Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin resistant staphylococcus aureus infections in adults and children
Clinical Infectious Diseases Advance Access published January 4, 2011 IDSA GUIDELINESClinical Practice Guidelines by the InfectiousDiseases Society of America for the Treatment ofMethicillin-Resistant Staphylococcus AureusInfections in Adults and ChildrenCatherine 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. Chambers1,21Department 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 Downloaded from cid.oxfordjournals.org by guest on February 6, 2011Medicine 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 InfectiousDiseases, 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 ofEmerging and Re-emerging Pathogens, University of Texas Medical School, Houston, TexasEvidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus(MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). Theguidelines are intended for use by health care providers who care for adult and pediatric patients with MRSAinfections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSAdisease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone andjoint infections, and central nervous system (CNS) infections. Recommendations are provided regardingvancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibilityto vancomycin, and vancomycin treatment failures.EXECUTIVE SUMMARY constitutes the ﬁrst guidelines of the IDSA on the treat- ment of MRSA infections. The primary objective of theseMRSA is a signiﬁcant cause of both health care–associated guidelines is to provide recommendations on the man-and community-associated infections. This document agement of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for Received 28 October 2010; accepted 17 November 2010. patients with MRSA infections. The guidelines address It is important to realize that guidelines cannot always account for individualvariation among patients. They are not intended to supplant physician judgment issues related to the use of vancomycin therapy in thewith respect to particular patients or special clinical situations. The IDSA considers treatment of MRSA infections, including dosing andadherence to these guidelines to be voluntary, with the ultimate determinationregarding their application to be made by the physician in the light of each monitoring, current limitations of susceptibility testing,patients individual circumstances. and the use of alternate therapies for those patients with Correspondence: Catherine Liu, MD, Dept of Medicine, Div of InfectiousDiseases, University of California–San Francisco, San Francisco, California, 94102 vancomycin treatment failure and infection due to strains(email@example.com). with reduced susceptibility to vancomycin. The guidelinesClinical Infectious Diseases 2011;1–38Ó The Author 2011. Published by Oxford University Press on behalf of the do not discuss active surveillance testing or otherInfectious Diseases Society of America. All rights reserved. For Permissions, MRSA infection–prevention strategies in health care set-please e-mail:firstname.lastname@example.org/2011/523-0001$37.00 tings, which are addressed in previously publishedDOI: 10.1093/cid/ciq146 guidelines [1, 2]. Each section of the guidelines begins Clinical Practice Guidelines d CID 2011:52 (1 February) d 1
with a speciﬁc clinical question and is followed by numbered a tetracycline (doxycycline or minocycline) (A-II), and linezolidrecommendations and a summary of the most-relevant evidence (A-II). If coverage for both b-hemolytic streptococci andin support of the recommendations. Areas of controversy in CA-MRSA is desired, options include the following:which data are limited or conﬂicting and where additional re- clindamycin alone (A-II) or TMP-SMX or a tetracycline insearch is needed are indicated throughout the document and are combination with a b-lactam (eg, amoxicillin) (A-II) or linezolidhighlighted in the Research Gaps section. The key recom- alone (A-II).mendations are summarized below in the Executive Summary; 6. The use of rifampin as a single agent or as adjunctiveeach topic is discussed in greater detail within the main body of therapy for the treatment of SSTI is not recommended (A-III).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, andclinical syndrome but are collectively addressed in detail in infected ulcers and burns), in addition to surgical debridementSection VIII. and broad-spectrum antibiotics, empirical therapy for MRSA should be considered pending culture data. OptionsI. 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), daptomycinSSTIs 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 Downloaded from cid.oxfordjournals.org by guest on February 6, 2011 a day (A-III). A b-lactam antibiotic (eg, cefazolin) may beprimary treatment (A-II). For simple abscesses or boils, considered in hospitalized patients with nonpurulent cellulitisincision and drainage alone is likely to be adequate, but with modiﬁcation to MRSA-active therapy if there is no clinicaladditional data are needed to further deﬁne the role of response (A-II). Seven to 14 days of therapy is recommendedantibiotics, 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 aredisease (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), associatedseptic phlebitis, and lack of response to incision and drainage Pediatric considerationsalone (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, orassociated 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 ofrecommended 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 isunnecessary (A-II). Five to 10 days of therapy is recom- recommended (A-II). If the patient is stable without ongoingmended but should be individualized on the basis of the bacteremia or intravascular infection, empirical therapy withpatient’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 iswith no purulent drainage or exudate and no associated low (eg, ,10%) with transition to oral therapy if the strain isabscess), empirical therapy for infection due to b-hemolytic susceptible (A-II). Linezolid 600 mg PO/IV twice daily forstreptococci is recommended (A-II). The role of CA-MRSA is children >12 years of age and 10 mg/kg/dose PO/IV every 8 hunknown. 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 Recurrent SSTIsbasis of the patient’s clinical response. 5. For empirical coverage of CA-MRSA in outpatients with 12. Preventive educational messages on personal hygieneSSTI, 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:2 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(A-III). infection: 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 behand 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 18. The role of cultures in the management of patients with(A-III). recurrent SSTI is limited: 13. Environmental hygiene measures should be considered i. Screening cultures prior to decolonization are notin patients with recurrent SSTI in the household or community routinely recommended if at least 1 of the prior infectionssetting: was documented as due to MRSA (B-III). i. Focus cleaning efforts on high-touch surfaces (ie, surfaces ii. Surveillance cultures following a decolonization regimenthat come into frequent contact with people’s bare skin each are not routinely recommended in the absence of an activeday, such as counters, door knobs, bath tubs, and toilet seats) infection (B-III).that may contact bare skin or uncovered infections (C-III). III. What is the management of MRSA bacteremia and infective ii. Commercially available cleaners or detergents appropriate endocarditis? Downloaded from cid.oxfordjournals.org by guest on February 6, 2011for the surface being cleaned should be used according to label Bacteremia and Infective Endocarditis, Native Valveinstructions for routine cleaning of surfaces (C-III). 19. For adults with uncomplicated bacteremia (deﬁned as 14. Decolonization may be considered in selected cases if: patients with positive blood culture results and the following: 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 dayswound care and hygiene measures (C-III). ii. Ongoing transmission is occurring among household after the initial set that do not grow MRSA; defervescencemembers or other close contacts despite optimizing wound within 72 h of initiating effective therapy; and no evidence ofcare and hygiene measures (C-III). metastatic sites of infection), vancomycin (A-II) or daptomycin 6 mg/kg/dose IV once daily (AI) for at least 2 weeks. For 15. Decolonization strategies should be offered in conjunction complicated bacteremia (deﬁned as patients with positive bloodwith ongoing reinforcement of hygiene measures and may culture results who do not meet criteria for uncomplicatedinclude the following: bacteremia), 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 higherdays (C-III). dosages of daptomycin at 8–10 mg/kg/dose IV once daily (B-III). ii. Nasal decolonization with mupirocin twice daily for 5–10 20. For adults with infective endocarditis, IV vancomycindays and topical body decolonization regimens with a skin (A-II) or daptomycin 6 mg/kg/dose IV once daily (A-I) for 6antiseptic solution (eg, chlorhexidine) for 5–14 days or dilute weeks is recommended. Some experts recommend higherbleach baths. (For dilute bleach baths, 1 teaspoon per gallon dosages of daptomycin at 8–10 mg/kg/dose IV once dailyof water [or ¼ cup per ¼ tub or 13 gallons of water] given (B-III).for 15 min twice weekly for $3 months can be considered.) 21. Addition of gentamicin to vancomycin is not recom-(C-III). mended for bacteremia or native valve infective endocarditis (A-II). 16. Oral antimicrobial therapy is recommended for the 22. 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 23. A clinical assessment to identify the source and extent ofcombination with rifampin, if the strain is susceptible, may be the infection with elimination and/or debridement of otherconsidered for decolonization if infections recur despite above sites of infection should be conducted (A-II).measures (CIII). 24. Additional blood cultures 2–4 days after initial positive 17. In cases where household or interpersonal transmission cultures and as needed thereafter are recommended tois suspected: document clearance of bacteremia (A-II). i. Personal and environmental hygiene measures in the 25. Echocardiography is recommended for all adultpatient and contacts are recommended (A-III). patients with bacteremia. Transesophageal echocardiography Clinical Practice Guidelines d CID 2011:52 (1 February) d 3
(TEE) is preferred over transthoracic echocardiography (TTE) 34. In patients with MRSA pneumonia complicated by(A-II). empyema, antimicrobial therapy against MRSA should be used 26. Evaluation for valve replacement surgery is recommen- in conjunction with drainage procedures (A-III).ded if large vegetation (.10 mm in diameter), occurrence of Pediatric considerations>1 embolic event during the ﬁrst 2 weeks of therapy, severevalvular insufﬁciency, valvular perforation or dehiscence, 35. In children, IV vancomycin is recommended (A-II). Ifdecompensated 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 hare present (A-II). (to administer 40 mg/kg/day) can be used as empirical therapy if the clindamycin resistance rate is low (eg, ,10%) withInfective Endocarditis, Prosthetic Valve transition to oral therapy if the strain is susceptible (A-II). 27. IV vancomycin plus rifampin 300 mg PO/IV every 8 h Linezolid 600 mg PO/IV twice daily for children >12 years offor 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 isfor 2 weeks (B-III). an alternative (A-II). 28. Early evaluation for valve replacement surgery is V. What is the management of MRSA bone and joint infections?recommended (A-II). OsteomyelitisPediatric considerations 36. Surgical debridement and drainage of associated soft- Downloaded from cid.oxfordjournals.org by guest on February 6, 2011 tissue abscesses is the mainstay of therapy and should be 29. In children, vancomycin 15 mg/kg/dose IV every 6 h is performed whenever feasible (A-II).recommended for the treatment of bacteremia and infective 37. The optimal route of administration of antibioticendocarditis (A-II). Duration of therapy may range from 2 to 6 therapy has not been established. Parenteral, oral, or initialweeks depending on source, presence of endovascular infection, parenteral therapy followed by oral therapy may be usedand metastatic foci of infection. Data regarding the safety and depending on individual patient circumstances (A-III).efﬁcacy of alternative agents in children are limited, although 38. Antibiotics available for parenteral administration in-daptomycin 6–10 mg/kg/dose IV once daily may be an option clude IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV(C-III). Clindamycin or linezolid should not be used if there is once daily (B-II). Some antibiotic options with parenteral andconcern for infective endocarditis or endovascular source of oral routes of administration include the following: TMP-SMXinfection but may be considered in children whose bacteremia 4 mg/kg/dose (TMP component) twice daily in combinationrapidly clears and is not related to an endovascular focus (B-III). with rifampin 600 mg once daily (B-II), linezolid 600 mg twice 30. Data are insufﬁcient to support the routine use of daily (B-II), and clindamycin 600 mg every 8 h (B-III).combination therapy with rifampin or gentamicin in children 39. Some experts recommend the addition of rifampinwith bacteremia or infective endocarditis (C-III); the decision 600 mg daily or 300–450 mg PO twice daily to the antibioticto use combination therapy should be individualized. chosen above (B-III). For patients with concurrent bacter- 31. Echocardiogram is recommended in children with con- emia, rifampin should be added after clearance of bacteremia.genital heart disease, bacteremia more than 2–3 days in duration, 40. The optimal duration of therapy for MRSA osteomye-or other clinical ﬁndings suggestive of endocarditis (A-III). litis is unknown. A minimum 8-week course is recommended (A-II). Some experts suggest an additional 1–3 months (andIV. What is the management of MRSA pneumonia? possibly longer for chronic infection or if debridement is notPneumonia performed) of oral rifampin-based combination therapy with 32. For hospitalized patients with severe community- TMP-SMX, doxycycline-minocycline, clindamycin, or a ﬂuo-acquired pneumonia deﬁned by any one of the following: (1) roquinolone, chosen on the basis of susceptibilities (C-III).a requirement for intensive care unit (ICU) admission, (2) 41. Magnetic resonance imaging (MRI) with gadolinium isnecrotizing or cavitary inﬁltrates, or (3) empyema, empirical the imaging modality of choice, particularly for detection of 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 mgPO/IV twice daily (A-II) or clindamycin 600 mg PO/IV 3 times Septic Arthritisdaily (B-III), if the strain is susceptible, is recommended for 7– 42. Drainage or debridement of the joint space should21 days, depending on the extent of infection. always be performed (A-II).4 d CID 2011:52 (1 February) d Liu et al.
43. 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 Meningitisof therapy is suggested (A-III). 49. IV vancomycin for 2 weeks is recommended (B-II).Device-related osteoarticular infections Some experts recommend the addition of rifampin 600 mg daily or 300–450 mg twice daily (B-III). 44. For early-onset (,2 months after surgery) or acute 50. Alternatives include the following: linezolid 600 mg PO/IVhematogenous prosthetic joint infections involving a stable twice daily (B-II) or TMP-SMX 5 mg/kg/dose IV every 8–12 himplant with short duration (<3 weeks) of symptoms and (C-III).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 ﬂuidrifampin 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 abscessand knees, respectively (A-II). Prompt debridement with device 52. Neurosurgical evaluation for incision and drainage isremoval 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). Downloaded from cid.oxfordjournals.org by guest on February 6, 2011surgery) or implants in an actively infected site, initial 54. Alternatives include the following: linezolid 600 mg PO/IVparenteral therapy plus rifampin followed by prolonged oral twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 htherapy 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 Sinuscontinued until spine fusion has occurred (B-II). For late-onsetinfections (.30 days after implant placement), device removal 55. Surgical evaluation for incision and drainage of contig- uous sites of infection or abscess is recommended wheneverwhenever feasible is recommended (B-II). 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). Some experts recommend the addition of rifampin 600 mgconjunction with rifampin due to the potential emergence of daily or 300–450 mg twice daily (B-III).ﬂuoroquinolone resistance, particularly if adequate surgical 57. Alternatives include the following: linezolid 600 mg PO/IVdebridement is not possible should be given in conjunction twice daily (B-II) and TMP-SMX 5 mg/kg/dose IV every 8–12 hwith rifampin], or clindamycin) with or without rifampin may (C-III).be considered in selected cases, particularly if device removalnot possible (B-III). Pediatric considerationsPediatric considerations 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 oflitis and septic arthritis, IV vancomycin is recommended (A-II). If MRSA infections?the patient is stable without ongoing bacteremia or intravascular 59. Protein synthesis inhibitors (eg, clindamycin and line-infection, clindamycin 10–13 mg/kg/dose IV every 6–8 h (to zolid) and intravenous immunoglobulin (IVIG) are notadminister 40 mg/kg/day) can be used as empirical therapy if the routinely recommended as adjunctive therapy for the manage-clindamycin resistance rate is low (eg, ,10%) with transition to ment of invasive MRSA disease (A-III). Some experts mayoral therapy if the strain is susceptible (A-II). The exact consider these agents in selected scenarios (eg, necrotizingduration of therapy should be individualized, but typically pneumonia or severe sepsis) (C-III).a minimum 3–4-week course is recommended for septic arthritisand 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 oflinezolid 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]. Clinical Practice Guidelines d CID 2011:52 (1 February) d 5
Adults i. If the patient has had a clinical and microbiologic response 60. IV vancomycin 15–20 mg/kg/dose (actual body weight) to vancomycin, then it may be continued with close follow-upevery 8–12 h, not to exceed 2 g per dose, is recommended in ii. If the patient has not had a clinical or microbiologicpatients with normal renal function (B-III). response to vancomycin despite adequate debridement and 61. In seriously ill patients (eg, those with sepsis, meningitis, removal of other foci of infection, an alternative to vancomycinpneumonia, or infective endocarditis) with suspected MRSA is recommended regardless of MIC.infection, a loading dose of 25–30 mg/kg (actual body weight) 70. 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 vancomycinone 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 anddose.) (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 issteady state conditions, prior to the fourth or ﬁfth dose. susceptible, in combination with another agent (e.g. gentamicinMonitoring of peak vancomycin concentrations is not 1 mg/kg IV every 8 h, rifampin 600 mg PO/IV daily orrecommended (B-II). Downloaded from cid.oxfordjournals.org by guest on February 6, 2011 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 daptomycintrough concentrations of 15–20 lg/mL are recommended are present, options may include the following: quinupristin-(B-II). 64. 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, orare adequate, and trough monitoring is not required (B-II). telavancin 10 mg/kg/dose IV once daily (C-III). These options 65. Trough vancomycin monitoring is recommended for may be given as a single agent or in combination with otherserious infections and patients who are morbidly obese, have antibiotics.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 treatmentrecommended (A-II). with mupirocin may be adequate in full-term neonates andPediatrics young infants (A-III). 75. For localized disease in a premature or very low- 67. Data are limited to guide vancomycin dosing in birthweight infant or more-extensive disease involving multiplechildren. IV vancomycin 15 mg/kg/dose every 6 h is sites in full-term infants, IV vancomycin or clindamycin isrecommended in children with serious or invasive disease recommended, at least initially, until bacteremia is excluded(B-III). (A-II). 68. The efﬁcacy and safety of targeting trough concentrationsof 15–20 lg/mL in children requires additional study but should Neonatal MRSA sepsisbe considered in those with serious infections, such as 76. IV vancomycin is recommended, dosing as outlined inbacteremia, infective endocarditis, osteomyelitis, meningitis, the Red Book (A-II) .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 94,360concentration (MIC) <2 lg/mL (eg, susceptible according to cases of invasive MRSA disease in the United States in 2005 .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 amonguse of vancomycin, independent of the MIC (A-III). previously healthy individuals in the community who lacked6 d CID 2011:52 (1 February) d Liu et al.
health care–associated risk factors . Unlike HA-MRSA, these PRACTICE GUIDELINESso-called CA-MRSA isolates are susceptible to many non–ß-lactam antibiotics. Furthermore, they are genetically distinct ‘‘Practice guidelines are systematically developed statements tofrom HA-MRSA isolates and contain a novel cassette element, assist practitioners and patients in making decisions about ap-SCCmec IV and exotoxin, Panton-Valentine leukocidin (PVL). propriate health care for speciﬁc clinical circumstances’’ .The epidemiology of MRSA has become increasingly complex as Attributes of good guidelines include validity, reliability, re-CA-MRSA and HA-MRSA strains have co-mingled both in the producibility, clinical applicability, clinical ﬂexibility, clarity,community and in health care facilities [7, 8]. Not unexpectedly, multidisciplinary process, review of evidence, and documenta-MRSA disease has had an enormous clinical and economic tion .impact [9, 10]. The wide spectrum of illness caused by MRSA includes SSTIs, METHODOLOGYbacteremia and endocarditis, pneumonia, bone and joint in- Panel Compositionfections, CNS disease, and toxic shock and sepsis syndromes. The IDSA Standards and Practice Guidelines CommitteeCA-MRSA was the most common cause of SSTI in a geo- (SPGC) convened adult and pediatric infectious diseases expertsgraphically diverse network of emergency departments in the in the management of patients with MRSA.United States ; however, there may be differences in localepidemiology to consider when implementing these guidelines. Literature Review and Analysis Downloaded from cid.oxfordjournals.org by guest on February 6, 2011SSTIs may range in clinical presentation from a simple abscess For the 2010 guidelines, the Expert Panel completed the reviewor cellulitis to deeper soft-tissue infections, such as pyomyositis, and analysis of data published since 1961. Computerized liter-necrotizing fasciitis, and mediastinitis as a complication of ret- ature searches of PUBMED of the English-language literatureropharyngeal abscess [12–15]. Bacteremia accompanies the were performed from 1961 through 2010 using the termsmajority (75%) of cases of invasive MRSA disease . A mul-titude of disease manifestations have been described, including, ‘‘methicillin-resistant Staphylococcus aureus’’ or ‘‘MRSA’’ andbut not limited to, infective endocarditis; myocardial, peri- focused on human studies but also included studies from ex-nephric, hepatic, and splenic abscesses; septic thrombophlebitis perimental animal models and in vitro data. A few abstractswith and without pulmonary emboli ; necrotizing pneu- from national meetings were included. There were few ran-monia [17–21]; osteomyelitis complicated by subperiosteal ab- domized, clinical trials; many recommendations were developedscesses; venous thrombosis and sustained bacteremia [16, 22, from observational studies or small case series, combined with23]; severe ocular infections, including endophthalmitis ;sepsis with purpura fulminans ; and Waterhouse-Frider- the opinion of expert panel members.ichsen syndrome . Process Overview The Expert Panel addressed the following clinical questions in In evaluating the evidence regarding the management of MRSA,the 2010 Guidelines: the Panel followed a process used in the development of other I. What is the management of SSTIs in the CA-MRSA era? IDSA guidelines. The process included a systematic weighting of II. What is the management of recurrent MRSA SSTIs? the quality of the evidence and the grade of recommendation III. What is the management of MRSA bacteremia and (Table 1) .infective endocarditis? IV. What is the management of MRSA pneumonia? Consensus Development Based on Evidence V. What is the management of MRSA bone and joint The Panel met on 7 occasions via teleconference to complete theinfections? work of the guideline and at the 2007 Annual Meeting of the VI. What is the management of MRSA infections of the CNS? IDSA and the 2008 Joint Interscience Conference on Antimi- VII. What is the role of adjunctive therapies for the treatment crobial Agents and Chemotherapy/IDSA Meeting. The purposeof MRSA infections? of these meetings was to discuss the questions to be addressed, to VIII. What are the recommendations for vancomycin dosing make writing assignments, and to deliberate on the recom-and monitoring? mendations. All members of the panel participated in the IX. How should results of vancomycin susceptibility testing be preparation and review of the draft guideline. Feedback fromused to guide therapy? external peer reviews was obtained. The guideline was reviewed X. What is the management of persistent MRSA bacteremia and endorsed by the Pediatric Infectious Diseases Society, theand vancomycin treatment failures? American College of Emergency Physicians, and American XI. What is the management of MRSA in neonates? Academy of Pediatrics. The guideline was reviewed and Clinical Practice Guidelines d CID 2011:52 (1 February) d 7
Table 1. Strength of Recommendation and Quality of EvidenceCategory/grade DeﬁnitionStrength of recommendationA 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 evidenceI 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 . Reproduced with the permission of the Minister of Public Works and Government Services Canada.approved by the IDSA SPGC and the IDSA Board of Directors recommended for detection of inducible clindamycin resistanceprior to dissemination. in erythromycin-resistant, clindamycin-susceptible isolates and is now readily available . Diarrhea is the most common Downloaded from cid.oxfordjournals.org by guest on February 6, 2011Guidelines and Conflict of Interest adverse effect and occurs in up to 20% of patients, and Clos-All members of the Expert Panel complied with the IDSA policy tridium difﬁcile–associated disease may occur more frequently,on conﬂicts of interest, which requires disclosure of any ﬁnancial compared with other oral agents. . The oral suspension isor other interest that might be construed as constituting an ac- often not well tolerated in children, although this may betual, potential, or apparent conﬂict. Members of the Expert Panel overcome with addition of ﬂavoring . It is pregnancy cate-were provided IDSA’s conﬂict of interest disclosure statement gory B .and were asked to identify ties to companies developing products Daptomycin. Daptomycin is a lipopeptide class antibioticthat might be affected by promulgation of the guideline. In- that disrupts cell membrane function via calcium-dependentformation was requested regarding employment, consultancies, binding, resulting in bactericidal activity in a concentration-de-stock ownership, honoraria, research funding, expert testimony, pendent fashion. It is FDA-approved for adults with S. aureusand membership on company advisory committees. The Panel bacteremia, right-sided infective endocarditis, and cSSTI. Itmade decisions on a case-by-case basis as to whether an in- should not be used for the treatment of non-hematogenousdividual’s role should be limited as a result of a conﬂict. Potential MRSA pneumonia, because its activity is inhibited by pulmonaryconﬂicts 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, theClindamycin. Clindamycin is approved by the US Food and lysylphosphatidyglycerol synthetase gene, are often present in suchDrug Administration (FDA) for the treatment of serious in- strains . 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 daptomycintreatment of MRSA infection, it has become widely used for MICs, suggesting possible cross-resistance [45, 47, 48]. Elevationstreatment of SSTI and has been successfully used for treatment in creatinine phosphokinase (CPK), which are rarely treatmentof invasive susceptible CA-MRSA infections in children, in- limiting, have occurred in patients receiving 6 mg/kg/day but notcluding osteomyelitis, septic arthritis, pneumonia, and lymph- in those receiving 4 mg/kg/day of daptomycin [49, 50]. Patientsadenitis [22, 29–31]. Because it is bacteriostatic, it is not should be observed for development of muscle pain or weaknessrecommended for endovascular infections, such as infective and have weekly CPK levels determined, with more frequentendocarditis or septic thrombophlebitis. Clindamycin has ex- monitoring in those with renal insufﬁciency or who are receivingcellent 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 . Therates of susceptibility to clindamycin are higher among CA- pharmacokinetics, safety, and efﬁcacy of daptomycin in childrenMRSA than they are among HA-MRSA , although there is have not been established and are under investigation .variation by geographic region [29, 36, 37]. The D-zone test is Daptomycin is pregnancy category B.8 d CID 2011:52 (1 February) d Liu et al.
Linezolid Linezolid is a synthetic oxazolidinone and in- Additional study is needed to deﬁne the role and optimal dosinghibits initiation of protein synthesis at the 50S ribosome. It is of rifampin in management of MRSA infections.FDA-approved for adults and children for the treatment of Telavancin. Telavancin is a parenteral lipoglycopeptideSSTI and nosocomial pneumonia due to MRSA. It has in vitro that inhibits cell wall synthesis by binding to peptidoglycanactivity against VISA and VRSA [53–55]. It has 100% oral chain precursors, causing cell membrane depolarization . Itbioavailability; hence, parenteral therapy should only be given if is bactericidal against MRSA, VISA, and VRSA. It is FDA-ap-there are problems with gastrointestinal absorption or if the proved for cSSTI in adults and is pregnancy category C. Cre-patient is unable to take oral medications. Linezolid resistance is atinine levels should be monitored, and dosage should berare, although an outbreak of linezolid-resistant MRSA infection adjusted on the basis of creatinine clearance, because nephro-has been described . Resistance typically occurs during toxicity was more commonly reported among individuals trea-prolonged use via a mutation in the 23S ribosomal RNA (rRNA) ted with telavancin than among those treated with vancomycinbinding site for linezolid  or cfr gene-mediated methylation in 2 clinical trials ; monitoring of serum levels is not avail-of adenosine at position 2503 in 23SrRNA [58, 59]. Long-term able.use is limited by hematologic toxicity, with thrombocytopenia Tetracyclines. Doxycycline is FDA-approved for theoccurring more frequently than anemia and neutropenia, pe- treatment of SSTI due to S. aureus, although not speciﬁcallyripheral and optic neuropathy, and lactic acidosis. Although for those caused by MRSA. Although tetracyclines have inmyelosuppression is generally reversible, peripheral and optic vitro activity, data on the use of tetracyclines for the treatmentneuropathy are not reversible or are only partially reversible of MRSA infections are limited. Tetracyclines appear to be Downloaded from cid.oxfordjournals.org by guest on February 6, 2011. Linezolid is a weak, nonselective, reversible inhibitor of effective in the treatment of SSTI, but data are lacking tomonoamine oxidase and has been associated with serotonin support their use in more-invasive infections . Tetracy-syndrome in patients taking concurrent selective serotonin- cline resistance in CA-MRSA isolates is primarily associatedreceptor inhibitors . Linezolid causes less bone marrow with tetK . Although the tet(M) gene confers resistance tosuppression in children than it causes in adults . The most all agents in the class, tet(K) confers resistance to tetracyclinecommon adverse events in children are diarrhea, vomiting, loose  and inducible resistance to doxycycline , with nostools, and nausea . The linezolid suspension may not be impact on minocycline susceptibility. Therefore, minocyclinetolerated because of taste and may not be available in some may be a potential alternative in such cases. Minocycline ispharmacies. It is considered pregnancy category C. available in oral and parenteral formulations. Tigecycline is Quinupristin-Dalfopristin. Quinupristin-dalfopristin is a glycylcycline, a derivative of the tetracyclines, and is FDA-a combination of 2 streptogramin antibiotics and inhibits protein approved in adults for cSSTIs and intraabdominal infections.synthesis. It is FDA-approved for cSSTI in adults and children .16 It has a large volume of distribution and achieves highyears of age. It has been used as salvage therapy for invasive MRSA concentrations in tissues and low concentrations in seruminfections in the setting of vancomycin treatment failure in adults (,1 lg/mL) . For this reason, and because it exhibitsand children [64–66]. Toxicity, including arthralgias, myalgias, bacteriostatic activity against MRSA, caution should be usednausea, and infusion-related reactions, has limited its use. Qui- in treating patients with bacteremia. The FDA recently issuednupristin-dalfopristin is considered pregnancy 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 mortalityreus and achieves high intracellular levels, in addition to pene- noted across phase III/IV clinical trials. Tetracyclinestrating bioﬁlms [67–69]. Because of the rapid development of are pregnancy category D and are not recommended forresistance, it should not be used as monotherapy but may be children ,8 years of age because of the potential for toothused 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 theinfections has not been deﬁnitively established, and there is treatment of any staphylococcal infections. However, becausea lack of adequately powered, controlled clinical studies in the 95%–100% of CA-MRSA strains are susceptible in vitro [81, 82],literature . The potential use of rifampin as adjunctive it has become an important option for the outpatient treatmenttherapy 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 andvariable throughout the literature, ranging from 600 mg daily in joint infections [86–88]. A few case reports  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 invasivedivided doses [70–74]. The range of rifampin dosing in these staphylococcal infections, such as bacteremia and endocarditisguidelines is suggested on the basis of the limited published data . TMP-SMX is effective for the treatment of purulent SSTIand is considered reasonable on the basis of expert opinion. in children . It has not been evaluated for the treatment of Clinical Practice Guidelines d CID 2011:52 (1 February) d 9
invasive CA-MRSA infections in children. Caution is advised 4. For outpatients with nonpurulent cellulitis (eg, cellulitiswhen using TMP-SMX to treat elderly patients, particularly with no purulent drainage or exudate and no associatedthose receiving concurrent inhibitors of the renin-angiotensin abscess), empirical therapy for infection due to b-hemolyticsystem and those with chronic renal insufﬁciency, because of an streptococci is recommended (A-II). The role of CA-MRSA isincreased risk of hyperkalemia . TMP-SMX is not recom- unknown. Empirical coverage for CA-MRSA is recommendedmended in pregnant women in the third trimester, when it is in patients who do not respond to b-lactam therapy and may beconsidered pregnancy category C/D, or in infants younger than considered in those with systemic toxicity. Five to 10 days of2 months of age. therapy is recommended but should be individualized on the Vancomycin. Vancomycin has been the mainstay of par- basis of the patient’s clinical response.enteral therapy for MRSA infections. However, its efﬁcacy has 5. For empirical coverage of CA-MRSA in outpatients withcome into question, with concerns over its slow bactericidal SSTI, oral antibiotic options include the following: clindamycinactivity, the emergence of resistant strains, and possible ‘‘MIC (A-II), TMP-SMX (A-II), a tetracycline (doxycycline orcreep’’ among susceptible strains [93–95]. Vancomycin kills minocycline) (A-II), and linezolid (A-II). If coverage for bothstaphylococci more slowly than do b-lactams in vitro, particu- b-hemolytic streptococci and CA-MRSA is desired, optionslarly at higher inocula (107–109 colony-forming units)  and include the following: clindamycin alone (A-II) or TMP-SMXis 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 Downloaded from cid.oxfordjournals.org by guest on February 6, 2011limited penetration into bone , lung epithelial lining ﬂuid therapy for the treatment of SSTI is not recommended (A-III). and CSF [104, 105]. Vancomycin is considered pregnancy 7. For hospitalized patients with complicated SSTI (cSSTI:category C . 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), linezolidMRSA 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). ASSTI 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 responseprimary treatment (A-II). For simple abscesses or boils, (A-II). Seven to 14 days of therapy is recommended but shouldincision 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 arein 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 ofsystemic illness, associated comorbidities or immunosuppres- Pediatric considerationssion, extremes of age, abscess in area difﬁcult to drain (eg, face,hand, and genitalia), associated septic phlebitis, lack of 9. For children with minor skin infections (such as impetigo) andresponse to I &D alone (A-III). secondarily infected skin lesions (such as eczema, ulcers, or 3. For outpatients with purulent cellulitis (eg, cellulitis lacerations), mupirocin 2% topical ointment can be used (A-III).associated with purulent drainage or exudate in the absence of 10. Tetracyclines should not be used in children ,8 years ofa drainable abscess), empirical therapy for CA-MRSA is age (A-II).recommended pending culture results. Empirical therapy for 11. In hospitalized children with cSSTI, vancomycin isinfection due to b-hemolytic streptococci is likely unnecessary recommended (A-II). If the patient is stable without ongoing(A-II). Five to 10 days of therapy is recommended but should bacteremia or intravascular infection, empirical therapy withbe individualized on the basis of the patient’s clinical clindamycin 10–13 mg/kg/dose IV every 6–8 h (to administerresponse. 40 mg/kg/day) is an option if the clindamycin resistance rate is10 d CID 2011:52 (1 February) d Liu et al.
low (eg, ,10%) with transition to oral therapy if the strain is development of resistance, rifampin should not be used assusceptible (A-II). Linezolid 600 mg PO/IV twice daily for monotherapy for the treatment of MRSA infections. The ad-children >12 years of age and 10 mg/kg/dose PO/IV every 8 h junctive use of rifampin with another active drug for the treat-for children ,12 years of age is an alternative (A-II). ment of SSTI is not recommended in the absence of data to support beneﬁt .Evidence Summary The need to include coverage against b-hemolytic strepto-The emergence of CA-MRSA has led to a dramatic increase in cocci in addition to CA-MRSA is controversial and may varyemergency department visits and hospital admissions for SSTIs depending on local epidemiology and the type of SSTI as dis-[106, 107]. For minor skin infections (such as impetigo) and cussed below. Although TMP-SMX, doxycycline, and minocy-secondarily infected skin lesions (such as eczema, ulcers, or cline have good in vitro activity against CA-MRSA, their activitylacerations), mupirocin 2% topical ointment may be effective. against b- hemolytic streptococci is not well-deﬁned [121–123].For cutaneous abscesses, the main treatment is incision and Clindamycin is active against b- hemolytic streptococci, al-drainage . For small furuncles, moist heat, which helps to though MRSA susceptibility rates may vary by region [85, 124,promote drainage, may be sufﬁcient . 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 inducibleditional beneﬁt, but incision and drainage is likely adequate for clindamycin resistance. The clinical signiﬁcance of induciblemost simple abscesses. Multiple, mostly observational studies clindamycin resistance is unclear because the drug may still beindicate high cure rates (85%–90%) whether or not an active effective for some patients with mild infections; however, its Downloaded from cid.oxfordjournals.org by guest on February 6, 2011antibiotic is used [11, 81, 110–112]. Two recently published presence should preclude the use of clindamycin for more-se-randomized clinical trials involving adult  and pediatric rious infections. 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 ofwas a suggestion that antibiotics may prevent the short-term a drainable abscess) should empirically receive oral antibioticsdevelopment of new lesions. Two retrospective studies suggest active against CA-MRSA while awaiting culture data. Amongimproved 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 thecurrently already underway will provide more-deﬁnitive answers dominant organism, isolated from 59% of patients, followed byto these questions. Antibiotic therapy is recommended for ab- MSSA (17%); b- hemolytic streptococci accounted for a muchscesses associated with the conditions listed in Table 2 [83, 116]. small proportion (2.6%) of these infections . 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 considereddamycin, and linezolid. Several observational studies [85, 117] to exclude occult abscess [126, 127]. For nonpurulent cellulitis,and one small randomized trial  suggest that TMP-SMX, the absence of culturable material presents an inherent challengedoxycycline, and minocycline are effective for such infections. to our ability to determine its microbiologic etiology and makeClindamycin 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 aspirationto less expensive alternatives . Because of the likely or punch biopsy cultures of nonpurulent cellulitis identiﬁed b-hemolytic streptococci and S. aureus as the main pathogens.Table 2. In the majority of cases, a bacterial etiology was not identiﬁed, but MSSA was the most common pathogen among those whoConditions in which Antimicrobial Therapy is Recommended afterIncision and Drainage of an Abscess due to Community-Associated were culture positive [128–133]. A retrospective case-controlMethicillin-Resistant Staphylococcus aureus study in children with nonpurulent cellulitis found that, com-Severe or extensive disease (eg, involving multiple sites of pared with b-lactams, clindamycin provided no additionalinfection) or rapid progression in presence of associated cellulitis beneﬁt, whereas TMP-SMX was associated with a slightly higherSigns and symptoms of systemic illness failure rate . The only prospective study of nonculturableAssociated comorbidities or immunosuppression (diabetes cellulitis among hospitalized inpatients found that b-hemolyticmellitus, human immunodeﬁciency virus infection/AIDS, neoplasm)Extremes of age streptococci (diagnosed by acute- and convalescent-phase se-Abscess in area difﬁcult to drain completely (eg, face, hand, rological testing for anti-streptolysin-O and anti-DNase-B an-and genitalia) tibodies or positive blood culture results) accounted for 73% ofAssociated septic phlebitis the cases; despite the lack of an identiﬁable etiology in 27% ofLack of response to incision and drainage alone cases, the overall clinical response rate to b-lactam therapy was Clinical Practice Guidelines d CID 2011:52 (1 February) d 11
12 dCID 2011:52 (1 February) 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 d abscess due to CA-MRSA.Liu et al. 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- 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 Linezolid 600 mg PO BID 10 mg/kg/dose PO every 8 h, not AII to exceed 600 mg/dose Downloaded from cid.oxfordjournals.org by guest on February 6, 2011
Table 3. (Continued) Manifestation Treatment Adult dose Pediatric dose Classa Comment 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 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 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/doseClinical Practice Guidelines 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 d PneumoniaCID 2011:52 (1 February) 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/ day13 d Downloaded from cid.oxfordjournals.org by guest on February 6, 2011