Professional Documents
Culture Documents
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 careassociated 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 infectionprevention strategies in health care set-
Correspondence: Catherine Liu, MD, Dept of Medicine, Div of Infectious
Diseases, University of CaliforniaSan 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):e18e55 with a specific clinical question and is followed by
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
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
dividuals 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 [4245]. 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, 2931]. 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 [3234]. 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 difficileassociated disease may occur more frequently, activity against VISA and VRSA [5355]. 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
d
to exceed 600 mg/dose
e29
Table 3. (Continued)
e30 d
Manifestation Treatment Adult dose Pediatric dose Classa Comment
Provide coverage for both
B-hemolytic streptococci
and CA-MRSA
Complicated SSTI Vancomycin 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AI/AII
812 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
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 1013 mg/kg/dose PO/IV every AIII/AII Pregnancy category B
68 h, not to exceed
40 mg/kg/day
Bacteremia and infective
endocarditis
Bacteremia Vancomycin 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AII The addition of gentamicin (AII)
812 h or rifampin (AI) to vancomycin
is not routinely recommended.
Daptomycin 6 mg/kg/dose IV QD 610 mg/kg/dose IV QD AI/CIII For adult patients, some
experts recommend higher
dosages of 810 mg/kg/dose
IV QD (BIII). Pregnancy cate-
gory B.
Infective endocarditis, Same as for bacteremia
native valve
Infective endocarditis, Vancomycin and 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BIII
prosthetic valve gentamicin and rifampin 812 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 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h AII
812 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 1013 mg/kg/dose PO/IV every BIII/AII Pregnancy category B.
68 h, not to exceed 40 mg/kg/
day
Table 3. (Continued)
Manifestation Treatment Adult dose Pediatric dose Classa Comment
d
Clindamycin 600 mg PO/IV TID 1013 mg/kg/dose PO/IV every BIII/AII
68 h, not to exceed
40 mg/kg/day
TMP-SMX 3.54.0 mg/kg/dose PO/IV ND BIII/ND
every 812 h
Prosthetic joint, spinal Please see text
implant infections
Central nervous system
infections
Meningitis Vancomycin 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
812 h addition of rifampin 600 mg
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 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
empyema, spinal 812 h addition of rifampin 600 mg
epidural abscess QD or 300450 mg BID to
vancomycin for adult patients
(BIII). For children >12 years
of age, linezolid 600 mg BID.
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 ND CIII/ND
every 812 h
Septic thrombosis of Vancomycin 1520 mg/kg/dose IV every 15 mg/kg/dose IV every 6 h BII Some experts recommend the
cavernous or dural 812 h addition of rifampin 600 mg
venous sinus QD or 300450 mg BID to
vancomycin for adult patients
(BIII). For children >12 years
of age, linezolid 600 mg BID
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
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, 136138]. 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 510
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 514 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 cup per 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 714
considered for decolonization if infections recur despite above
days. Duration of therapy should be individualized on the basis
measures (CIII).
of the patients 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 peoples 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