No está claro cuán grande es el papel de los antibióticos https://antibioticos-wiki.es en las relaciones competitivas entre los microorganismos en condiciones naturales. Zelman Waxman creía que este papel era mínimo, los antibióticos no se forman sino en culturas limpias en entornos ricos. Posteriormente, sin embargo, se descubrió que en muchos productos, la actividad de síntesis de antibióticos aumenta en presencia de otros tipos o productos específicos de su metabolismo.
Cir034 285.292
Clinical Practice Guidelines by the InfectiousDiseases Society of America for the Treatment ofMethicillin-Resistant Staphylococcus aureusInfections in Adults and Children: ExecutiveSummary
Catherine Liu,1 Arnold Bayer,3,5 Sara E. Cosgrove,6 Robert S. Daum,7 Scott K. Fridkin,8 Rachel J. Gorwitz,9Sheldon L. Kaplan,10 Adolf W. Karchmer,11 Donald P. Levine,12 Barbara E. Murray,14 Michael J. Rybak,12,13 DavidA. Talan,4,5 and Henry F. Chambers1,2
1Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California; 2Division of Infectious Diseases,
San Francisco General Hospital, San Francisco, CA, 3Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, 4Divisions of EmergencyMedicine and Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA; 5Department of Medicine, David Geffen School of Medicine at Universityof California Los Angeles; 6Division of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland; 7Department of Pediatrics, Sectionof Infectious Diseases, University of Chicago, Chicago, Illinois; 8,9Division of Healthcare Quality Promotion, Center for Emerging and Zoonotic Infectious
Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; 10Department of Pediatrics, Section of Infectious Diseases, Baylor College ofMedicine, Houston, Texas; 11Division of Infectious Diseases, Beth Israel Deaconess Medicine Center, Harvard Medical School, Boston, Massachusetts;12 Department of Medicine, Division of Infectious Diseases, Wayne State University, Detroit Receiving Hospital and University Health Center, Detroit,Michigan; 13Deparment of Pharmacy Practice, Wayne State University, Detroit Michigan; and 14Division of Infectious Diseases and Center for the Study of
Emerging and Re-emerging Pathogens, University of Texas Medical School, Houston, Texas
Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus(MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). Theguidelines are intended for use by health care providers who care for adult and pediatric patients with MRSAinfections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSAdisease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone andjoint infections, and central nervous system (CNS) infections. Recommendations are provided regardingvancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibilityto vancomycin, and vancomycin treatment failures.
treatment of MRSA infections. The primary objective ofthese guidelines is to provide recommendations on the
MRSA is a significant cause of both health care–associated
management of some of the most common clinical syn-
and community-associated infections. This document
dromes encountered by adult and pediatric clinicians who
constitutes the first guidelines of the IDSA on the
care for patients with MRSA infections. The guidelinesaddress issues related to the use of vancomycin therapy inthe treatment of MRSA infections, including dosing and
Received 28 October 2010; accepted 17 November 2010.
monitoring, current limitations of susceptibility testing,
Correspondence: Catherine Liu, MD, Dept of Medicine, Div of Infectious
Diseases, University of California–San Francisco, San Francisco, California, 94102
and the use of alternate therapies for those patients with
vancomycin treatment failure and infection due to strains
with reduced susceptibility to vancomycin. The guidelines
Ó The Author 2011. Published by Oxford University Press on behalf of theInfectious Diseases Society of America. All rights reserved. For Permissions,
do not discuss active surveillance testing or other
please e-mail:journals.permissions@oup.com.
MRSA infection–prevention strategies in health care set-
1058-4838/2011/523-0001$37.00DOI: 10.1093/cid/cir034
tings, which are addressed in previously published
MRSA Treatment Guidelines d CID 2011:52 (1 February) d 285
guidelines [1, 2]. Each section of the guidelines begins with
a tetracycline (doxycycline or minocycline) (A-II), and linezolid
a specific clinical question and is followed by numbered
(A-II). If coverage for both b-hemolytic streptococci and
recommendations and a summary of the most-relevant evidence
in support of the recommendations. Areas of controversy in
clindamycin alone (A-II) or TMP-SMX or a tetracycline in
which data are limited or conflicting and where additional re-
combination with a b-lactam (eg, amoxicillin) (A-II) or linezolid
search is needed are indicated throughout the document and are
highlighted in the Research Gaps section. The key recom-
The use of rifampin as a single agent or as adjunctive
mendations are summarized below in the Executive Summary;
therapy for the treatment of SSTI is not recommended (A-III).
each topic is discussed in greater detail within the main body of
For hospitalized patients with complicated SSTI (cSSTI;
defined as patients with deeper soft-tissue infections, surgical/
Please note that specific recommendations on vancomycin
traumatic wound infection, major abscesses, cellulitis, and
dosing and monitoring are not discussed in the sections for each
infected ulcers and burns), in addition to surgical debridement
clinical syndrome but are collectively addressed in detail in
MRSA should be considered pending culture data. Optionsinclude the following: intravenous (IV) vancomycin (A-I),
I. What is the management of skin and soft-tissue infections
oral (PO) or IV linezolid 600 mg twice daily (A-I),
(SSTIs) in the era of community-associated MRSA (CA-MRSA)?
daptomycin 4 mg/kg/dose IV once daily (A-I), telavancin
10 mg/kg/dose IV once daily (A-I), and clindamycin 600 mgIV or PO 3 times a day (A-III). A b-lactam antibiotic (eg,
For a cutaneous abscess, incision and drainage is the
cefazolin) may be considered in hospitalized patients with
primary treatment (A-II). For simple abscesses or boils,
nonpurulent cellulitis with modification to MRSA-active
incision and drainage alone is likely to be adequate, but
therapy if there is no clinical response (A-II). Seven to 14
additional data are needed to further define the role of
days of therapy is recommended but should be individualized
antibiotics, if any, in this setting.
on the basis of the patient’s clinical response.
Antibiotic therapy is recommended for abscesses associated
Cultures from abscesses and other purulent SSTIs are
with the following conditions: severe or extensive disease (eg,
recommended in patients treated with antibiotic therapy,
involving multiple sites of infection) or rapid progression in
patients with severe local infection or signs of systemic illness,
presence of associated cellulitis, signs and symptoms of systemic
patients who have not responded adequately to initial treatment,
and if there is concern for a cluster or outbreak (A-III).
extremes of age, abscess in an area difficult to drain (eg, face,hand, and genitalia), associated septic phlebitis, and lack of
response to incision and drainage alone (A-III).
For children with minor skin infections (such as impetigo)
For outpatients with purulent cellulitis (eg, cellulitis
and secondarily infected skin lesions (such as eczema, ulcers, or
associated with purulent drainage or exudate in the absence of
lacerations), mupirocin 2% topical ointment can be used (A-III).
a drainable abscess), empirical therapy for CA-MRSA is
Tetracyclines should not be used in children ,8 years of
recommended pending culture results. Empirical therapy for
infection due to b-hemolytic streptococci is likely to be
In hospitalized children with cSSTI, vancomycin is
unnecessary (A-II). Five to 10 days of therapy is recom-
recommended (A-II). If the patient is stable without ongoing
mended but should be individualized on the basis of the
bacteremia or intravascular infection, empirical therapy with
clindamycin 10–13 mg/kg/dose IV every 6–8 h (to administer
For outpatients with nonpurulent cellulitis (eg, cellulitis
40 mg/kg/day) is an option if the clindamycin resistance rate is
with no purulent drainage or exudate and no associated
low (eg, ,10%) with transition to oral therapy if the strain is
abscess), empirical therapy for infection due to b-hemolytic
susceptible (A-II). Linezolid 600 mg PO/IV twice daily for
streptococci is recommended (A-II). The role of CA-MRSA is
children >12 years of age and 10 mg/kg/dose PO/IV every 8 h
unknown. Empirical coverage for CA-MRSA is recommended
for children ,12 years of age is an alternative (A-II).
in patients who do not respond to b-lactam therapy and may beconsidered in those with systemic toxicity. Five to 10 days of
II. What is the management of recurrent MRSA SSTIs?
therapy is recommended but should be individualized on the
basis of the patient’s clinical response.
For empirical coverage of CA-MRSA in outpatients with
Preventive educational messages on personal hygiene
SSTI, oral antibiotic options include the following: clindamycin
and appropriate wound care are recommended for all patients
(A-II), trimethoprim-sulfamethoxazole (TMP-SMX) (A-II),
with SSTI. Instructions should be provided to:
286 d CID 2011:52 (1 February) d Liu et al
i. Keep draining wounds covered with clean, dry bandages
ii. Contacts should be evaluated for evidence of S. aureus
ii. Maintain good personal hygiene with regular bathing and
a. Symptomatic contacts should be evaluated and treated (A-
cleaning of hands with soap and water or an alcohol-based
III); nasal and topical body decolonization strategies may be
hand gel, particularly after touching infected skin or an item
considered following treatment of active infection (C-III).
that has directly contacted a draining wound (A-III).
b. Nasal and topical body decolonization of asymptomatic
iii. Avoid reusing or sharing personal items (eg, disposable
household contacts may be considered (C-III).
razors, linens, and towels) that have contacted infected skin
The role of cultures in the management of patients with
Environmental hygiene measures should be considered
i. Screening cultures prior to decolonization are not
in patients with recurrent SSTI in the household or community
routinely recommended if at least 1 of the prior infections
was documented as due to MRSA (B-III).
i. Focus cleaning efforts on high-touch surfaces (ie, surfaces
ii. Surveillance cultures following a decolonization regimen
that come into frequent contact with people’s bare skin each
are not routinely recommended in the absence of an active
day, such as counters, door knobs, bath tubs, and toilet seats)
that may contact bare skin or uncovered infections (C-III).
ii. Commercially available cleaners or detergents appropriate
III. What is the management of MRSA bacteremia and infective
for the surface being cleaned should be used according to label
instructions for routine cleaning of surfaces (C-III).
Bacteremia and Infective Endocarditis, Native Valve
Decolonization may be considered in selected cases if:
For adults with uncomplicated bacteremia (defined as
patients with positive blood culture results and the following:
i. A patient develops a recurrent SSTI despite optimizing
exclusion of endocarditis; no implanted prostheses; follow-up
wound care and hygiene measures (C-III).
blood cultures performed on specimens obtained 2–4 days
ii. Ongoing transmission is occurring among household
after the initial set that do not grow MRSA; defervescence
members or other close contacts despite optimizing wound
within 72 h of initiating effective therapy; and no evidence of
metastatic sites of infection), vancomycin (A-II) or daptomycin
Decolonization strategies should be offered in conjunction
6 mg/kg/dose IV once daily (AI) for at least 2 weeks. For
with ongoing reinforcement of hygiene measures and may
complicated bacteremia (defined as patients with positive blood
culture results who do not meet criteria for uncomplicatedbacteremia), 4–6 weeks of therapy is recommended, depending
i. Nasal decolonization with mupirocin twice daily for 5–10
on the extent of infection. Some experts recommend higher
dosages of daptomycin at 8–10 mg/kg/dose IV once daily (B-III).
ii. Nasal decolonization with mupirocin twice daily for 5–10
For adults with infective endocarditis, IV vancomycin
days and topical body decolonization regimens with a skin
(A-II) or daptomycin 6 mg/kg/dose IV once daily (A-I) for 6
antiseptic solution (eg, chlorhexidine) for 5–14 days or dilute
weeks is recommended. Some experts recommend higher
bleach baths. (For dilute bleach baths, 1 teaspoon per gallon
dosages of daptomycin at 8–10 mg/kg/dose IV once daily
of water [or ¼ cup per ¼ tub or 13 gallons of water] given
for 15 min twice weekly for 3 months can be considered.)
Addition of gentamicin to vancomycin is not recom-
mended for bacteremia or native valve infective endocarditis(A-II).
Oral antimicrobial therapy is recommended for the
Addition of rifampin to vancomycin is not recommen-
treatment of active infection only and is not routinely re-
ded for bacteremia or native valve infective endocarditis (A-I).
commended for decolonization (A-III). An oral agent in
A clinical assessment to identify the source and extent of
combination with rifampin, if the strain is susceptible, may be
the infection with elimination and/or debridement of other
considered for decolonization if infections recur despite above
sites of infection should be conducted (A-II).
Additional blood cultures 2–4 days after initial positive
In cases where household or interpersonal transmission
cultures and as needed thereafter are recommended to
document clearance of bacteremia (A-II).
i. Personal and environmental hygiene measures in the
Echocardiography is recommended for all adult
patient and contacts are recommended (A-III).
patients with bacteremia. Transesophageal echocardiography
MRSA Treatment Guidelines d CID 2011:52 (1 February) d 287
(TEE) is preferred over transthoracic echocardiography (TTE)
In patients with MRSA pneumonia complicated by
empyema, antimicrobial therapy against MRSA should be used
Evaluation for valve replacement surgery is recommen-
in conjunction with drainage procedures (A-III).
ded if large vegetation (.10 mm in diameter), occurrence of
>1 embolic event during the first 2 weeks of therapy, severevalvular insufficiency, valvular perforation or dehiscence,
In children, IV vancomycin is recommended (A-II). If
decompensated heart failure, perivalvular or myocardial
the patient is stable without ongoing bacteremia or intravas-
abscess, new heart block, or persistent fevers or bacteremia
cular infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h
(to administer 40 mg/kg/day) can be used as empirical therapyif the clindamycin resistance rate is low (eg, ,10%) with
transition to oral therapy if the strain is susceptible (A-II).
IV vancomycin plus rifampin 300 mg PO/IV every 8 h
Linezolid 600 mg PO/IV twice daily for children >12 years of
for at least 6 weeks plus gentamicin 1 mg/kg/dose IV every 8 h
age and 10 mg/kg/dose every 8 h for children ,12 years of age is
Early evaluation for valve replacement surgery is
V. What is the management of MRSA bone and joint infections?
Surgical debridement and drainage of associated soft-
tissue abscesses is the mainstay of therapy and should be
In children, vancomycin 15 mg/kg/dose IV every 6 h is
recommended for the treatment of bacteremia and infective
The optimal route of administration of antibiotic
endocarditis (A-II). Duration of therapy may range from 2 to
therapy has not been established. Parenteral, oral, or initial
6 weeks depending on source, presence of endovascular
parenteral therapy followed by oral therapy may be used
infection, and metastatic foci of infection. Data regarding the
depending on individual patient circumstances (A-III).
safety and efficacy of alternative agents in children are limited,
Antibiotics available for parenteral administration in-
although daptomycin 6–10 mg/kg/dose IV once daily may be
clude IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV
an option (C-III). Clindamycin or linezolid should not be
once daily (B-II). Some antibiotic options with parenteral and
used if there is concern for infective endocarditis or
oral routes of administration include the following: TMP-SMX
endovascular source of infection but may be considered in
4 mg/kg/dose (TMP component) twice daily in combination
children whose bacteremia rapidly clears and is not related to
with rifampin 600 mg once daily (B-II), linezolid 600 mg twice
daily (B-II), and clindamycin 600 mg every 8 h (B-III).
Data are insufficient to support the routine use of
Some experts recommend the addition of rifampin
combination therapy with rifampin or gentamicin in children
600 mg daily or 300–450 mg PO twice daily to the antibiotic
with bacteremia or infective endocarditis (C-III); the decision
chosen above (B-III). For patients with concurrent bacter-
to use combination therapy should be individualized.
emia, rifampin should be added after clearance of bacteremia.
Echocardiogram is recommended in children with con-
The optimal duration of therapy for MRSA osteomye-
genital heart disease, bacteremia more than 2–3 days in duration,
litis is unknown. A minimum 8-week course is recommended
or other clinical findings suggestive of endocarditis (A-III).
(A-II). Some experts suggest an additional 1–3 months (andpossibly longer for chronic infection or if debridement is not
IV. What is the management of MRSA pneumonia?
performed) of oral rifampin-based combination therapy with
TMP-SMX, doxycycline-minocycline, clindamycin, or a fluo-
For hospitalized patients with severe community-
roquinolone, chosen on the basis of susceptibilities (C-III).
acquired pneumonia defined by any one of the following: (1)
Magnetic resonance imaging (MRI) with gadolinium is
a requirement for intensive care unit (ICU) admission, (2)
the imaging modality of choice, particularly for detection of
necrotizing or cavitary infiltrates, or (3) empyema, empirical
early osteomyelitis and associated soft-tissue disease (A-II).
therapy for MRSA is recommended pending sputum and/or
Erythrocyte sedimentation rate (ESR) and/or C-reactive pro-
tein (CRP) level may be helpful to guide response to therapy
For health care–associated MRSA (HA-MRSA) or CA-
MRSA pneumonia, IV vancomycin (A-II) or linezolid 600 mg
PO/IV twice daily (A-II) or clindamycin 600 mg PO/IV 3 timesdaily (B-III), if the strain is susceptible, is recommended for 7–
Drainage or debridement of the joint space should
21 days, depending on the extent of infection.
288 d CID 2011:52 (1 February) d Liu et al
For septic arthritis, refer to antibiotic choices for
VI. What is the management of MRSA infections of the CNS?
osteomyelitis (recommendation 37 above). A 3–4-week course
IV vancomycin for 2 weeks is recommended (B-II).
Some experts recommend the addition of rifampin 600 mg
daily or 300–450 mg twice daily (B-III).
For early-onset (,2 months after surgery) or acute
Alternatives include the following: linezolid 600 mg PO/IV
hematogenous prosthetic joint infections involving a stable
twice daily (B-II) or TMP-SMX 5 mg/kg/dose IV every 8–12 h
implant with short duration (<3 weeks) of symptoms and
debridement (but device retention), initiate parenteral therapy
For CNS shunt infection, shunt removal is recommen-
(refer to antibiotic recommendations for osteomyelitis) plus
ded, and it should not be replaced until cerebrospinal fluid
rifampin 600 mg daily or 300–450 mg PO twice daily for 2
(CSF) cultures are repeatedly negative (A-II).
weeks followed by rifampin plus a fluoroquinolone, TMP-SMX, a tetracycline or clindamycin for 3 or 6 months for hips
Brain abscess, subdural empyema, spinal epidural abscess
and knees, respectively (A-II). Prompt debridement with device
Neurosurgical evaluation for incision and drainage is
removal whenever feasible is recommended for unstable
implants, late-onset infections, or in those with long duration
IV vancomycin for 4–6 weeks is recommended (B-II).
Some experts recommend the addition of rifampin 600 mg
For early-onset spinal implant infections (<30 days after
daily or 300–450 mg twice daily (B-III).
surgery) or implants in an actively infected site, initial
Alternatives include the following: linezolid 600 mg PO/IV
parenteral therapy plus rifampin followed by prolonged oral
twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h
therapy is recommended (B-II). The optimal duration of
parenteral and oral therapy is unclear; the latter should be
continued until spine fusion has occurred (B-II). For late-onset
Septic Thrombosis of Cavernous or Dural Venous Sinus
infections (.30 days after implant placement), device removal
Surgical evaluation for incision and drainage of contig-
whenever feasible is recommended (B-II).
uous sites of infection or abscess is recommended whenever
Long-term oral suppressive antibiotics (eg, TMP-SMX,
possible (A-II). The role of anticoagulation is controversial.
a tetracycline, a fluoroquinolone [which should be given in
IV vancomycin for 4–6 weeks is recommended (B-II).
conjunction with rifampin due to the potential emergence of
Some experts recommend the addition of rifampin 600 mg
fluoroquinolone resistance, particularly if adequate surgical
daily or 300–450 mg twice daily (B-III).
debridement is not possible should be given in conjunction
Alternatives include the following: linezolid 600 mg PO/IV
with rifampin], or clindamycin) with or without rifampin may
twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 h
be considered in selected cases, particularly if device removal
IV vancomycin is recommended (A-II).
osteomyelitis and septic arthritis, IV vancomycin is recom-
VII. What is the role of adjunctive therapies for the treatment ofMRSA infections?
mended (A-II). If the patient is stable without ongoingbacteremia or intravascular infection, clindamycin 10–13 mg/
Protein synthesis inhibitors (eg, clindamycin and line-
kg/dose IV every 6–8 h (to administer 40 mg/kg/day) can be
zolid) and intravenous immunoglobulin (IVIG) are not
used as empirical therapy if the clindamycin resistance rate is
routinely recommended as adjunctive therapy for the manage-
low (eg, ,10%) with transition to oral therapy if the strain is
ment of invasive MRSA disease (A-III). Some experts may
susceptible (A-II). The exact duration of therapy should be
consider these agents in selected scenarios (eg, necrotizing
individualized, but typically a minimum 3–4-week course is
pneumonia or severe sepsis) (C-III).
recommended for septic arthritis and a 4–6-week course isrecommended for osteomyelitis.
VIII. What are the recommendations for vancomycin dosing and
Alternatives to vancomycin and clindamycin include the
following: daptomycin 6 mg/kg/day IV once daily (C-III) or
These recommendations are based on a consensus statement of
linezolid 600 mg PO/IV twice daily for children >12 years of
the American Society of Health-System Pharmacists, the IDSA,
age and 10 mg/kg/dose every 8 h for children ,12 years of age
and The Society of Infectious Diseases Pharmacists on guidelines
MRSA Treatment Guidelines d CID 2011:52 (1 February) d 289
i. If the patient has had a clinical and microbiologic response
IV vancomycin 15–20 mg/kg/dose (actual body weight)
to vancomycin, then it may be continued with close follow-up
every 8–12 h, not to exceed 2 g per dose, is recommended in
ii. If the patient has not had a clinical or microbiologic
patients with normal renal function (B-III).
response to vancomycin despite adequate debridement and
In seriously ill patients (eg, those with sepsis, meningitis,
removal of other foci of infection, an alternative to vancomycin
pneumonia, or infective endocarditis) with suspected MRSA
infection, a loading dose of 25–30 mg/kg (actual body weight)
For isolates with a vancomycin MIC .2 lg/mL (eg,
may be considered. (Given the risk of red man syndrome and
vancomycin-intermediate S. aureus [VISA] or vancomycin-
possible anaphylaxis associated with large doses of vancomycin,
resistant S. aureus [VRSA]), an alternative to vancomycin
one should consider prolonging the infusion time to 2 h and
use of an antihistamine prior to administration of the loading
X. What is the management of persistent MRSA bacteremia and
vancomycin treatment failures in adult patients?
Trough vancomycin concentrations are the most
accurate and practical method to guide vancomycin dosing
A search for and removal of other foci of infection,
(B-II). Serum trough concentrations should be obtained at
drainage or surgical debridement is recommended (A-III).
steady state conditions, prior to the fourth or fifth dose.
High-dose daptomycin (10 mg/kg/day), if the isolate is
Monitoring of peak vancomycin concentrations is not
susceptible, in combination with another agent (e.g. gentamicin
1 mg/kg IV every 8 h, rifampin 600 mg PO/IV daily or
For serious infections, such as bacteremia, infective
300-450 mg PO/IV twice daily, linezolid 600 mg PO/IV BID,
endocarditis, osteomyelitis, meningitis, pneumonia, and severe
TMP-SMX 5 mg/kg IV twice daily, or a beta-lactam antibiotic)
SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin
trough concentrations of 15–20 lg/mL are recommended
If reduced susceptibility to vancomycin and daptomycin
are present, options may include the following: quinupristin-
For most patients with SSTI who have normal renal
dalfopristin 7.5 mg/kg/dose IV every 8 h, TMP-SMX 5 mg/kg/
function and are not obese, traditional doses of 1 g every 12 h
dose IV twice daily, linezolid 600 mg PO/IV twice daily, or
are adequate, and trough monitoring is not required (B-II).
telavancin 10 mg/kg/dose IV once daily (C-III). These options
Trough vancomycin monitoring is recommended for
may be given as a single agent or in combination with other
serious infections and patients who are morbidly obese, have
renal dysfunction (including those receiving dialysis), or havefluctuating volumes of distribution (A-II).
XI. What is the management of MRSA infections in neonates?
Continuous infusion vancomycin regimens are not
For mild cases with localized disease, topical treatment
with mupirocin may be adequate in full-term neonates andyoung infants (A-III).
Data are limited to guide vancomycin dosing in
For localized disease in a premature or very low-
children. IV vancomycin 15 mg/kg/dose every 6 h is
birthweight infant or more-extensive disease involving multiple
recommended in children with serious or invasive disease
sites in full-term infants, IV vancomycin or clindamycin is
recommended, at least initially, until bacteremia is excluded
The efficacy and safety of targeting trough concentrations
of 15–20 lg/mL in children requires additional study but shouldbe considered in those with serious infections, such as
bacteremia, infective endocarditis, osteomyelitis, meningitis,
IV vancomycin is recommended, dosing as outlined in
pneumonia, and severe SSTI (ie, necrotizing fasciitis) (B-III).
Clindamycin and linezolid are alternatives for non-
IX. How should results of vancomycin susceptibility testing be
The prevalence of MRSA has steadily increased since the first
For isolates with a vancomycin minimum inhibitory
clinical isolate was described in 1961, with an estimated 94,360
concentration (MIC) <2 lg/mL (eg, susceptible according to
cases of invasive MRSA disease in the United States in 2005 [5].
Clinical and Laboratory Standards Institute [CLSI] breakpoints),
Initially almost exclusively health care–associated, by the mid-
the patient’s clinical response should determine the continued
1990s, MRSA strains were reported as causing infections among
use of vancomycin, independent of the MIC (A-III).
previously healthy individuals in the community who lacked
290 d CID 2011:52 (1 February) d Liu et al
health care–associated risk factors [6]. Unlike HA-MRSA, these
so-called CA-MRSA isolates are susceptible to many non–ß-
The Expert Panel wishes to express its gratitude to Drs. Gordon Archer,
lactam antibiotics. Furthermore, they are genetically distinct
Frank Lowy, and Brad Spellberg for their thoughtful reviews of earlier drafts
from HA-MRSA isolates and contain a novel cassette element,
of the guideline. The Expert Panel also recognizes the following for theirimportant contributions in identifying critical gaps where funding of re-
SCCmec IV and exotoxin, Panton-Valentine leukocidin (PVL).
search is needed to advance clinical treatment and care: William Burman,
The epidemiology of MRSA has become increasingly complex as
David M. Margolis, and Louis B. Rice (IDSA Research Committee), Stanley
CA-MRSA and HA-MRSA strains have co-mingled both in the
C. Deresinski (IDSA SPGC), and Padma Natarajan (IDSA staff). Thefindings and conclusions of this report are those of the authors and do not
community and in health care facilities [7, 8]. Not unexpectedly,
necessarily represent the official position of the Centers for Disease Control
MRSA disease has had an enormous clinical and economic
It is important to realize that guidelines cannot always account for individual
variation among patients. They are not intended to supplant physician judgment
The wide spectrum of illness caused by MRSA includes SSTIs,
with respect to particular patients or special clinical situations. The IDSA con-
bacteremia and endocarditis, pneumonia, bone and joint in-
siders adherence to these guidelines to be voluntary, with the ultimate de-
fections, CNS disease, and toxic shock and sepsis syndromes.
termination regarding their application to be made by the physician in the light ofeach patient’s individual circumstances.
CA-MRSA was the most common cause of SSTI in a geo-
graphically diverse network of emergency departments in the
United States [11]; however, there may be differences in local
search grants and has served as a consultant to Cubist, Ortho-McNeil,Pfizer, Theravance, and Targanta. S. E. C. has received honoraria from
epidemiology to consider when implementing these guidelines.
Forest and RibX, has served as a consultant for Merck and has received
SSTIs may range in clinical presentation from a simple abscess
research support from Astellas, Cubist and AdvanDx. R.D. has received
or cellulitis to deeper soft-tissue infections, such as pyomyositis,
research funding from Pfizer, Clorox, Sanofi Pasteur, Sage, and GeneOhm. S.L.K. has received grant funding from Pfizer, has served as MRSA Lead-
necrotizing fasciitis, and mediastinitis as a complication of ret-
ership Advisor to Pfizer, and is participating in a pediatric daptomycin
ropharyngeal abscess [12–15]. Bacteremia accompanies the
study. A.W.K. has received honoraria and grants from Cubist Pharma-
majority (75%) of cases of invasive MRSA disease [5]. A mul-
ceuticals, Merck, Wyeth, and Pfizer and has served as a consultant forCubist Pharmaceuticals, Theravance, Astellas, Pfizer, Merck, and Ortho-
titude of disease manifestations have been described, including,
McNeil and has owned stock from Cubist Pharmaceutical, Pfizer, and
but not limited to, infective endocarditis; myocardial, peri-
Johnson and Johnson. D.P.L. has received research support from Cubist,Johnson & Johnson, and Theravance and has served as a speaker for Cubist.
nephric, hepatic, and splenic abscesses; septic thrombophlebitis
B.E.M. has served as a consultant and received research support from
with and without pulmonary emboli [16]; necrotizing pneu-
Johnson & Johnson, Astellas, Pfizer, Cubist, Theravance, Targanta, Sanofi-
monia [17–21]; osteomyelitis complicated by subperiosteal ab-
Aventis, Vicuron Pharmaceuticals, and Wyeth-Ayerst. M.R. has receivedgrants and or has served as a consultant speaker for the Pfizer, Cubist,
scesses; venous thrombosis and sustained bacteremia [16, 22,
Theravance/Astellas, Targanta, and Johnson & Johnson. D.A.T. has served
23]; severe ocular infections, including endophthalmitis [24];
on the advisory board to Pfizer, Ortho-McNeil, Astellas, Schering-Plough,
sepsis with purpura fulminans [25]; and Waterhouse-Frider-
and Replidyne. All other authors: no conflicts.
The Expert Panel addressed the following clinical questions in
1. Calfee DP, Salgado CD, Classen D, et al. Strategies to prevent trans-
mission of methicillin-resistant Staphylococcus aureus in acute care
I. What is the management of SSTIs in the CA-MRSA era?
hospitals. Infect Control Hosp Epidemiol 2008; 29(Suppl 1):S62–S80.
2. Anderson DJ, Kaye KS, Classen D, et al. Strategies to prevent surgical
II. What is the management of recurrent MRSA SSTIs?
site infections in acute care hospitals. Infect Control Hosp Epidemiol
III. What is the management of MRSA bacteremia and
3. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of
IV. What is the management of MRSA pneumonia?
vancomycin in adult patients: a consensus review of the AmericanSociety of Health-System Pharmacists, the Infectious Diseases Society
V. What is the management of MRSA bone and joint
of America, and the Society of Infectious Diseases Pharmacists. Am J
VI. What is the management of MRSA infections of the CNS?
4. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin thera-
peutic guidelines: a summary of consensus recommendations from the
VII. What is the role of adjunctive therapies for the treatment
Infectious Diseases Society of America, the American Society of
Health-System Pharmacists, and the Society of Infectious Diseases
VIII. What are the recommendations for vancomycin dosing
Pharmacists. Clin Infect Dis 2009; 49:325–7.
5. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant
Staphylococcus aureus infections in the United States. JAMA 2007;
IX. How should results of vancomycin susceptibility testing be
6. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired
X. What is the management of persistent MRSA bacteremia
methicillin-resistant Staphylococcus aureus in children with no identi-fied predisposing risk. JAMA 1998; 279:593–8.
7. Liu C, Graber CJ, Karr M, et al. A population-based study of
XI. What is the management of MRSA in neonates?
the incidence and molecular epidemiology of methicillin-resistant
MRSA Treatment Guidelines d CID 2011:52 (1 February) d 291
Staphylococcus aureus disease in San Francisco, 2004–2005. Clin Infect
17. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset
pneumonia in healthy adults caused by methicillin-resistant Staphylo-
8. D’Agata EM, Webb GF, Horn MA, et al. Modeling the invasion of
coccus aureus carrying the Panton-Valentine leukocidin genes. Clin
community-acquired methicillin-resistant Staphylococcus aureus into
hospitals. Clin Infect Dis 2009; 48:274–84.
18. Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired
9. Purcell K, Fergie J, Peterson MD. Economic impact of the community-
pneumonia due to Staphylococcus aureus, 2003-04 influenza season.
acquired methicillin-resistant Staphylococcus aureus epidemic on
the Driscoll Children’s Health Plan. Pediatr Infect Dis J 2006; 25:
19. Centers for Disease Control and Prevention. Severe methicillin-re-
sistant Staphylococcus aureus community-acquired pneumonia associ-
10. Noskin GA, Rubin RJ, Schentag JJ, et al. The burden of Staphylococcus
ated with influenza–Louisiana Georgia, December 2006-January 2007.
aureus infections on hospitals in the United States: an analysis of the
MMWR Morb Mortal Wkly Rep 2007; 56:325–9.
2000 and 2001 Nationwide Inpatient Sample Database. Arch Intern
20. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonary manifestations
in children with invasive community-acquired Staphylococcus aureus
11. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S.
infection. Clin Infect Dis 2005; 41:583–90.
aureus infections among patients in the emergency department. N Engl
21. Finelli L, Fiore A, Dhara R, et al. Influenza-associated pediatric mor-
tality in the United States: increase of Staphylococcus aureus co-
12. Lee TC, Carrick MM, Scott BG, et al. Incidence and clinical charac-
infection. Pediatrics 2008; 122:805–11.
teristics of methicillin-resistant Staphylococcus aureus necrotizing fas-
22. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute
ciitis in a large urban hospital. Am J Surg 2007; 194:809–12; discussion,
hematogenous osteomyelitis and septic arthritis: emergence of com-
munity-associated methicillin-resistant Staphylococcus aureus. J Pediatr
13. Pannaraj PS, Hulten KG, Gonzalez BE, et al. Infective pyomyositis and
myositis in children in the era of community-acquired, methicillin-
23. Crary SE, Buchanan GR, Drake CE, et al. Venous thrombosis and
resistant Staphylococcus aureus infection. Clin Infect Dis 2006; 43:953–60.
thromboembolism in children with osteomyelitis. J Pediatr 2006;
14. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis
caused by community-associated methicillin-resistant Staphylococcus
24. Rutar T, Chambers HF, Crawford JB, et al. Ophthalmic manifestations
aureus in Los Angeles. N Engl J Med 2005; 352:1445–53.
of infections caused by the USA300 clone of community-associated
15. Wright CT, Stocks RM, Armstrong DL, et al. Pediatric mediastinitis as
methicillin-resistant Staphylococcus aureus. Ophthalmology 2006;
a complication of methicillin-resistant Staphylococcus aureus retro-
pharyngeal abscess. Arch Otolaryngol Head Neck Surg 2008;
25. Kravitz GR, Dries DJ, Peterson ML, et al. Purpura fulminans due to
Staphylococcus aureus. Clin Infect Dis 2005; 40:941–7.
16. Gonzalez BE, Teruya J, Mahoney DH Jr., et al. Venous thrombosis
26. Adem PV, Montgomery CP, Husain AN, et al. Staphylococcus aureus
associated with staphylococcal osteomyelitis in children. Pediatrics
sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J
292 d CID 2011:52 (1 February) d Liu et al
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