysis of data published since 1961. Computerized liter-
SSTIs may range in clinical presentation from a simple abscess
ature searches of PUBMED of the English-language literature
or cellulitis to deeper soft-tissue infections, such as pyomyositis,
were performed from 1961 through 2010 using the terms
necrotizing fasciitis, and mediastinitis as a complication of ret-
‘‘methicillin-resistant Staphylococcus aureus’’ or ‘‘MRSA’’ and
ropharyngeal abscess [12–15]. Bacteremia accompanies the

focused on human studies but also included studies from ex-
majority (75%) of cases of invasive MRSA disease [5]. A mul-
perimental animal models and in vitro data. A few abstracts
titude of disease manifestations have been described, including,
from national meetings were included. There were few ran-
but not limited to, infective endocarditis; myocardial, peri-
domized, clinical trials; many recommendations were developed
nephric, hepatic, and splenic abscesses; septic thrombophlebitis
from observational studies or small case series, combined with
with and without pulmonary emboli [16]; necrotizing pneu-
monia [17–21]; osteomyelitis complicated by subperiosteal ab- the opinion of expert panel members.
scesses; venous thrombosis and sustained bacteremia [16, 22,
Process Overview
23]; severe ocular infections, including endophthalmitis [24];
In evaluating the evidence regarding the management of MRSA,
sepsis with purpura fulminans [25]; and Waterhouse-Frider-
the Panel followed a process used in the development of other
ichsen syndrome [26].
IDSA guidelines. The process included a systematic weighting of
The Expert Panel addressed the following clinical questions in
the quality of the evidence and the grade of recommendation
the 2010 Guidelines:
(Table 1) [28].
I. What is the management of SSTIs in the CA-MRSA era?
II. What is the management of recurrent MRSA SSTIs? Consensus Development Based on Evidence
III. What is the management of MRSA bacteremia and The Panel met on 7 occasions via teleconference to complete the
infective endocarditis? work of the guideline and at the 2007 Annual Meeting of the
IV. What is the management of MRSA pneumonia? IDSA and the 2008 Joint Interscience Conference on Antimi-
V. What is the management of MRSA bone and joint crobial Agents and Chemotherapy/IDSA Meeting. The purpose
infections? of these meetings was to discuss the questions to be addressed, to
VI. What is the management of MRSA infections of the CNS? make writing assignments, and to deliberate on the recom-
VII. What is the role of adjunctive therapies for the treatment mendations. All members of the panel participated in the
of MRSA infections? preparation and review of the draft guideline. Feedback from
VIII. What are the recommendations for vancomycin dosing external peer reviews was obtained. The guideline was reviewed
and monitoring? and endorsed by the Pediatric Infectious Diseases Society, the
IX. How should results of vancomycin susceptibility testing be American College of Emergency Physicians, and American
used to guide therapy? Academy of Pediatrics. The guideline was reviewed and ap-
X. What is the management of persistent MRSA bacteremia proved by the IDSA SPGC and the IDSA Board of Directors
and vancomycin treatment failures? prior to dissemination.
XI. What is the management of MRSA in neonates?
Guidelines and Conflict of Interest
PRACTICE GUIDELINES All members of the Expert Panel complied with the IDSA policy
on conflicts of interest, which requires disclosure of any financial
‘‘Practice guidelines are systematically developed statements to or other interest that might be construed as constituting an ac-
assist practitioners and patients in making decisions about appro- tual, potential, or apparent conflict. Members of the Expert Panel
priate health care for specific clinical circumstances’’ [27]. Attrib- were provided IDSA’s conflict of interest disclosure statement
utes of good guidelines include validity, reliability, reproducibility, and were asked to identify ties to companies developing products
clinical applicability, clinical flexibility, clarity, multidisciplinary that might be affected by promulgation of the guideline. In-
process, review of evidence, and documentation [27]. formation was requested regarding employment, consultancies,

Table 1. Strength of Recommendation and Quality of Evidence
Category/grade Definition
Strength of recommendation
A Good evidence to support a recommendation for or against use.
B Moderate evidence to support a recommendation for or against use.
C Poor evidence to support a recommendation.
Quality of evidence
I Evidence from >1 properly randomized, controlled trial.
II Evidence from >1 well-designed clinical trial, without randomization; from cohort or case-con-
trolled analytic studies (preferably from .1 center); from multiple time-series; or from dramatic
results from uncontrolled experiments.
III Evidence from opinions of respected authorities, based on clinical experience, descriptive
studies, or reports of expert committees.

NOTE. Adapted from [28]. Reproduced with the permission of the Minister of Public Works and Government Services Canada.
stock ownership, honoraria, research funding, expert testimony, dependent fashion. It is FDA-approved for adults with S. aureus
and membership on company advisory committees. The Panel bacteremia, right-sided infective endocarditis, and cSSTI. It
made decisions on a case-by-case basis as to whether an in- should not be used for the treatment of non-hematogenous
dividual’s role should be limited as a result of a conflict. Potential MRSA pneumonia, because its activity is inhibited by pulmonary
conflicts are listed in the Acknowledgements section. surfactant. It is highly protein bound (91%) and renally excreted.
The daptomycin susceptibility breakpoint for S. aureus is <1 lg/
LITERATURE REVIEW mL. Nonsusceptible isolates have emerged during therapy in as-
sociation with treatment failure [42–45]. Although the mecha-
Antimicrobial therapy nism of resistance is not clear, single-point mutations in mprF, the
Clindamycin. Clindamycin is approved by the US Food and lysylphosphatidyglycerol synthetase gene, are often present in such
Drug Administration (FDA) for the treatment of serious in- strains [46]. Prior exposure to vancomycin and elevated vanco-
fections due to S. aureus. Although not specifically approved for mycin MICs have been associated with increases in daptomycin
treatment of MRSA infection, it has become widely used for MICs, suggesting possible cross-resistance [45, 47, 48]. Elevations
treatment of SSTI and has been successfully used for treatment in creatinine phosphokinase (CPK), which are rarely treatment
of invasive susceptible CA-MRSA infections in children, in- limiting, have occurred in patients receiving 6 mg/kg/day but not
cluding osteomyelitis, septic arthritis, pneumonia, and lymph- in those receiving 4 mg/kg/day of daptomycin [49, 50]. Patients
adenitis [22, 29–31]. Because it is bacteriostatic, it is not should be observed for development of muscle pain or weakness
recommended for endovascular infections, such as infective and have weekly CPK levels determined, with more frequent
endocarditis or septic thrombophlebitis. Clindamycin has ex- monitoring in those with renal insufficiency or who are receiving
cellent tissue penetration, particularly in bone and abscesses, concomitant statin therapy. Several case reports of daptomycin-
although penetration into the CSF is limited [32–34]. In vitro induced eosinophilic pneumonia have been described [51]. The
rates of susceptibility to clindamycin are higher among CA- pharmacokinetics, safety, and efficacy of daptomycin in children
MRSA than they are among HA-MRSA [35], although there is have not been established and are under investigation [52].
variation by geographic region [29, 36, 37]. The D-zone test is Daptomycin is pregnancy category B.
recommended for detection of inducible clindamycin resistance Linezolid Linezolid is a synthetic oxazolidinone and in-
in erythromycin-resistant, clindamycin-susceptible isolates and hibits initiation of protein synthesis at the 50S ribosome. It is
is now readily available [38]. Diarrhea is the most common FDA-approved for adults and children for the treatment of
adverse effect and occurs in up to 20% of patients, and Clos- SSTI and nosocomial pneumonia due to MRSA. It has in vitro
tridium difficile–associated disease may occur more frequently, activity against VISA and VRSA [53–55]. It has 100% oral
compared with other oral agents. [39]. The oral suspension is bioavailability; hence, parenteral therapy should only be given if
often not well tolerated in children, although this may be there are problems with gastrointestinal absorption or if the
overcome with addition of flavoring [40]. It is pregnancy cate- patient is unable to take oral medications. Linezolid resistance is
gory B [41]. rare, although an outbreak of linezolid-resistant MRSA infection
Daptomycin. Daptomycin is a lipopeptide class antibiotic has been described [56]. Resistance typically occurs during
that disrupts cell membrane function via calcium-dependent prolonged use via a mutation in the 23S ribosomal RNA (rRNA)
binding, resulting in bactericidal activity in a concentration- binding site for linezolid [57] or cfr gene-mediated methylation

of adenosine at position 2503 in 23SrRNA [58, 59]. Long-term in 2 clinical trials [75]; monitoring of serum levels is not avail-
use is limited by hematologic toxicity, with thrombocytopenia able.
occurring more frequently than anemia and neutropenia, pe- Tetracyclines. Doxycycline is FDA-approved for the
ripheral and optic neuropathy, and lactic acidosis. Although treatment of SSTI due to S. aureus, although not specifically
myelosuppression is generally reversible, peripheral and optic for those caused by MRSA. Although tetracyclines have in
neuropathy are not reversible or are only partially reversible vitro activity, data on the use of tetracyclines for the treatment
[60]. Linezolid is a weak, nonselective, reversible inhibitor of of MRSA infections are limited. Tetracyclines appear to be
monoamine oxidase and has been associated with serotonin effective in the treatment of SSTI, but data are lacking to
syndrome in patients taking concurrent selective serotonin- support their use in more-invasive infections [76]. Tetracy-
receptor inhibitors [61]. Linezolid causes less bone marrow cline resistance in CA-MRSA isolates is primarily associated
suppression in children than it causes in adults [62]. The most with tetK [77]. Although the tet(M) gene confers resistance to
common adverse events in children are diarrhea, vomiting, loose all agents in the class, tet(K) confers resistance to tetracycline
stools, and nausea [63]. The linezolid suspension may not be [78] and inducible resistance to doxycycline [79], with no

tolerated because of taste and may not be available in some impact on minocycline susceptibility. Therefore, minocycline
pharmacies. It is considered pregnancy category C. may be a potential alternative in such cases. Minocycline is
Quinupristin-Dalfopristin. Quinupristin-dalfopristin is available in oral and parenteral formulations. Tigecycline is
a combination of 2 streptogramin antibiotics and inhibits pro- a glycylcycline, a derivative of the tetracyclines, and is FDA-
tein synthesis. It is FDA-approved for cSSTI in adults and approved in adults for cSSTIs and intraabdominal infections.
children .16 years of age. It has been used as salvage therapy for It has a large volume of distribution and achieves high
invasive MRSA infections in the setting of vancomycin treat- concentrations in tissues and low concentrations in serum
ment failure in adults and children [64–66]. Toxicity, including (,1 lg/mL) [80]. For this reason, and because it exhibits
arthralgias, myalgias, nausea, and infusion-related reactions, has bacteriostatic activity against MRSA, caution should be used
limited its use. Quinupristin-dalfopristin is considered preg- in treating patients with bacteremia. The FDA recently issued
nancy category B. a warning to consider alternative agents in patients with se-
Rifampin. Rifampin has bactericidal activity against S. au- rious infections because of an increase in all-cause mortality
reus and achieves high intracellular levels, in addition to pene- noted across phase III/IV clinical trials. Tetracyclines
trating biofilms [67–69]. Because of the rapid development of are pregnancy category D and are not recommended for
resistance, it should not be used as monotherapy but may be children ,8 years of age because of the potential for tooth
used in combination with another active antibiotic in selected enamel discoloration and decreased bone growth.
scenarios. The role of rifampin as adjunctive therapy in MRSA TMP-SMX. TMP-SMX is not FDA-approved for the
infections has not been definitively established, and there is treatment of any staphylococcal infections. However, because
a lack of adequately powered, controlled clinical studies in the 95%–100% of CA-MRSA strains are susceptible in vitro [81, 82],
literature [120]. The potential use of rifampin as adjunctive it has become an important option for the outpatient treatment
therapy for MRSA infections is discussed in various sections of SSTI [83–85]. A few studies, primarily involving methicillin-
throughout these guidelines. Of note, rifampin dosing is quite susceptible S. aureus (MSSA), have suggested a role in bone and
variable throughout the literature, ranging from 600 mg daily in joint infections [86–88]. A few case reports [89] and 1 ran-
a single dose or in 2 divided doses to 900 mg daily in 2 or 3 domized trial indicate potential efficacy in treating invasive
divided doses [70–74]. The range of rifampin dosing in these staphylococcal infections, such as bacteremia and endocarditis
guidelines is suggested on the basis of the limited published data [90]. TMP-SMX is effective for the treatment of purulent SSTI
and is considered reasonable on the basis of expert opinion. in children [91]. It has not been evaluated for the treatment of
Additional study is needed to define the role and optimal dosing invasive CA-MRSA infections in children. Caution is advised
of rifampin in management of MRSA infections. when using TMP-SMX to treat elderly patients, particularly
Telavancin. Telavancin is a parenteral lipoglycopeptide those receiving concurrent inhibitors of the renin-angiotensin
that inhibits cell wall synthesis by binding to peptidoglycan system and those with chronic renal insufficiency, because of an
chain precursors, causing cell membrane depolarization [75]. It increased risk of hyperkalemia [92]. TMP-SMX is not recom-
is bactericidal against MRSA, VISA, and VRSA. It is FDA-ap- mended in pregnant women in the third trimester, when it is
proved for cSSTI in adults and is pregnancy category C. Cre- considered pregnancy category C/D, or in infants younger than
atinine levels should be monitored, and dosage should be 2 months of age.
adjusted on the basis of creatinine clearance, because nephro- Vancomycin. Vancomycin has been the mainstay of par-
toxicity was more commonly reported among individuals trea- enteral therapy for MRSA infections. However, its efficacy has
ted with telavancin than among those treated with vancomycin come into question, with concerns over its slow bactericidal

activity, the emergence of resistant strains, and possible ‘‘MIC (A-II), TMP-SMX (A-II), a tetracycline (doxycycline or
creep’’ among susceptible strains [93–95]. Vancomycin kills minocycline) (A-II), and linezolid (A-II). If coverage for both
staphylococci more slowly than do b-lactams in vitro, particu- b-hemolytic streptococci and CA-MRSA is desired, options
larly at higher inocula (107–109 colony-forming units) [96] and include the following: clindamycin alone (A-II) or TMP-SMX
is clearly inferior to b-lactams for MSSA bacteremia and infective or a tetracycline in combination with a b-lactam (eg,
endocarditis [97–101]. Tissue penetration is highly variable and amoxicillin) (A-II) or linezolid alone (A-II).
depends upon the degree of inflammation. In particular, it has 6. The use of rifampin as a single agent or as adjunctive
limited penetration into bone [102], lung epithelial lining fluid therapy for the treatment of SSTI is not recommended (A-III).
[103] and CSF [104, 105]. Vancomycin is considered pregnancy 7. For hospitalized patients with complicated SSTI (cSSTI:
category C [41]. Vancomycin dosing, monitoring, and suscep- defined as patients with deeper soft-tissue infections, surgical/
tibility testing are discussed in Sections VIII and IX.3 traumatic wound infection, major abscesses, cellulitis, and
infected ulcers and burns) SSTI, in addition to surgical
debridement and broad-spectrum antibiotics, empirical ther-

RECOMMENDATIONS FOR THE MANAGEMENT apy for MRSA should be considered pending culture data.
OF PATIENTS WITH INFECTIONS CAUSED BY Options include the following: IV vancomycin (A-I), linezolid
MRSA 600 mg PO/IV twice daily (A-I), daptomycin 4 mg/kg/dose IV
once daily (A-I), telavancin 10 mg/kg/dose IV once daily (A-I),
I. What is the management of SSTIs in the era of CA-MRSA? clindamycin 600 mg IV/PO three times a day (A-III). A
SSTI b-lactam antibiotic (eg, cefazolin) may be considered in
hospitalized patients with nonpurulent cellulitis with modifi-
1. For a cutaneous abscess, incision and drainage is the
cation to MRSA-active therapy if there is no clinical response
primary treatment (A-II). For simple abscesses or boils,
(A-II). Seven to 14 days of therapy is recommended but should
incision and drainage alone is likely adequate but additional
be individualized on the basis of the patient’s clinical response.
data are needed to further define the role of antibiotics, if any,
8. Cultures from abscesses and other purulent SSTI are
in this setting.
recommended in patients treated with antibiotic therapy,
2. Antibiotic therapy is recommended for abscesses associated
patients with severe local infection or signs of systemic illness,
with the following conditions: severe or extensive disease (eg,
patients who have not responded adequately to initial treatment,
involving multiple sites of infection) or rapid progression in
and if there is concern for a cluster or outbreak (A-III).
presence of associated cellulitis, signs and symptoms of
systemic illness, associated comorbidities or immunosuppres- Pediatric considerations
sion, extremes of age, abscess in area difficult to drain (eg, face,
9. For children with minor skin infections (such as impetigo) and
hand, and genitalia), associated septic phlebitis, lack of
secondarily infected skin lesions (such as eczema, ulcers, or
response to I &D alone (A-III).
lacerations), mupirocin 2% topical ointment can be used (A-III).
3. For outpatients with purulent cellulitis (eg, cellulitis
10. Tetracyclines should not be used in children ,8 years of
associated with purulent drainage or exudate in the absence of
age (A-II).
a drainable abscess), empirical therapy for CA-MRSA is
11. In hospitalized children with cSSTI, vancomycin is
recommended pending culture results. Empirical therapy for
recommended (A-II). If the patient is stable without ongoing
infection due to b-hemolytic streptococci is likely unnecessary
bacteremia or intravascular infection, empirical therapy with
(A-II). Five to 10 days of therapy is recommended but should
clindamycin 10–13 mg/kg/dose IV every 6–8 h (to administer
be individualized on the basis of the patient’s clinical
40 mg/kg/day) is an option if the clindamycin resistance rate is
response.
low (eg, ,10%) with transition to oral therapy if the strain is
4. For outpatients with nonpurulent cellulitis (eg, cellulitis
susceptible (A-II). Linezolid 600 mg PO/IV twice daily for
with no purulent drainage or exudate and no associated
children >12 years of age and 10 mg/kg/dose PO/IV every 8 h
abscess), empirical therapy for infection due to b-hemolytic
for children ,12 years of age is an alternative (A-II).
streptococci is recommended (A-II). The role of CA-MRSA is
unknown. Empirical coverage for CA-MRSA is recommended Evidence Summary
in patients who do not respond to b-lactam therapy and may be The emergence of CA-MRSA has led to a dramatic increase in
considered in those with systemic toxicity. Five to 10 days of emergency department visits and hospital admissions for SSTIs
therapy is recommended but should be individualized on the [106, 107]. For minor skin infections (such as impetigo) and
basis of the patient’s clinical response. secondarily infected skin lesions (such as eczema, ulcers, or
5. For empirical coverage of CA-MRSA in outpatients with lacerations), mupirocin 2% topical ointment may be effective.
SSTI, oral antibiotic options include the following: clindamycin For cutaneous abscesses, the main treatment is incision and

drainage [108]. For small furuncles, moist heat, which helps to although MRSA susceptibility rates may vary by region [85, 124,
promote drainage, may be sufficient [109]. It remains contro- 125]. The D-zone test is recommended for erythromycin-re-
versial whether antibiotics provide any clinically significant ad- sistant, clindamycin-susceptible isolates to detect inducible
ditional benefit, but incision and drainage is likely adequate for clindamycin resistance. The clinical significance of inducible
most simple abscesses. Multiple, mostly observational studies clindamycin resistance is unclear because the drug may still be
indicate high cure rates (85%–90%) whether or not an active effective for some patients with mild infections; however, its
antibiotic is used [11, 81, 110–112]. Two recently published presence should preclude the use of clindamycin for more-se-
randomized clinical trials involving adult [113] and pediatric rious infections.
[114] patients showed no significant difference in cure rates Outpatients presenting with purulent cellulitis (cellulitis as-
when TMP-SMX was compared with placebo; however, there sociated with purulent drainage or exudate in the absence of
was a suggestion that antibiotics may prevent the short-term a drainable abscess) should empirically receive oral antibiotics
development of new lesions. Two retrospective studies suggest active against CA-MRSA while awaiting culture data. Among
improved cure rates if an effective antibiotic is used [85, 115]. patients presenting with purulent SSTI to 11 emergency de-

We hope that additional prospective, large-scale studies that are partments throughout the United States, CA-MRSA was the
currently already underway will provide more-definitive answers dominant organism, isolated from 59% of patients, followed by
to these questions. Antibiotic therapy is recommended for ab- MSSA (17%); b- hemolytic streptococci accounted for a much
scesses associated with the conditions listed in Table 2 [83, 116]. small proportion (2.6%) of these infections [11]. In non-
Oral antibiotics that may be used as empirical therapy for CA- purulent cellulitis (cellulitis with no purulent drainage or exu-
MRSA include TMP-SMX, doxycycline (or minocycline), clin- date and no associated abscess), ultrasound may be considered
damycin, and linezolid. Several observational studies [85, 117] to exclude occult abscess [126, 127]. For nonpurulent cellulitis,
and one small randomized trial [84] suggest that TMP-SMX, the absence of culturable material presents an inherent challenge
doxycycline, and minocycline are effective for such infections. to our ability to determine its microbiologic etiology and make
Clindamycin is effective in children with CA-MRSA SSTI [91, decisions regarding empirical antibiotic therapy. In the pre–CA-
118]. Linezolid is FDA-approved for SSTI but is not superior MRSA era, microbiologic investigations using needle aspiration
to less expensive alternatives [119]. Because of the likely de- or punch biopsy cultures of nonpurulent cellulitis identified
velopment of resistance, rifampin should not be used as mon- b-hemolytic streptococci and S. aureus as the main pathogens.
otherapy for the treatment of MRSA infections. The adjunctive In the majority of cases, a bacterial etiology was not identified,
use of rifampin with another active drug for the treatment of but MSSA was the most common pathogen among those who
SSTI is not recommended in the absence of data to support were culture positive [128–133]. A retrospective case-control
benefit [120]. study in children with nonpurulent cellulitis found that, com-
The need to include coverage against b-hemolytic strepto- pared with b-lactams, clindamycin provided no additional
cocci in addition to CA-MRSA is controversial and may vary benefit, whereas TMP-SMX was associated with a slightly higher
depending on local epidemiology and the type of SSTI as dis- failure rate [134]. The only prospective study of nonculturable
cussed below. Although TMP-SMX, doxycycline, and minocy- cellulitis among hospitalized inpatients found that b-hemolytic
cline have good in vitro activity against CA-MRSA, their activity streptococci (diagnosed by acute- and convalescent-phase se-
against b- hemolytic streptococci is not well-defined [121–123]. rological testing for anti-streptolysin-O and anti-DNase-B an-
Clindamycin is active against b- hemolytic streptococci, tibodies or positive blood culture results) accounted for 73% of
the cases; despite the lack of an identifiable etiology in 27% of
Table 2. cases, the overall clinical response rate to b-lactam therapy was
96% [135]. Although additional research is needed to charac-
Conditions in which Antimicrobial Therapy is Recommended after
Incision and Drainage of an Abscess due to Community-Associated terize the microbiology of nonpurulent cellulitis, currently
Methicillin-Resistant Staphylococcus aureus available data suggests that b-hemolytic streptococci may be the
Severe or extensive disease (eg, involving multiple sites of primary pathogen. The relative contribution of CA-MRSA,
infection) or rapid progression in presence of associated cellulitis compared with b-hemolytic streptococci and MSSA, remains
Signs and symptoms of systemic illness unknown, but empirical coverage for CA-MRSA is recom-
Associated comorbidities or immunosuppression (diabetes mended in those who have not responded to b-lactam mono-
mellitus, human immunodeficiency virus infection/AIDS, neoplasm)
Extremes of age therapy and may be considered in those with systemic toxicity.
Abscess in area difficult to drain completely (eg, face, hand, For patients with systemic toxicity and/or rapidly progressive
and genitalia) or worsening infection despite receipt of appropriate oral anti-
Associated septic phlebitis biotics, inpatient management and surgical intervention is rec-
Lack of response to incision and drainage alone ommended. Several antibiotics with MRSA activity are FDA-

Table 3. Recommendations for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA)
Manifestation Treatment Adult dose Pediatric dose Classa Comment

Skin and soft-tissue
infection (SSTI)
Abscess, furuncles, Incision and drainage AII For simple abscesses or boils,
carbuncles incision and drainage is likely
adequate. Please refer to
Table 2 for conditions in
which antimicrobial therapy
is recommended after
incision and drainage of an
abscess due to CA-MRSA.
Purulent cellulitis Clindamycin 300–450 mg PO TID 10–13 mg/kg/dose PO every AII Clostridium difficile–associated
(defined as cellulitis 6–8 h, not to exceed disease may occur more
associated with purulent 40 mg/kg/day frequently, compared with
drainage or exudate in other oral agents.
the absence of a drainable
abscess)
TMP-SMX 1–2 DS tab PO BID Trimethoprim 4–6 mg/kg/dose, AII TMP-SMX is pregnancy
sulfamethoxazole category C/D and not rec
20–30 mg/kg/dose ommended for women in
PO every 12 h the third trimester of
pregnancy and for children
,2 months of age.
Doxycycline 100 mg PO BID <45kg: 2 mg/kg/dose PO AII Tetracyclines are not
every 12 h .45kg: recommended for
adult dose children under 8 years of
age and are pregnancy
category D.
Minocycline 200 mg 3 1, then 4 mg/kg PO 3 1, then AII
100 mg PO BID 2 mg/kg/dose PO every 12 h
Linezolid 600 mg PO BID 10 mg/kg/dose PO every AII More expensive compared
8 h, not to exceed 600 with other alternatives
mg/dose
Nonpurulent cellulitis b-lactam (eg, cephalexin 500 mg PO QID Please refer to Red Book AII Empirical therapy for
(defined as cellulitis with and dicloxacillin) b-hemolytic streptococci is
no purulent drainage recommended (AII). Empirical
or exudate and no coverage for CA-MRSA is rec-
MRSA Treatment Guidelines

d
associated abscess) ommended in patients who do
not respond to b-lactam ther-
apy and may be considered in
those with systemic toxicity.
Clindamycin 300–450 mg PO TID 10–13 mg/kg/dose PO every AII Provide coverage for both
6–8 h, not to exceed b-hemolytic streptococci and
40 mg/kg/day CA-MRSA
b-lactam (eg, amoxicillin) Amoxicillin: 500 PO mg TID Please refer to Red Book AII Provide coverage for both
and/or TMP-SMX or a See above for TMP-SMX See above for TMP- b-hemolytic streptococci
tetracycline and tetracycline dosing SMX and tetracycline dosing and CA-MRSA
CID 2011:52 (1 February)

Linezolid 600 mg PO BID 10 mg/kg/dose PO every 8 h, not AII
d
to exceed 600 mg/dose
e29
Table 3. (Continued)
e30 d
Provide coverage for both
B-hemolytic streptococci
and CA-MRSA
Complicated SSTI Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AI/AII
8–12 h
Linezolid 600 mg PO/IV BID 10 mg/kg/dose PO/IV every AI/AII For children >12 years of age,
8 h, not to exceed 600 mg PO/IV BID. Pregnancy
600 mg/dose category C
Daptomycin 4 mg/kg/dose IV QD Ongoing study AI/ND The doses under study in

d
children are 5 mg/kg (ages 12–
17 years), 7 mg/kg (ages 7–11
years), 9 mg/kg (ages 2–6
years) (Clinicaltrials.gov NCT
Liu et al
00711802). Pregnancy cate-
gory B.
Telavancin 10 mg/kg/dose IV QD ND AI/ND Pregnancy category C
Clindamycin 600 mg PO/IV TID 10–13 mg/kg/dose PO/IV every AIII/AII Pregnancy category B
6–8 h, not to exceed
40 mg/kg/day
Bacteremia and infective
endocarditis
Bacteremia Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AII The addition of gentamicin (AII)
8–12 h or rifampin (AI) to vancomycin
is not routinely recommended.
Daptomycin 6 mg/kg/dose IV QD 6–10 mg/kg/dose IV QD AI/CIII For adult patients, some
experts recommend higher
dosages of 8–10 mg/kg/dose
IV QD (BIII). Pregnancy cate-
gory B.
Infective endocarditis, Same as for bacteremia
native valve
Infective endocarditis, Vancomycin and 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BIII
prosthetic valve gentamicin and rifampin 8–12 h
1 mg/kg/dose IV every 8 h 1 mg/kg/dose IV every 8 h
300 mg PO/IV every 8 h 5 mg/kg/dose PO/IV every 8 h
Persistent bacteremia Please see text
Pneumonia
Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AII
8–12 h
Linezolid 600 mg PO/IV BID 10 mg/kg/dose PO/IV every 8 h, AII For children >12 years,
not to exceed 600 mg/dose 600 mg PO/IV BID. Pregnancy
category C.
Clindamycin 600 mg PO/IV TID 10–13 mg/kg/dose PO/IV every BIII/AII Pregnancy category B.
6–8 h, not to exceed 40 mg/kg/
day

Bone and joint infections

Osteomyelitis Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII/AII Surgical debridement and
8–12 h drainage of associated soft-
tissue abscesses is the
mainstay of therapy. (AII).
Some experts recommend the
addition of rifampin 600 mg
QD or 300–450 mg BID to the
chosen antibiotic (BIII). For
children >12 years of age,
linezolid 600 mg PO/IV BID
should be used. A single-
strength and DS tablet of
TMP-SMX contains 80 mg and
160 mg of TMP, respectively.
For an 80-kg adult, 2 DS tab-
lets achieves a dose of 4 mg/
kg.
Daptomycin 6 mg/kg/day IV QD 6–10 mg/kg/day IV QD BII/CIII
Linezolid 600 mg PO/IV BID 10 mg/kg/dose PO/IV every BII/CIII
8 h, not to exceed
600 mg/dose
Clindamycin 600 mg PO/IV TID 10–13 mg/kg/dose PO/IV every BIII/AII
40 mg/kg/day
TMP-SMX and rifampin 3.5–4.0 mg/kg/dose PO/IV ND BII/ND
every 8–12 h
600 mg PO QD
Septic arthritis Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII/AII Drainage or debridement of
8–12 h the joint space should always
be performed (AII).
Daptomycin 6 mg/kg/day IV QD 6–10 mg/kg/dose IV QD BII/CIII
Linezolid 600 mg PO/IV BID 10 mg/kg/dose PO/IV every BII/CIII
8 h, not to exceed
MRSA Treatment Guidelines

600 mg/dose
d
Clindamycin 600 mg PO/IV TID 10–13 mg/kg/dose PO/IV every BIII/AII
40 mg/kg/day
TMP-SMX 3.5–4.0 mg/kg/dose PO/IV ND BIII/ND
every 8–12 h
Prosthetic joint, spinal Please see text
implant infections
Central nervous system
infections

e31 d
e32 d
Meningitis Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
8–12 h addition of rifampin 600 mg

QD or 300–450 mg BID to
d
vancomycin for adult patients
(BIII). For children >12 years
of age, linezolid 600 mg BID.
Liu et al
Linezolid 600 mg PO/IV BID 10 mg/kg/dose PO/IV every BII
8 h, not to exceed
600 mg/dose
TMP-SMX 5 mg/kg/dose PO/IV every ND CIII/ND
8-12 h
Brain abscess, subdural Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
empyema, spinal 8–12 h addition of rifampin 600 mg
epidural abscess QD or 300–450 mg BID to
of age, linezolid 600 mg BID.
8 h, not to exceed
600 mg/dose
TMP-SMX 5 mg/kg/dose PO/IV ND CIII/ND
every 8–12 h
Septic thrombosis of Vancomycin 15–20 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
cavernous or dural 8–12 h addition of rifampin 600 mg
venous sinus QD or 300–450 mg BID to
of age, linezolid 600 mg BID
8 h, not to exceed
600 mg/dose
TMP-SMX 5 mg/kg/dose PO/IV every ND CIII/ND
8-12 h
NOTE. BID, twice daily; CA-MRSA, community-associated MRSA; DS, double strength; IV, intravenous; ND, no data; PO, oral; QD, every day; TID, 3 times per day; TMP-SMX, trimethoprim-sulfamethoxazole.
a
Classification of the strength of recommendation and quality of evidence applies to adult and pediatric patients unless otherwise specified. A backslash (/) followed by the recommendation strength and evidence
grade will denote any differences in pediatric classification.

approved for the treatment of adult patients with cSSTI, such as 14. Decolonization may be considered in selected cases if:
deep soft-tissue infections, surgical and/or traumatic wound
i. A patient develops a recurrent SSTI despite optimizing
infections, major abscesses, cellulitis, infected ulcers, and burns:
wound care and hygiene measures (C-III).
vancomycin, linezolid, daptomycin, tigecycline, and telavancin
ii. Ongoing transmission is occurring among household
[50, 136–138]. Because of a recent FDA warning indicating an
members or other close contacts despite optimizing wound
increased risk in all-cause mortality with tigecycline versus
care and hygiene measures (C-III).
comparator drugs in a pooled analysis of clinical trials, the drug
was not included in these guidelines, given the availability of 15. Decolonization strategies should be offered in conjunction
multiple MRSA-active alternatives. Ceftaroline, a novel cepha- with ongoing reinforcement of hygiene measures and may
losporin antibiotic, may become available in the near future for include the following:
treatment of cSSTI, pending FDA review. When compared with i. Nasal decolonization with mupirocin twice daily for 5–10
vancomycin, none of these newer agents have demonstrated days (C-III).
superiority in the primary outcome of clinical cure. There are

ii. Nasal decolonization with mupirocin twice daily for 5–
limited published data on the use of clindamycin in adults with 10 days and topical body decolonization regimens with
cSSTI due to MRSA. Options for the treatment of cSSTI in a skin antiseptic solution (eg, chlorhexidine) for 5–14 days
children include clindamycin and linezolid [13, 139]. For hos- or dilute bleach baths. (For dilute bleach baths, 1 teaspoon
pitalized patients with a nonpurulent cellulitis, a b-lactam an- per gallon of water [or ¼ cup per ¼ tub or 13 gallons of
tibiotic (eg, cefazolin) can be considered with modification to water] given for 15 min twice weekly for 3 months can be
a MRSA-active agent if there is no clinical response [135]. considered.) (C-III).
The duration of therapy for SSTI has not been well-defined,
16. Oral antimicrobial therapy is recommended for the
although no differences in outcome were observed among adult
treatment of active infection only and is not routinely
patients with uncomplicated cellulitis receiving 5 versus 10 days
recommended for decolonization (A-III). An oral agent in
of therapy in a randomized, controlled trial [140]. In the FDA
combination with rifampin, if the strain is susceptible, may be
licensing trials for cSSTI, patients were typically treated for 7–14
considered for decolonization if infections recur despite above
days. Duration of therapy should be individualized on the basis
measures (CIII).
of the patient’s clinical response.
17. In cases where household or interpersonal transmission is
II. What is the management of recurrent MRSA SSTIs? suspected:
Recurrent SSTIs i. Personal and environmental hygiene measures in the
12. Preventive educational messages on personal hygiene and patient and contacts are recommended (A-III).
appropriate wound care are recommended for all patients with ii. Contacts should be evaluated for evidence of S. aureus
SSTI. Instructions should be provided to: infection:
a. Symptomatic contacts should be evaluated and treated
i. Keep draining wounds covered with clean, dry bandages
(A-III); nasal and topical body decolonization strategies
(A-III).
may be considered following treatment of active infection
ii. Maintain good personal hygiene with regular bathing and
(C-III).
cleaning of hands with soap and water or an alcohol-based
b. Nasal and topical body decolonization of asymptomatic
hand gel, particularly after touching infected skin or an item
household contacts may be considered (C-III).
that has directly contacted a draining wound (A-III).
iii. Avoid reusing or sharing personal items (eg, disposable 18. The role of cultures in the management of patients with
razors, linens, and towels) that have contacted infected skin (A-III). recurrent SSTI is limited:
13. Environmental hygiene measures should be considered in i. Screening cultures prior to decolonization are not
patients with recurrent SSTI in the household or community routinely recommended if at least 1 of the prior infections
setting: was documented as due to MRSA (B-III).
ii. Surveillance cultures following a decolonization regimen
i. Focus cleaning efforts on high-touch surfaces (ie, surfaces
are not routinely recommended in the absence of an active
that come into frequent contact with people’s bare skin each
infection (B-III).
day, counters, door knobs, bath tubs, and toilet seats) that may
contact bare skin or uncovered infections (C-III). Evidence Summary
ii. Commercially available cleaners or detergents appropriate There are few studies to guide the development of evidence-
for the surface being cleaned should be used according to label based recommendations on the management of recurrent CA-
instructions for routine cleaning of surfaces (C-III). MRSA SSTI. Although no standardized definition exists, most

experts define recurrent disease as 2 or more discrete SSTI ep- commercial tests in the United States, we are unable to provide
isodes at different sites over a 6-month period. The pathogenesis specific recommendations on mupirocin susceptibility testing
of recurrent infection is unclear and likely involves a complex for individual patients at this time. Clinical laboratories that wish
interplay between the pathogen, host colonization, patient be- to perform susceptibility testing may consider validating in-
havior, and environmental exposures [141]. The Panel suggests house prepared assays, such as polymerase chain reaction or disk
a multifaceted approach that actively engages the patient in diffusion assays [152]. The role of other colonization sites in the
personal and environmental hygiene measures applicable to the development of infection or recurrent disease is unknown, and
household or community setting [142] while accounting for eliminating nasal colonization alone may be insufficient. Colo-
individual preferences. Infected skin and draining wounds nization at nonnasal sites, such as the groin, axilla, and rectum, is
should be covered, and sharing of personal items should be more common among those with CA-MRSA than it is among
avoided. Commercially available cleaners or detergents should those with CA-MSSA or HA-MRSA [153], although it may be
be used for surfaces that come into frequent contact with peo- difficult to distinguish true colonization from transient con-
ple’s bare skin each day. tamination at these sites because of active infection.

Given the potential role of colonization in the pathogenesis of The potential effectiveness of topical skin antiseptics, such as
recurrent SSTI, prevention strategies have also focused on de- chlorhexidine and hexachlorophene, is extrapolated from data
colonization, the use of antimicrobial or antiseptic agents to on community outbreaks whereby, when bundled together with
suppress or eliminate S. aureus carriage as a means of preventing other interventions, it prevents ongoing transmission and in-
auto-infection or transmission. Decolonization measures may fection [154–158]. When used alone, chlorhexidine does not
be considered for patients with multiple recurrent SSTI despite appear to be effective; a recent randomized trial found no im-
hygiene measures or when there is ongoing transmission in pact of chlorhexidine-impregnated wipes on SSTI rates [159],
a well-defined, closely associated cohort [83]. Although de- and at best, it appears to have a transient effect on colonization,
colonization strategies are frequently employed, there are no with recolonization occurring soon after discontinuation [161].
published data to support its efficacy in patients with recurrent Hexachlorophene should not be used in infants ,2 months of
MRSA SSTI. The optimal regimen, frequency of application, and age, because it has been linked to adverse neurological outcomes
duration of therapy are unclear. Furthermore, it is unknown in newborns. The addition of bleach to bath water has previously
whether it will select for or result in replacement with more- been used for treatment of recurrent SSTI in children with ec-
resistant or more-virulent strains. zema [162]. In vitro sodium hypochlorite at a concentration
Although mupirocin appears to be effective in reducing equivalent to 1/2 cup of bleach in 1/4 tub (13 gallons) of water
MRSA colonization, it has not conclusively been shown to pre- kills CA-MRSA after 5 min [163]. Some experts suggest that
vent infections among nasal carriers [143, 144], although most bleach baths at a concentration of 1 teaspoon per gallon of bath
studies have included patients in the health care setting, where water (1/4 cup per 1/4 tub of water) for 15 min given twice
evidence for benefit is limited to certain high-risk populations. A weekly for 3 months is well-tolerated and may be effective.
Cochrane Review found that mupirocin was associated with Given the potential for skin irritation if not adequately diluted,
a reduction in nosocomial S. aureus (mostly MSSA) infections, clear instructions should be provided.
primarily among patients undergoing surgical procedures or No clinical trials have evaluated the role of oral antimicrobials
receiving dialysis [145]. No benefit was seen in the 2 studies that for treatment of recurrent CA-MRSA SSTI. A Cochrane review
included nonsurgical patients and MRSA carriers [146, 147]. The found no benefit of oral antibiotics for eradication of MRSA
combination of mupirocin and chlorhexidine soap reduced the colonization among patients in the health care setting when
rate of surgical site infections among MSSA nasal carriers [148]. compared with placebo, no treatment, or topical antibiotics;
Only 1 small clinical trial examined the role of mupirocin in the none of these studies examined their impact on infection rates
management of recurrent MSSA SSTI; a 5-day course of mu- [164]. A systematic review of comparative controlled trials
pirocin, followed by repeated application on a monthly basis for found that a rifampin-based combination, compared with
1 year, reduced the prevalence of nasal colonization and the monotherapy with other oral antibiotics, was more likely to
number of cases of recurrent SSTI [149]. A trial conducted in the eradicate S. aureus carriage, but again, no studies examined
era of CA-MRSA found that, although mupirocin decreased the infection rates as an outcome [165]. Both reviews noted the
prevalence of nasal colonization, it did not reduce the incidence emergence of rifampin resistance and adverse events associated
of first-time SSTI, compared with placebo [150]. Although it with systemic agents.
does not appear to be widespread, a high prevalence of mupir- While awaiting guidance from ongoing clinical trials, the
ocin resistance has been reported among MRSA isolates in some Panel suggests mupirocin alone or a combined strategy of mu-
community settings [151]. Because of the lack of FDA break- pirocin and topical antiseptics (eg, chlorhexidine and diluted
points for mupirocin, along with limited availability of bleach baths) if decolonization is being considered. The optimal

dosage and duration of such regimens is unknown; suggested abscess, new heart block, or persistent fevers or bacteremia
dosages are based on several ongoing clinical trials [166–168]. are present (A-II).
Oral antimicrobials are not routinely recommended for de-
Infective Endocarditis, Prosthetic Valve
colonization; they should only be considered in patients who
continue to have infections in spite of the other measures. If 27. IV vancomycin plus rifampin 300 mg PO/IV every 8 h for
prescribed for decolonization, the optimal regimen and dura- at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h for 2
tion is unknown, although a rifampin-based combination (eg, weeks (B-III).
with TMP-SMX or doxycycline) is suggested and administered 28. Early evaluation for valve replacement surgery is
in short courses (eg, 5–10 days) to decrease the potential for recommended (A-II).
development of resistance. Hygiene measures should be re-
inforced, and the oral regimen may be offered in conjunction
with a topical antiseptic, such as chlorhexidine [169]. Additional 29. In children, vancomycin 15 mg/kg/dose IV every 6 h is
studies are needed to guide the prevention of recurrent SSTI. recommended for the treatment of bacteremia and infective

endocarditis (A-II). Duration of therapy may range from 2 to 6
III. What is the management of MRSA bacteremia and infective weeks depending on source, presence of endovascular infection,
endocarditis? and metastatic foci of infection. Data regarding the safety and
Bacteremia and Infective Endocarditis, Native Valve efficacy of alternative agents in children are limited, although
daptomycin 6–10 mg/kg/dose IV once daily may be an option
19. For adults with uncomplicated bacteremia (defined as
(C-III). Clindamycin or linezolid should not be used if there is
patients with positive blood culture results and the following:
concern for infective endocarditis or endovascular source of
exclusion of endocarditis; no implanted prostheses; follow-up
infection but may be considered in children whose bacteremia
blood cultures performed on specimens obtained 2–4 days after
rapidly clears and is not related to an endovascular focus (B-
the initial set that do not grow MRSA; defervescence within 72 h
III).
of initiating effective therapy; and no evidence of metastatic sites
30. Data are insufficient to support the routine use of
of infection), vancomycin (A-II) or daptomycin 6 mg/kg/dose
combination therapy with rifampin or gentamicin in children
IV once daily (AI) for at least 2 weeks. For complicated
with bacteremia or infective endocarditis (C-III); the decision
bacteremia (defined as patients with positive blood culture
to use combination therapy should be individualized.
results who do not meet criteria for uncomplicated bacteremia),
31. Echocardiogram is recommended in children with
4–6 weeks of therapy is recommended, depending on the extent
congenital heart disease, bacteremia more than 2–3 days in
of infection. Some experts recommend higher dosages of
duration, or other clinical findings suggestive of endocarditis
daptomycin at 8–10 mg/kg/dose IV once daily (B-III).
(A-III).
20. For adults with infective endocarditis, IV vancomycin (A-
II) or daptomycin 6 mg/kg/dose IV once daily (A-I) for 6 weeks Evidence Summary
is recommended. Some experts recommend higher dosages of MRSA bacteremia and infective endocarditis are serious diseases
daptomycin at 8–10 mg/kg/dose IV once daily (B-III). associated with high morbidity, and mortality rates are 30%–
21. Addition of gentamicin to vancomycin is not recommen- 37% for MRSA endocarditis [170, 171]. In addition to antimi-
ded for bacteremia or native valve infective endocarditis (A-II). crobial therapy, the source and extent of infection, including
22. Addition of rifampin to vancomycin is not recommended embolic or metastatic foci, should be determined through
for bacteremia or native valve infective endocarditis (A-I). careful history and physical examination and imaging, with re-
23. A clinical assessment to identify the source and extent of moval or debridement whenever possible. Vancomycin has been
the infection with elimination and/or debridement of other the mainstay of therapy for MRSA bacteremia and endocarditis.
sites of infection should be conducted (A-II). However, compared with b-lactam agents, vancomycin is less
24. Additional blood cultures 2–4 days after initial positive effective for the treatment of MSSA bacteremia and endocarditis
cultures and as needed thereafter are recommended to [98, 99]. Although rifampin or gentamicin is occasionally used
document clearance of bacteremia (A-II). in combination with vancomycin to improve outcomes, clinical
25. Echocardiography is recommended for all adult patients data do not support this practice. In one study, the duration of
with bacteremia. TEE is preferred over TTE (A-II). bacteremia was longer in the rifampin-combination therapy
26. Evaluation for valve replacement surgery is recommended group than in the vancomycin monotherapy group [172]. The
if large vegetation (.10 mm in diameter), occurrence of >1 use of rifampin combination therapy in a study of native valve S.
embolic event during the first 2 weeks of therapy, severe aureus endocarditis did not improve outcomes but was associ-
valvular insufficiency, valvular perforation or dehiscence, ated with hepatic adverse effects, drug interactions, and the
decompensated heart failure, perivalvular or myocardial emergence of resistance [173]. Short-course, low-dose

gentamicin combined with vancomycin for MRSA bacteremia entire course must be given parenterally is unknown; there are
and native valve endocarditis was associated with an increased limited data on the use of oral ciprofloxacin in combination
risk of nephrotoxicity [49, 174]; the duration of bacteremia was with oral rifampin primarily in patients with MSSA right-sided
comparable to that observed with vancomycin monotherapy endocarditis [189, 190]. In the absence of additional studies
[172]. The recommendation to treat prosthetic valve MRSA among patients with MRSA, transition from parenteral to oral
endocarditis with vancomycin, gentamicin, and rifampin is therapy should be done cautiously and only in those with un-
based on small retrospective studies of methicillin-resistant co- complicated bacteremia.
agulase-negative staphylococci [175, 176] and the 2005 Ameri- TEE is preferred in adults with MRSA bacteremia because of
can Heart Association (AHA) Infective Endocarditis Guidelines its superiority, compared with TTE, for the detection of vege-
[74]. tations [191–193] and identification of complications, such as
Daptomycin 6 mg/kg/dose IV once daily is an alternative to intracardiac abscess and valvular perforation [194]. In young
vancomycin for adults in the treatment of MRSA bacteremia or children, TTE is likely adequate, given their thin chest wall.
endocarditis. In a randomized trial, it was noninferior to initial Echocardiogram is not routinely recommended for young

low-dose gentamicin plus either vancomycin or an anti- children except in those with congenital heart disease, bacter-
staphylococcal penicillin [49]. Emergence of reduced suscepti- emia of .2–3 days duration, or other clinical findings suggestive
bility to daptomycin was observed in several daptomycin-treated of endocarditis [195]. In patients with MRSA bacteremia and
patients who experienced failure of therapy, most of whom had infected intravascular or prosthetic devices, a higher relapse and
deep-seated infections or left-sided endocarditis. Because it ex- mortality rate has been associated with failure to remove in-
hibits concentration-dependent killing, some experts recom- fected materials [196, 197]. The management of cardiac device-
mend doses of up to 8–10 mg/kg, which appear to be safe, related infections was recently reviewed in the 2010 AHA
although additional studies are needed [177, 178]. Whether this guidelines on cardiovascular implantable electronic device in-
higher dosing strategy prevents the emergence of resistance fections [198]. Patients with endocarditis should be evaluated
[179–181] or improved outcomes is unknown and is under for valve replacement on the basis of clinical and echocardio-
investigation. Although daptomycin should not be used in pa- graphic criteria as per AHA guidelines [74, 199]; data suggest
tients with pneumonia because of inactivation by pulmonary that patients with staphylococcal endocarditis may benefit from
surfactant [182], it can be used in septic pulmonary emboli early surgical intervention [200–204].
[183]. The safety and efficacy of daptomycin in children have
not been established, but it may be effective when given in IV. What is the management of MRSA pneumonia?
combination with other agents in children with disseminated Pneumonia
MRSA infections associated with prolonged bacteremia [184]. 32. For hospitalized patients with severe community-acquired
Doses of 8–10 mg/kg appear to be safe in children, although pneumonia defined by any one of the following: (1) a requirement
additional study is needed [185]. Quinopristin-dalfopristin, for ICU admission, (2) necrotizing or cavitary infiltrates, or (3)
linezolid, TMP-SMX, and telavancin are not recommended empyema, empirical therapy for MRSA is recommended pending
as first-line therapy for MRSA bacteremia. Their role as sputum and/or blood culture results (A-III).
salvage agents for persistent MRSA bacteremia is discussed in 33. For HA-MRSA or CA-MRSA pneumonia, IV vancomycin
Section X. (A-II) or linezolid 600 mg PO/IV twice daily (A-II) or
The duration of therapy for MRSA bacteremia is based on clindamycin 600 mg PO/IV three times daily (B-III) if the
several factors. Patients receiving ,14 days of therapy, including strain is susceptible is recommended for 7-21 days, depending
those with catheter-associated bacteremia, had success rates that on the extent of infection.
were lower than those for patients who received a longer course 34. In patients with MRSA pneumonia complicated by
[186, 187]. For adults, the recommended minimum duration of empyema, antimicrobial therapy against MRSA should be used
therapy for uncomplicated bacteremia is 2 weeks, as defined by: in conjunction with drainage procedures (A-III).
(1) exclusion of endocarditis, (2) no implanted prostheses (eg,
prosthetic valves, cardiac devices, and arthroplasties), (3) follow- Pediatric considerations
up cultures of blood samples drawn 2–4 days after the initial set 35. In children, IV vancomycin is recommended (A-II). If the
that do not grow MRSA, (4) defervescence within 72 h of patient is stable without ongoing bacteremia or intravascular
therapy, and (5) no evidence of metastatic sites of infection [49, infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h (to
188]. If the above criteria are not met, 4–6 weeks of therapy is administer 40 mg/kg/day) can be used as empirical therapy if
recommended for complicated bacteremia depending on the the clindamycin resistance rate is low (eg, ,10%) with
extent of infection; longer durations of therapy may be needed transition to oral therapy if the strain is susceptible (A-II).
in those who are slow to clear their bacteremia. Whether the Linezolid 600 mg PO/IV twice daily for children >12 years of

age and 10 mg/kg/dose every 8 h for children ,12 years of age is V. What is the management of MRSA bone and joint infections?
an alternative (A-II). Osteomyelitis
Evidence Summary 36. Surgical debridement and drainage of associated soft-

Although it remains an uncommon etiology of community- tissue abscesses is the mainstay of therapy and should be
acquired pneumonia (CAP), MRSA has emerged as a cause of performed whenever feasible (A-II).
37. The optimal route of administration of antibiotic therapy
severe CAP [17–21], particularly in the context of a preceding or
has not been established. Parenteral, oral, or initial parenteral
concurrent influenza-like illness, although not exclusively so
therapy followed by oral therapy may be used depending on
[205]. Empirical therapy for MRSA should be considered in
individual patient circumstances (A-III).
patients with severe CAP defined by any one of the following: (1)
38. Antibiotics available for parenteral administration include
a requirement for ICU admission, (2) necrotizing or cavitary IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV once
infiltrates, or (3) empyema. Empirical coverage for MRSA daily (B-II). Some antibiotic options with parenteral and oral
should be discontinued if sputum or blood cultures do not grow

routes of administration include the following: TMP-SMX 4
the organism. mg/kg/dose (TMP component) twice daily in combination
High failure rates have been observed in the treatment of with rifampin 600 mg once daily (B-II), linezolid 600 mg twice
MRSA pneumonia, particularly ventilator-associated pneumo- daily (B-II), clindamycin 600 mg every 8 h (B-III).
nia (VAP) [206–208], which has been attributed to vancomy- 39. Some experts recommend the addition of rifampin
cin’s poor penetration into pulmonary tissue and lung epithelial 600 mg daily or 300–450 mg PO twice daily to the anti-
lining fluid [209]. The addition of rifampin to vancomycin for biotic chosen above (B-III). For patients with concurrent
the treatment of HA-MRSA appears to improve clinical out- bacteremia, rifampin should be added after clearance of
comes, compared with treatment with vancomycin alone, in bacteremia.
40. The optimal duration of therapy for MRSA osteomyelitis
a small, randomized open-label trial, and this deserves addi-
is unknown. A minimum 8-week course is recommended
tional study [210]. Linezolid is an alternative to vancomycin for
(A-II). Some experts suggest an additional 1-3 months (and
the treatment of MRSA pneumonia, achieving greater levels in
possibly longer for chronic infection or if debridement is not
lung epithelial lining fluid than in plasma [211]. Linezolid and
performed) of oral rifampin-based combination therapy
vancomycin were associated with comparable cure rates in 2 with TMP-SMX, doxycycline/minocycline, clindamycin, or
prospective studies involving adult patients with nosocomial a fluoroquinolone, chosen on the basis of susceptibilities
pneumonia [212, 213]; a retrospective pooled subgroup analysis (C-III).
of MRSA cases in these studies found higher cure rates and 41. MRI with gadolinium is the imaging modality of choice,
improved survival in the linezolid arm [214]. A randomized particularly for detection of early osteomyelitis and associated
study of linezolid versus vancomycin for MRSA VAP found no soft-tissue disease (A-II). ESR and/or CRP level may be helpful
significant difference in early microbiologic response rates [215]. to guide response to therapy (B-III).
Thus, it is unclear whether 1 drug is definitively superior to the
Septic Arthritis
other for treatment of MRSA VAP, and additional studies are
ongoing. Linezolid has not been compared with vancomycin for 42. Drainage or debridement of the joint space should always
the treatment of VAP in children. be performed (A-II).
Clindamycin is an alternative to vancomycin for the treat- 43. For septic arthritis, refer to antibiotic choices for
ment of MRSA pneumonia in children [29], and there is limited osteomyelitis (#37 above). A 3-4-week course of therapy is
data regarding its use in adults [205]. Data are insufficient to suggested (A-III).
recommend for or against the use of protein synthesis (eg, toxin) Device-related osteoarticular infections
inhibitors, such as clindamycin or linezolid, as adjunctive
44. For early-onset (,2 months after surgery) or acute
therapy for the treatment of MRSA pneumonia; this topic is
hematogenous prosthetic joint infections involving a stable
discussed further in section VII. Fluoroquinolones may have
implant with short duration (<3 weeks) of symptoms and
activity against some CA-MRSA isolates, but they are not rou- debridement (but device retention), initiate parenteral therapy
tinely recommended, because resistance may emerge with (refer to antibiotic recommendations for osteomyelitis) plus
monotherapy. One small randomized study found that TMP- rifampin 600 mg daily or 300–450 mg PO twice daily for 2
SMX was effective as prophylaxis for MRSA VAP in patients weeks followed by rifampin plus a fluoroquinolone, TMP-
with burns [216], but additional study is needed to determine SMX, a tetracycline or clindamycin for 3 or 6 months for hips
its role in MRSA pneumonia. and knees, respectively (A-II). Prompt debridement with device

removal whenever feasible is recommended for unstable drugs, and greater historical experience, although at increased
implants, late-onset infections, or in those with long duration expense, patient inconvenience, and potential for line-related
(.3 weeks) of symptoms (A-II). complications (eg, infections, line malfunction, and thrombo-
45. For early-onset spinal implant infections (<30 days after phlebitis).
surgery), or implants in an actively infected site, initial Despite concerns about poor bone penetration and relative
parenteral therapy plus rifampin followed by prolonged oral inefficacy in animal models, vancomycin remains the primary
therapy is recommended (B-II). The optimal duration of treatment of MRSA osteomyelitis [218–220]. Failure rates of up
parenteral and oral therapy is unclear; the latter should be to 35%–46% have been reported [221–223], and compared with
continued until spine fusion has occurred (B-II). For late-onset b-lactam therapy, patients with S. aureus osteomyelitis treated
infections (.30 days after implant placement), device removal with vancomycin had a 2-fold higher recurrence rate [224].
whenever feasible is recommended (B-II). These unsatisfactory responses to vancomycin have led some
46. Long-term oral suppressive antibiotics (eg, TMP-SMX, experts to recommend the addition of rifampin because of its
a tetracycline, a fluoroquinolone [which should be given in excellent penetration into bone and biofilm [219]. In animal

conjunction with rifampin due to the potential emergence of models of S. aureus osteomyelitis, therapy with rifampin com-
fluoroquinolone resistance, particularly if adequate surgical bined with a second agent is more effective than is therapy with
debridement is not possible], or clindamycin) with or without the companion agent given alone [120]. There are no controlled
rifampin may be considered in selected cases, particularly if trials of MRSA osteomyelitis, but 2 small trials of MSSA oste-
device removal not possible (B-III). omyelitis suggested higher cure rates were associated with re-
Pediatric considerations ceipt of rifampin combination therapy [73, 225]. Retrospective
studies of rifampin-based regimens for MRSA osteomyelitis
47. For children with acute hematogenous MRSA osteomy- have yielded mixed results, with 1 study indicating cure rates of
elitis and septic arthritis, IV vancomycin is recommended (A- up to 80% [226]; however, 1 study showed no added benefit of
II). If the patient is stable without ongoing bacteremia or rifampin if debridement occurred [227]. For patients with
intravascular infection, clindamycin 10–13 mg/kg/dose IV concurrent bacteremia, rifampin should be added to the treat-
every 6–8 h (to administer 40 mg/kg/day) can be used as ment regimen after clearance of bacteremia. Daptomycin is
empirical therapy if the clindamycin resistance rate is low (eg, a parenteral alternative to vancomycin. In a noncomparative
,10%) with transition to oral therapy if the strain is study involving adults with osteomyelitis treated with dapto-
susceptible (A-II). The exact duration of therapy should be
mycin, clinical improvement was noted in 90%, with better
individualized, but typically a minimum 3–4-week course is
outcomes at 6 mg/kg/day than at lower dosages [228]. Dapto-
recommended for septic arthritis and a 4–6-week course is
mycin may have benefit when added to standard therapy in
recommended for osteomyelitis.
children with refractory invasive MRSA disease if osteomyelitis
48. Alternatives to vancomycin and clindamycin include the
is present [184]. Susceptibility testing must be performed, be-
following: daptomycin 6 mg/kg/day IV once daily (C-III) or
cause daptomycin-nonsusceptible isolates have been described
linezolid 600 mg PO/IV twice daily for children >12 years of
in cases of treatment failure [42, 43, 229–231].
age and 10 mg/kg/dose every 8 h for children ,12 years of age
Oral therapies, administered as either primary or step-down
(C-III).
therapy, appear to be suitable alternatives to prolonged paren-
Evidence Summary teral therapy. In a randomized trial involving adult patients with
MRSA bone and joint infections arise from hematogenous chronic nonvertebral MSSA osteomyelitis, equivalent cure rates
seeding, a contiguous focus of infection, or direct inoculation of 90% were achieved for 8 weeks of oral TMP-SMX (7–8 mg/
from trauma or a medical procedure. Definitive therapy requires kg/day of TMP component) plus rifampin 600 mg once daily
surgical debridement of necrotic bone or the joint space and and a 6-week regimen of IV cloxacillin followed by 2 weeks of
drainage of adjacent abscesses, along with antimicrobial therapy oral therapy [86]; there are no data regarding TMP-SMX plus
[217, 218]. Current treatment strategies are based largely on rifampin involving children with osteomyelitis. In another study
noncomparative case series, case reports, and animal models and of MSSA and MRSA osteomyelitis, similar outcomes were ob-
are extrapolated from those for MSSA infection. The optimal served in those patients who received prolonged parenteral
route of administration (parenteral vs oral vs initial parenteral therapy and those who received oral step-down therapy (.50%
therapy followed by oral therapy) has not been clearly estab- of regimens included rifampin in combination with another
lished; this decision should be based on individual patient cir- agent) following initial parenteral therapy for 2 weeks [221].
cumstances after weighing the pros and cons of each approach. Oral antibiotics that have been used following initial parenteral
Compared with oral therapy, parenteral therapy may offer the therapy for the treatment of osteomyelitis include the following:
potential for better compliance, superior serum levels for certain clindamycin, linezolid, fluoroquinolones, and doxycycline or

minocycline with or without rifampin [221, 222, 226]. Clinda- children, surgical debridement of the hips is recommended,
mycin achieves good bone concentrations and is highly effective whereas arthrocentesis may be adequate for other infected joints
for treatment of non–critically ill children with MRSA osteo- [245]. Although a randomized trial in children with septic ar-
myelitis [34, 232]; there are limited data regarding its use in thritis demonstrated that 10 days of antibiotics was noninferior
adults. Linezolid achieves good concentrations in infected bone; to 30 days of comparable therapy, only 35 episodes of S. aureus
small case series involving adults and children with MRSA os- arthritis, none of which involved MRSA, were treated for
teomyelitis, septic arthritis, or prosthetic joint infections suggest 10 days; in 3 of these cases, therapy was extended to 20 days
that it is effective [233–237]. Weekly monitoring of complete because of inadequate response [246]. Most experts suggest
blood counts is recommended if therapy exceeds 2 weeks; an treating for 3-4 weeks and longer if contiguous osteomyelitis,
ophthalmologic examination should be performed at 1 month noted in up to 30% of children, is present [245]. Clinical re-
after therapy initiations, because optic neuritis may occur sponse should guide the decision to convert from parenteral to
with prolonged treatment [119, 236, 237]. There are limited oral therapy; in one study, switching to oral therapy at 7 days,
data regarding the use of tetracyclines for the treatment of S. compared with switching at 18 days, resulted in similar out-

aureus osteomyelitis [76, 226], and although fluoroquinolones comes [247].
may be effective, they should only be used in combination
with rifampin because of the potential for the development of
VI. What is the management of MRSA infections of the CNS?
resistance. Meningitis
The optimal duration of therapy for osteomyelitis is un-
known. Antibiotic therapy for 8 weeks, compared with shorter 49. IV vancomycin for 2 weeks is recommended (B-II). Some
durations, have been associated with improved outcomes in experts recommend the addition of rifampin 600 mg daily or
those with S. aureus osteomyelitis [226, 238], whereas undrained 300–450 mg twice daily (B-III).
abscesses and inadequate debridement are associated with re- 50. Alternatives include the following: linezolid 600 mg PO/IV
lapse rates of 30%–60%, which emphasizes the importance of twice daily (B-II) or TMP-SMX 5 mg/kg/dose IV every 8–12 h
surgical therapy [227, 239]. Some experts suggest oral con- (C-III).
solidative treatment after a course of parenteral therapy for an 51. For CNS shunt infection, shunt removal is recommended
and it should not be replaced until CSF cultures are repeatedly
additional 1–3 months and possibly longer for treatment of
negative (A-II).
chronic infection, if debridement is not performed or if in-
flammatory markers, such as ESR and CRP level, remain ele- Brain abscess, subdural empyema, spinal epidural abscess
vated [222]. In a study of vertebral osteomyelitis, this approach
52. Neurosurgical evaluation for incision and drainage is
yielded an 83% cure rate [226].
recommended (A-II).
In a randomized study of staphylococcal prosthetic hip and
53. IV vancomycin for 4–6 weeks is recommended (B-II).
knee joint infections (which included no infections due to
Some experts recommend the addition of rifampin 600 mg
MRSA) in patients with early-onset (,2 months after surgery)
daily or 300–450 mg twice daily (B-III).
infections, stable implants, and , 3 weeks of symptoms, 3–6
54. Alternatives include the following: linezolid 600 mg PO/IV
months of rifampin-based combination therapy plus surgical
twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h
debridement without device removal was found to be effective
(C-III).
[72]. Rifampin dosing in studies of staphylococcal prosthetic
joint infections is variable, ranging from 600 mg daily to 300– Septic Thrombosis of Cavernous or Dural Venous Sinus
450 mg twice daily [72, 240, 241]. Debridement and device re- 55. Surgical evaluation for incision and drainage of
moval using a 2-stage exchange arthroplasty is recommended contiguous sites of infection or abscess is recommended
for late-onset infections, unstable implants, or a prolonged whenever possible (A-II). The role of anticoagulation is
duration (.3 weeks) of symptoms [242]. For early-onset spinal controversial.
implant infections (<30 days of implant placement), 6 weeks of 56. IV vancomycin for 4–6 weeks is recommended (B-II).
parenteral therapy followed by prolonged oral suppressive Some experts recommend the addition of rifampin 600 mg
therapy until spine fusion resulted in improved outcomes [243]. daily or 300–450 mg twice daily (B-III).
For late-onset infections (.30 days after implant placement), 57. Alternatives include the following: linezolid 600 mg PO/IV
implant removal was critical to success. For ankle fractures, 6 twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h
weeks of therapy after hardware removal appears to be effective (C-III).
[244].
Drainage and debridement of the intra-articular cavity is es-
sential for effective treatment of septic arthritis [217]. In 58. IV vancomycin is recommended (A-II).

Evidence Summary daptomycin [269] for the treatment of MRSA CNS infections,
CNS infections caused by MRSA occur as a complication of but additional research is needed to define their role in the
a neurosurgical procedure, in association with a contiguous management of such infections.
focus of infection, or hematogenously as a complication of For meningitis in association with a CNS shunt, shunt re-
bacteremia or infective endocarditis. Treatment is difficult be- moval with placement of an external ventricular drain is critical
cause of the critical location of these infections and the blood to therapy [270–273]. CSF cultures should be repeatedly
brain barrier, which limits penetration of systemically admin- negative prior to placement of a new shunt [273]. Retention of
istered antibiotics to the site of infection. Thus, surgical drainage infected shunts is associated with a high failure rate despite
of focal abscesses and removal of any foreign body, such as an administration of both intraventricular and systemic antibiotics
infected shunt, should be performed whenever possible. [274]. Once the shunt has been removed, systemic antimicrobial
Resistance to multiple antibiotics and the inability of many therapy is usually effective. Although there are very limited
antibiotics to achieve therapeutic concentrations in CSF severely data to guide use, intraventricular vancomycin [248, 275] or
limit the choices for antimicrobial therapy of MRSA CNS in- daptomycin [276] may be considered in patients who have

fections. CSF penetration of vancomycin is poor, approximately ventricular access or who do not respond to systemic antimi-
1% and 5% for uninflamed and inflamed meninges, respectively, crobial therapy.
with maximum CSF concentrations of 2–6 lg/mL [248–250]. Considerable controversy surrounds the use of systemic an-
Linezolid has good CSF penetration, as high as 66%, with CSF ticoagulation for septic cavernous or dural sinus thromboses
peak and trough concentrations of 7–10 lg/mL and 2.5–6.0 lg/ because of the risk of intracranial hemorrhage [277, 278]. If
mL, respectively [251–253]. CSF penetration of TMP-SMX is anticoagulation is used, heparin should be used, because it is
similar for uninflamed and inflamed meninges, 13%–53% for reversible, and imaging should be performed to exclude lesions
TMP and 17%–63% for SMX; CSF concentrations are 1.9–5.7 predisposing to hemorrhage.
lg/mL for TMP and 20–63 lg/mL for SMX after a 10 mg/kg/day
dosage and a 50 mg/kg/day dosage, respectively [254, 255]. CSF VII. What is the role of adjunctive therapies for the treatment of
penetration of rifampin is 22% and is similar for inflamed and MRSA infections?
noninflamed meninges, and bactericidal concentrations are
achievable in CSF. A 600-mg dose in adults without inflamed 59. Protein synthesis inhibitors (eg, clindamycin and line-
zolid) and IVIG are not routinely recommended as adjunctive
meninges produced CSF concentrations of 0.57–1.24 lg/mL
therapy for the management of invasive MRSA disease (A-III).
[70]. In a rabbit meningitis model, CSF penetration of dapto-
Some experts may consider these agents in selected scenarios
mycin was 5%–6% with concentrations of 3.2–4.0 lg/mL; values
(eg, necrotizing pneumonia or severe sepsis) (C-III).
were halved for uninflamed meninges [256, 257].
There are no prospective randomized trials on the treatment Evidence Summary
of MRSA infections of the CNS. Vancomycin has been the drug Specific recommendations regarding combination antibiotic
of choice, but outcomes have been very poor when it has been therapy for individual disease entities are discussed in the re-
used as monotherapy [258, 259]. Because of the limited pene- spective sections of the text. This section will focus on the use of
tration of vancomycin across even inflamed meninges, con- protein synthesis inhibitors and IVIG as adjunctive therapy.
centrations in CSF (and presumably other CNS sites as well) Data are insufficient to recommend for or against the use of
may be marginal when the drug is administered intravenously at protein synthesis inhibitors as adjunctive therapy of invasive
standard dosages. Because it achieves bactericidal concentrations disease caused by MRSA. Limited in vitro data suggest that
in CSF, some experts recommend rifampin in combination with clindamycin and linezolid inhibit production of staphylococcal
vancomycin for meningitis and other CNS infections, despite toxic shock syndrome toxin type 1 and PVL [279–281] and
a paucity of clinical data demonstrating benefit of the combi- that linezolid suppresses alpha- and beta-hemolysins, staphylo-
nation [120, 260–262]. High-dose, continuous infusion of coccal enterotoxin A and B, and protein A [282]. However,
vancomycin may be considered in patients not responding to clindamycin or linezolid in combination with vancomycin can
standard dosing methods. CSF penetration was increased and be antagonistic in vitro [283–286], and vancomycin alone was
concentrations were almost doubled, compared with standard more effective than vancomycin plus linezolid in a rabbit en-
dosing, when vancomycin was administered as a 15 mg/kg docarditis model [287]. Existing clinical data are limited to case
loading dose, followed by continuous infusion of 50–60 mg/kg/ reports for patients with staphylococcal toxic shock syndrome
day for patients with normal renal function [105]. The regimen [281] and necrotizing/cavitary pneumonia [205, 288], and ad-
was well tolerated, although nephrotoxicity has been associated ditional studies are needed.
with high doses [263]. Several case reports describe the suc- The role of IVIG in the management of invasive MRSA dis-
cessful use of linezolid [264–267], TMP-SMX [255, 268], and ease is even less clear. IVIG neutralizes staphylococcal exotoxins,

including PVL [289], although staphylococcal superantigens Pediatric considerations
and exotoxins are less efficiently inhibited by IVIG than by 67. Data are limited to guide vancomycin dosing in children.
streptococcal superantigens [290]. Children with invasive dis- IV vancomycin 15 mg/kg/dose every 6 h is recommended in
ease have higher concentrations of antibody to PVL than do children with serious or invasive disease (B-III).
those with SSTIs [291]; it is unclear whether antibody to PVL in 68. The efficacy and safety of targeting trough concentrations
IVIG offers additional benefit. In fact, one study suggests that of 15–20 lg/mL in children requires additional study
antibody to PVL may be detrimental [292]. Meta-analyses on but should be considered in those with serious infections,
the use of IVIG in sepsis and septic shock have indicated such as bacteremia, infective endocarditis, osteomyelitis,
a mortality benefit, but no benefit was observed when only high- meningitis, pneumonia, and severe SSTI (ie, necrotizing
quality trials were included in the analyses [293–296]. Given the fasciitis) (B-III).
available data, IVIG is not recommended in the management of
MRSA disease, although its use may be considered in children Evidence Summary
with severe MRSA sepsis [297]. Vancomycin doses of 15–20 mg/kg/day every 8–12 h are rec-

ommended for adult patients on the basis of actual body weight
VIII. What are the recommendations for vancomycin dosing and and are adjusted for the patient’s estimated creatinine clearance,
monitoring? not to exceed 2 g per dose. Weight-based dosing is particularly
These recommendations are based on a consensus statement of important in obese patients, who are likely to be underdosed
the American Society of Health-System Pharmacists, the IDSA, when conventional dosing strategies of 1 g every 12 h are used.
and the Society of Infectious Diseases Pharmacists on guidelines Some experts suggest vancomycin loading doses for serious
for vancomycin dosing [3,4]. suspected or documented MRSA infections (sepsis, meningitis,
Adults pneumonia, or endocarditis) to enable early achievement of
60. IV vancomycin 15–20 mg/kg/dose (actual body weight) target trough concentrations, although clinical data are lacking
every 8–12 h, not to exceed 2 g per dose, is recommended in [298, 299]. A vancomycin loading dose of 25 mg/kg was found
patients with normal renal function (B-III). to be safe in a small study [300]. Because of the lack of a clear
61. In seriously ill patients (eg, those with sepsis, meningitis, benefit over intermittent dosing, and because time .MIC is not
pneumonia, or infective endocarditis) with suspected MRSA the primary predictor of efficacy [301–303], continuous in-
infection, a loading dose of 25–30 mg/kg (actual body weight) fusion vancomycin is not recommended.
may be considered. (Given the risk of red man syndrome and The pharmacodynamic parameter that best predicts efficacy
possible anaphylaxis associated with large doses of vancomycin, of vancomycin is the ratio of the area under the curve (AUC) to
one should consider prolonging the infusion time to 2 h and the MIC (AUC/MIC) [304–306]. A single study involving pa-
use of an antihistamine prior to administration of the loading tients with S. aureus lower respiratory tract infections reported
dose.) (C-III). that an AUC/MIC >400, compared with an AUC/MIC ,400,
62. Trough vancomycin concentrations are the most accurate was associated with improved clinical response and microbio-
and practical method to guide vancomycin dosing (B-II). logic eradication [307]. In a study involving patients with MRSA
Serum trough concentrations should be obtained at steady health care–associated pneumonia, mean trough vancomycin
state conditions, prior to the fourth or fifth dose. Monitoring levels of 9.4 lg/mL and 20.4 lg/mL correlated with a mean AUC
of peak vancomycin concentrations is not recommended (6 standard deviation) of 318 6 111 lgh/mL and 418 6 152
(B-II). lgh/mL, respectively, although no association between trough
63. For serious infections, such as bacteremia, infective concentrations and clinical response was observed [308]. Ad-
endocarditis, osteomyelitis, meningitis, pneumonia, and severe ditional studies are needed to verify the target AUC/MIC >400
SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin trough but, on the basis of currently available data, vancomycin trough
concentrations of 15–20 lg/mL are recommended (B-II). concentrations of 15–20 lg/mL are needed to achieve this target
64. For most patients with SSTI who have normal renal if the MIC of the organism is <1 lg/mL. The probability of
function and are not obese, traditional doses of 1 g every 12 h achieving target AUC/MIC of .400 is 100% for vancomycin
are adequate and trough monitoring is not required (B-II). MIC of 0.5 lg/mL and 0% for MIC value of 2 lg/mL even if
65. Trough vancomycin monitoring is recommended for aggressive dosing strategies are used [298]. In patients with
serious infections and patients who are morbidly obese, have normal renal function, up to 3–4 g/day of vancomycin may be
renal dysfunction (including those receiving dialysis), or have required to attain target AUC/MIC.
fluctuating volumes of distribution (A-II). Measuring trough serum concentrations, which are predictive
66. Continuous infusion vancomycin regimens are not of AUC/MIC, is the most practical means of monitoring van-
recommended (A-II). comycin. Vancomycin trough concentrations ,10 lg/mL have

been associated with treatment failures, perhaps attributable to Evidence Summary
variable penetration into tissue compartments and selection of The emergence of hVISA, VISA and VRSA poses an additional
vancomycin-heteroresistant S. aureus (hVISA) [309]. Clinical challenge to use of this drug. Although these strains are relatively
data to support higher target troughs are limited. A trough >15 uncommon, they are associated with vancomycin treatment
lg/mL has not clearly been associated with improved outcomes failures and poor outcomes [235, 309, 320, 321]. As a result,
[310] [311], duration of bacteremia, or mortality [308, 312]. MIC breakpoints were lowered by the CLSI in 2006 from <4 lg/
However, to optimize vancomycin pharmacodynamics, improve mL to <2 lg/mL for susceptible strains, with MICs of 4–8 lg/
tissue penetration, and minimize selection of resistant strains, mL and >16 lg/mL now indicating intermediate and resistant
the Panel suggests targeting higher trough concentrations strains, respectively. Detection of these strains—in particular,
for serious infections due to MRSA. For less serious infections, hVISA, in which a small, resistant subpopulation of cells is
including most SSTIs, traditional dosing in the adult present—remains a limitation of susceptibility testing methods
patient with normal renal function and weight is likely to be [322–324]. The current ‘‘gold standard’’ for hVISA detection is
adequate on the basis of excellent clinical response rates population analysis profile (PAP) divided by the AUC; however,

without a more aggressive dosing strategy [50, 136, 138, this method is labor-intensive and impractical for the clinical
313, 314]. Higher vancomycin doses and trough concentrations laboratory [325, 326]. Several less laborious tests, including the
may be associated with increased nephrotoxicity [263, 311, macrodilution Etest, Etest glycopeptide resistance detection, and
315, 316] and high-frequency hearing loss in older patients Mueller-Hinton agar with 5 mg/L teicoplanin, are more sensitive
[317]. Such investigations are limited by small sample and specific for hVISA detection than are other methods [322,
sizes, retrospective design, and co-administration of other 327–329], although the optimal assay most predictive of out-
nephrotoxic agents. Clearly, additional prospective studies are comes is unclear. Given current limitations, testing for hVISA is
needed, particularly because higher dosing strategies are not routinely recommended. For patients with an isolate with
implemented. a vancomycin MIC of 2 lg/mL, particularly those patients with
There are limited data to guide vancomycin dosing in chil- limited or no clinical response to vancomycin therapy, an al-
dren with MRSA. Pharmacodynamic data suggest that higher ternate method, such as Etest, should be performed to improve
dosages (60 mg/kg/day) are required to achieve AUC/MIC .400 detection of VISA [330].
for isolates with a vancomycin MIC <1 lg/mL [318], but In recent years, several centers have observed an ‘‘MIC creep’’
additional research is needed. A loading dose of 20–25 mg/kg among MRSA isolates characterized as susceptible by CLSI cri-
may be considered in seriously ill children. The efficacy teria [331, 332], with the principle concern being the gradual loss
and safety of targeting trough concentrations of 15–20 lg/mL of vancomycin activity, because clinical failures appear to be
for invasive infections in children have not been studied more common among those with MIC values of 2 lg/mL than
but should be considered in serious infections, such as bacter- among those with MIC values ,2 lg/mL [95, 310, 311, 333, 334].
emia, endocarditis, osteomyelitis, meningitis, pneumonia, and To date, no alternate regimens have been clearly shown to result
severe SSTI (ie, necrotizing fasciitis). Vancomycin nephrotoxi- in better clinical outcomes in those patients with isolates with
city is more common with concomitant aminoglycoside use vancomycin MICs of 2 lg/mL. In addition, data regarding
[319]. the presence or absence of ‘‘MIC creep’’ is conflicting and has
not been confirmed by other groups [335–338]. In a large
IX. How should results of vancomycin susceptibility testing be multicenter study, the frequency of MRSA isolates with an MIC
used to guide therapy?
.1 lg/mL as determined by reference broth microdilution
69. For isolates with a vancomycin MIC <2 (eg, susceptible ranged from 1.6%–3.7% and was primarily attributable to clonal
according to CLSI breakpoints), the patient’s clinical response dissemination of a USA100 strain with reduced susceptibility to
should determine the continued use of vancomycin, indepen- vancomycin [338].
dent of the MIC (A-III). Interpretation of these data is further complicated by limi-
tations in currently available susceptibility testing methods and
i. If the patient has had a clinical and microbiologic response the considerable variability in MIC results, depending on the
to vancomycin, then it may be continued with close follow-up
method used. One challenge is that acceptable variability for
ii. If the patient has not had a clinical or microbiologic
MIC methods is 6 1 doubling dilution [339], which makes it
response to vancomycin despite adequate debridement and
difficult to distinguish between an MIC of 1 versus 2 lg/mL.
removal of other foci of infection, an alternative to vancomycin
Etest, MicroScan, and BD-Phoenix report MIC values that are
is recommended regardless of MIC.
higher than those reported by reference broth microdilution,
70. For isolates with a vancomycin MIC .2 lg/mL (eg, VISA overcalling susceptible strains as intermediate in some cases,
or VRSA), an alternative to vancomycin should be used (A-III). whereas the Sensititre and Vitek 2 systems tend to undercall

resistance [330]. In one study, up to 98% of MICs were reported cure or sterilizing blood cultures, which poses a challenge to the
as 1.5 or 2 lg/mL by Etest, but when CLSI broth dilution management of such infections.
method was used, only 3% of isolates were found to have The point at which the patient should be considered to have
a vancomycin MIC of 2 lg/mL [340]. Because Etest and other experienced treatment failure and alternative therapy sought is
methods have a tendency to report MIC results that are higher a complex issue. Because the median time to clearance of MRSA
than those reported by reference broth microdilution, it is un- bacteremia is 7–9 days [49, 172], most experts agree that per-
known whether the ‘‘MIC creep’’ represents a true phenome- sistent bacteremia at or around day 7 of therapy should prompt
non, whether it is a technical artifact that depends on the test an assessment to determine whether a change in therapy is in-
method used, or whether it applies to a few institutions as a re- dicated. Several factors should be considered, including the
sult of clonal spread. The existence or extent of ‘‘MIC creep’’ for following: (1) the patient’s overall clinical response; (2) vanco-
pediatric MRSA isolates is not well characterized. In one mycin trough serum concentrations; (3) results of susceptibility
children’s hospital, an increase in the vancomycin MIC for S. testing; and (4) the presence of and ability to remove other foci
aureus isolates was observed with Etest but not with broth mi- of infection. The decision to modify therapy and the time frame

crodilution testing [341]. Because current susceptibility testing at which this occurs may vary depending on the clinical scenario.
methods are unable to reliably distinguish MICs of 1 lg/mL Although modification of therapy should generally be consid-
from MICs of 2 lg/mL, the Panel recommends evaluation of the ered if the patient is persistently bacteremic after 1 week of
patient’s clinical and microbiologic response along with MIC vancomycin therapy, the threshold to change therapy may be
results when making decisions regarding therapy. earlier if the patient’s clinical condition is worsening despite
adequate debridement and removal of other foci of infection or
X. What is the management of persistent MRSA bacteremia and if the vancomycin MIC is 2 lg/mL, particularly in septic or
vancomycin treatment failures in adult patients? critically ill patients. On the other hand, no immediate change in
therapy may be indicated if the patient is clinically responding
71. A search for and removal of other foci of infection, and the vancomycin MIC is ,2 lg/mL; in many cases, the
drainage or surgical debridement is recommended (A-III).
bloodstream will clear with continued vancomycin therapy.
72. High-dose daptomycin (10 mg/kg/ day), if the isolate is
In general, when constructing an alternate regimen in the
susceptible, in combination with another agent (e.g. gentami-
setting of vancomycin treatment failure in adult patients, the
cin 1 mg/kg IV every 8 h, rifampin 600 mg PO/IV daily or
Panel recommends a change in therapy rather than the addition
300-450 mg PO/IV twice daily, linezolid 600 mg PO/IV BID,
of other agents (eg, rifampin and gentamicin) to vancomycin.
TMP-SMX 5 mg/kg IV twice daily, or a beta-lactam antibiotic)
Among the possible choices, daptomycin has the most rapidly
should be considered (B-III).
bactericidal activity [343, 344], although the use of daptomycin
73. If reduced susceptibility to vancomycin and daptomycin are to treat patients who have not responded to vancomycin re-
present, options may include the following: quinupristin- quires special consideration. Isolates with vancomycin MICs >2
dalfopristin 7.5 mg/kg/dose IV every 8 h, TMP-SMX 5 mg/kg/ lg/mL may have daptomycin MICs in the nonsusceptible range
dose IV twice daily, linezolid 600 mg PO/IV twice daily, or (.1 lg/mL) and in vitro exposure to vancomycin may select for
telavancin 10 mg/kg/dose IV once daily (C-III). These options higher daptomycin MICs [47, 48, 179, 345–347]. Persistent
may be given as a single agent or in combination with other bacteremia and clinical failures with daptomycin have been as-
antibiotics. sociated with daptomycin MICs .1 lg/mL [49, 348]. The 10-
mg/kg dose, which appears to be safe [178], is recommended on
Evidence Summary the basis of limited in vitro evidence that suggests that higher
Clinical or microbiological failures occur in a substantial pro- doses may suppress the emergence of resistance [179–181] and
portion of invasive MRSA infections treated with vancomycin. some clinical data that indicates the potential efficacy of dap-
Persistent bacteremia and relapse are common among patients tomycin at 10 mg/kg/day in clearing complicated MRSA bac-
with infective endocarditis [171] and account for 17% of the teremia due to strains with a daptomycin MIC of 2 lg/mL [349].
vancomycin failures in a randomized trial [49]. Persistent bac- Although there are no clinical data, and although additional
teremia is associated with worse clinical outcomes [171, 342]. study is needed, some experts suggest the use of daptomycin in
Vancomycin treatment failures have been attributed to the combination with another agent, such as gentamicin adminis-
drug’s slow bactericidal activity, emergence of strains with re- tered at a dosage of 1 mg/kg every 8 h, rifampin, or both drugs if
duced susceptibility to vancomycin, possible enhanced virulence the strain is susceptible to both [96, 181, 350, 351]. Synergy has
of CA-MRSA, and inadequate debridement or retained pros- been described in vitro and in animal models between dapto-
thetic device. Yet, at this time, no alternative agent or regimen mycin and gentamicin [96, 181, 350–352], daptomycin and ri-
has proven to be superior to vancomycin in achieving clinical fampin [351, 353], and among all 3 drugs [351], although one

study suggests that the combination of daptomycin and rifam- sites in full-term infants, IV vancomycin or clindamycin is
pin may be antagonistic [354]. Once-daily gentamicin at 5 mg/ recommended, at least initially, until bacteremia is excluded
kg may be an alternative to traditional dosing and has a lower (A-II).
risk of nephrotoxicity [355].
Neonatal MRSA sepsis
There are even less data to guide the management of patients
with isolates that are nonsusceptible to both vancomycin and 76. IV vancomycin is recommended, dosing as outlined in
daptomycin and who are experiencing failure of therapy [324]. the Red Book (A-II).
Quinupristin-dalfopristin has been used successfully as salvage 77. Clindamycin and linezolid are alternatives for non-
therapy in patients with vancomycin treatment failure [65], al- endovascular infections (B-II).
though response rates were lower for patients with endocarditis
Evidence Summary
and bacteremia of unknown source [64]. TMP-SMX is bacte- For neonates with localized pustulosis, clinical experience sug-
ricidal in vitro, it but was inferior to vancomycin for the treat- gests that topical mupirocin alone may be effective, although
ment of S. aureus infections, although all treatment failures

parenteral antibiotic therapy is recommended for more-exten-
occurred among those with MSSA infection, whereas all patients sive disease. Lumbar puncture is not necessary in a full-term
with MRSA infection were cured [90]. Thymidine release from infant ,30 days of age with localized pustulosis with no signs or
damaged host cells and bacteria may limit the efficacy of folate symptoms of sepsis [368]. Vancomycin is the primary treatment
antagonists, so caution should be exercised when using TMP- for serious MRSA infections in the neonatal period. There are
SMX for the treatment of serious S. aureus infections [356]. limited data on the potential benefit of combination therapy
Some experts suggest the addition of gentamicin or rifampin if with rifampin, gentamicin, or daptomycin in neonatal staphy-
TMP-SMX is used in salvage therapy. The combination of lococcal sepsis [184, 369]; the decision to use combination
daptomycin and trimethoprim-sulfamethoxazole had rapid therapy should be individualized. Experience with clindamycin
bactericidal activity compared to daptomycin alone for a dap- and linezolid for serious neonatal MRSA infections is limited,
tomycin non-susceptible strain in an in vitro study [371]. but these drugs may be considered for treatment of patients with
Linezolid has been used with some success in several series either susceptible isolates who have nonendovascular infections [29,
alone or in combination with other agents (eg, rifampin, fusidic 370]. TMP-SMX is not recommended during the immediate
acid, gentamicin, amikacin, and carbapenem), but outcomes for neonatal period because of increased risk of kernicterus.
patients with left-sided endocarditis have been poor [235, 357–
360]. Of note, rifampin may decrease linezolid levels when given
RESEARCH GAPS
in combination via an unclear mechanism [361–363]. There is
one case report of persistent MRSA bacteremia in a patient with The initial step in developing a rational clinical research agenda
tricuspid valve endocarditis that was successfully treated with is the identification of gaps in information. The process of
telavancin [364]. The combination of vancomycin plus a b- guideline development, as practiced by the IDSA, serves as
lactam has been shown to be synergistic in vitro and in vivo for a natural means by which such gaps are identified. Thus, the
VISA and VRSA [365, 366], although additional clinical studies guidelines identify important clinical questions and identify the
are needed. More recently, similar observations have been seen quality of evidence supporting those recommendations. Clinical
with daptomycin in combination with a b-lactam for treatment questions identified by guideline authors and members of the
of infection due to daptomycin nonsusceptible strains [367]. IDSA Research Committee that could inform a MRSA research
Hopefully, newer compounds that are under development for agenda are included below.
the treatment of MRSA infections will provide more effective
alternatives in the future. Bacteremia and Endocarditis
Data are insufficient to guide the management of persistent What is the role of echocardiography, and does it improve
MRSA bacteremia in children, and the decision regarding use of outcome? Should it be performed routinely in all patients with
alternate or combination therapy should be individualized. S. aureus bacteremia or only in certain subsets? Should the
preferred modality be TEE or is a transthoracic examination
XI. What is the management of MRSA infections in neonates? sufficient in certain cases?
Neonatal pustulosis How extensive should the work-up be to identify occult foci
74. For mild cases with localized disease, topical treatment of metastatic infection? Is a symptoms-and-signs based ap-
with mupirocin may be adequate in full-term neonates and proach sufficient, or is there a minimal panel of studies that
young infants (A-III). should be performed?
75. For localized disease in a premature or very low- What is the optimal initial therapy? Should vancomycin
birthweight infant or more-extensive disease involving multiple be the first drug of choice for empirical therapy? Should the

patient also receive a b-lactam antibiotic to cover for methicil- What is the optimal management of abscesses? Is there any
lin-susceptible strains pending susceptibility test data? additional benefit of antibiotics, particularly with regard to
What is the optimal therapy once susceptibility test results impact on recurrent infections and household transmission?
are available? What is the optimal therapy for patients with What is optimal management for recurrent SSTIs? What
metastatic foci of infection? Is there any role for combination is the pathogenesis of recurrent SSTIs? What is the nature of the
therapy? interplay between the pathogen, host colonization, and the en-
What regimens should be used in treating persistent or vironment? Is decolonization effective in preventing recurrent
relapsing infection? What duration of persisting bacteremia SSTI? If so, what are the appropriate regimens? What specific
signals a need for a change in antibiotic therapy? What alter- environmental hygiene measures should be taken to prevent
native antibiotic regimens should be used? What is the role of recurrent SSTI and household transmission?
combination therapy? What susceptibility test methods and
breakpoint best predict treatment failure, particularly for van- PERFORMANCE MEASURES
comycin? Should strains with a vancomycin MIC of 2 lg/mL

1. The management of all MRSA infections should include
be considered to be nonsusceptible, and if so, what test should
identification, elimination and/or debridement of the primary
be used to determine MIC? Does infection by so-called hVISA
source and other sites of infection when possible (eg, drainage
strains predict treatment failure, and if so, what are the optimal
of abscesses, removal of central venous catheters, and de-
tests for detecting these strains?
bridement of osteomyelitis).
What is the optimal duration of therapy? Is rapid clear-
2. In patients with MRSA bacteremia, follow-up blood
ance of bacteremia an indicator that an abbreviated course of
cultures 2–4 days after initial positive cultures and as needed
antibiotic therapy is sufficient? Are there subsets of patients for thereafter are recommended to document clearance of
whom shorter courses of therapy (ie, less than the generally bacteremia.
accepted minimum of 14 days) would be effective? What is 3. To optimize serum trough concentrations in adult
the role of biological markers (eg, C-reactive protein or pro- patients, vancomycin should be dosed according to actual
calcitonin) in determining duration of therapy? What is the body weight (15–20 mg/kg/dose every 8–12 h), not to exceed 2
optimal duration of therapy for patients with metastatic foci of g per dose. Trough monitoring is recommended to achieve
infection? target concentrations of 15–20 lg/mL in patients with serious
MRSA infections and to ensure target concentrations in those
Osteomyelitis who are morbidly obese, have renal dysfunction, or have
What is the optimal therapy? What is the importance of fluctuating volumes of distribution. The efficacy and safety of
bactericidal therapy and antimicrobial bone penetration in the targeting higher trough concentrations in children requires
management of osteomeylitis? What is the efficacy of oral versus additional study but should be considered in those with severe
parenteral therapy? Is oral step-down therapy an alternative to sepsis or persistent bacteremia.
prolonged parenteral therapy? Is there any benefit of targeting 4. When an alternative to vancomycin is being considered for
higher vancomycin troughs in osteomyelitis? What are alter- use, in vitro susceptibility should be confirmed and docu-
natives to vancomycin for the management of osteomyelitis mented in the medical record.
caused by MRSA strains with elevated vancomycin MICs? What 5. For MSSA infections, a b-lactam antibiotic is the drug of
is the role of rifampin combination therapy? Does early surgical choice in the absence of allergy.
intervention improve outcome?
Acknowledgments
What is the optimal management of hardware-associated The Expert Panel wishes to express its gratitude to Drs. Gordon Archer,
infections? Frank Lowy, and Brad Spellberg for their thoughtful reviews of earlier drafts
What is the optimal duration of therapy? How best should of the guideline. The Expert Panel also recognizes the following for their
important contributions in identifying critical gaps where funding of re-
laboratory markers of inflammation (ESR and CRP level) be
search is needed to advance clinical treatment and care: William Burman,
used to guide therapy? David M. Margolis, and Louis B. Rice (IDSA Research Committee), Stanley
C. Deresinski (IDSA SPGC), and Padma Natarajan (IDSA staff). The
findings and conclusions of this report are those of the authors and do not
SSTI
necessarily represent the official position of the Centers for Disease Control
What is the optimal management of nonpurulent cellulitis? and Prevention.
What is the microbiology of nonpurulent cellulitis (eg, cellulitis It is important to realize that guidelines cannot always account for
with no purulent drainage or exudate and no associated abscess) individual variation among patients. They are not intended to supplant
physician judgment with respect to particular patients or special clinical
in the era of CA-MRSA? Is initial empirical coverage for MRSA situations. The IDSA considers adherence to these guidelines to be vol-
necessary? untary, with the ultimate determination regarding their application to be

made by the physician in the light of each patient’s individual circum- 11. Moran GJ, Krishnadasan A, Gorwitz RJ, et al Methicillin-resistant S.
stances. aureus infections among patients in the emergency department. N
Financial support. IDSA. Engl J Med 2006; 355:666–74.
Potential conflicts of interest. H.F.C. has received honoraria and re- 12. Lee TC, Carrick MM, Scott BG, et al Incidence and clinical charac-
search grants and has served as a consultant to Cubist, Ortho-McNeil, teristics of methicillin-resistant Staphylococcus aureus necrotizing
Pfizer, Theravance, and Targanta. S. E. C. has received honoraria from fasciitis in a large urban hospital. Am J Surg 2007; 194:809–12;
Forest and RibX, has served as a consultant for Merck and has received discussion, 12–13.
research support from Astellas, Cubist and AdvanDx. R.D. has received 13. Pannaraj PS, Hulten KG, Gonzalez BE, et al Infective pyomyositis and
research funding from Pfizer, Clorox, Sanofi Pasteur, Sage, and GeneOhm. myositis in children in the era of community-acquired, methicillin-
S.L.K. has received grant funding from Pfizer, has served as MRSA Lead- resistant Staphylococcus aureus infection. Clin Infect Dis 2006; 43:953–60.
ership Advisor to Pfizer, and is participating in a pediatric daptomycin 14. Miller LG, Perdreau-Remington F, Rieg G, et al Necrotizing fasciitis
study. A.W.K. has received honoraria and grants from Cubist Pharma- caused by community-associated methicillin-resistant Staphylococcus
ceuticals, Merck, Wyeth, and Pfizer and has served as a consultant for aureus in Los Angeles. N Engl J Med 2005; 352:1445–53.
Cubist Pharmaceuticals, Theravance, Astellas, Pfizer, Merck, and Ortho- 15. Wright CT, Stocks RM, Armstrong DL, et al Pediatric mediastinitis as
McNeil and has owned stock from Cubist Pharmaceutical, Pfizer, and a complication of methicillin-resistant Staphylococcus aureus retro-
Johnson and Johnson. D.P.L. has received research support from Cubist, pharyngeal abscess. Arch Otolaryngol Head Neck Surg 2008;
Johnson & Johnson, and Theravance and has served as a speaker for Cubist.

134:408–13.
B.E.M. has served as a consultant and received research support from 16. Gonzalez BE, Teruya J, Mahoney DH Jr., et al Venous thrombosis
Johnson & Johnson, Astellas, Pfizer, Cubist, Theravance, Targanta, Sanofi- associated with staphylococcal osteomyelitis in children. Pediatrics
Aventis, Vicuron Pharmaceuticals, and Wyeth-Ayerst. M.R. has received 2006; 117:1673–9.
grants and or has served as a consultant speaker for the Pfizer, Cubist, 17. Francis JS, Doherty MC, Lopatin U, et al Severe community-onset
Theravance/Astellas, Targanta, and Johnson & Johnson. D.A.T. has served pneumonia in healthy adults caused by methicillin-resistant Staphy-
on the advisory board to Pfizer, Ortho-McNeil, Astellas, Schering-Plough, lococcus aureus carrying the Panton-Valentine leukocidin genes. Clin
and Replidyne. All other authors: no conflicts. Infect Dis 2005; 40:100–7.
18. Hageman JC, Uyeki TM, Francis JS, et al Severe community-acquired
pneumonia due to Staphylococcus aureus, 2003-04 influenza season.
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Manejo de Estafilococo Meticilinoresistente

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IDSA GUIDELINES

Clinical Practice Guidelines by the Infectious Diseases

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Manifestation Treatment Adult dose Pediatric dose Classa Comment

MRSA Treatment Guidelines

CID 2011:52 (1 February)

CID 2011:52 (1 February)

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Bone and joint infections

MRSA Treatment Guidelines

CID 2011:52 (1 February)

CID 2011:52 (1 February)

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Evidence Summary 36. Surgical debridement and drainage of associated soft-

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