Key Points
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of both healthcare (HA-MRSA) and community-associated
(CA-MRSA) infections with an enormous clinical and economic impact. - MRSA causes a wide spectrum of illness including skin and soft tissue infections (SSTIs), bacteremia and endocarditis, pneumonia, bone and joint infections, central nervous system disease, toxic shock and sepsis syndromes.
- The management of all MRSA infections should include identification, elimination and/or debridement of the primary source and other sites of infection when possible (eg, drainage of abscesses, removal of central venous catheters, debridement of osteomyelitis, etc.).
- In patients with MRSA bacteremia, follow-up blood cultures 2-4 days
after initial positive cultures and as needed thereafter are recommended to document clearance of bacteremia. - To optimize serum trough concentrations in adult patients, vancomycin should be dosed according to actual body weight (15-20 mg/kg/dose every 8-12 hours), not to exceed 2 grams per dose.
- Trough monitoring is recommended to achieve target concentrations of 15-20 mcg/mL
in patients with serious MRSA infections and to ensure target concentrations in those who are morbidly obese, have renal dysfunction, or have fluctuating volumes of distribution. - The efficacy and safety of targeting higher trough concentrations in children requires further study but should be considered in those with severe sepsis or persistent bacteremia.
- When an alternative to vancomycin is being considered for use, in vitro susceptibility should be confirmed and documented in the medical record.
- For methicillin-sensitive S. aureus (MSSA) infections, a β-lactam antibiotic is the drug of choice in the absence of allergy.
Selecting a Treatment Regimen
Table 1. Recommendations for the Treatment of MRSA
| Manifestation | Treatments | Comments | ||||||
|---|---|---|---|---|---|---|---|---|
| Management/ Surgery | Duration of Therapy | Antibiotics | ||||||
| Agent (Brand) | Adult Dose | Pediatric Dose | Class (Adult/Child) | |||||
| Skin and Soft Tissue Infections (SSTI)* - Outpatients | ||||||||
| Minor skin infections (impetigo, secondarily infected skin lesions such as eczema, ulcers or lacerations) | Mupirocin 2% topical ointment | A-III | For simple abscesses or boils, incision and drainage is likely adequate, but additional data are needed to further define the role of antibiotics, if any, in this setting. Please refer to Appendix 1 for conditions in which antimicrobial therapy is recommended after incision and drainage of an abscess due to CA-MRSA. | |||||
| Abscesses, furuncles, carbuncles | Incision and drainage (I & D) | A-II | ||||||
| Purulent cellulitis (cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess) | Empiric therapy for CA-MRSA (A-II). No therapy for β-hemolytic streptococci (A-II). | Treat for 5-10 days.† | Clindamycin (Cleocin®, others) | 300-450 mg PO tid | 10-13 mg/kg/dose PO q6-8h Max: 40 mg/kg/day | A-II | Clostridium difficile-associated disease may occur more frequently compared to other oral agents. | |
| TMP-SMX‡ (Bactrim®) | 1-2 DS tab PO bid | Trimethoprim 4-6 mg/kg/dose, sulfamethoxazole 20-30 mg/kg/dose PO q12h | A-II | TMP-SMX‡ is pregnancy category C/D and not recommended for women in the third trimester of pregnancy and for children less than 2 months. | ||||
| Doxycycline | 100 mg PO bid | < 45 kg: 2 mg/kg/dose PO q12h > 45 kg: adult dose | A-II | Tetracyclines are not recommended for children under 8 years old (A-II) and are pregnancy category D. | ||||
| Minocycline (Minocin®) | 200 mg x 1, then 100 mg PO/IV bid | 4 mg/kg PO/IV x 1, then 2 mg/kg/dose PO/IV q12h | A-II | |||||
| Linezolid (Zyvox®) | 600 mg PO bid | 10 mg/kg/dose PO q8h Max: 600 mg/dose | A-II | More expensive compared to other alternatives. | ||||
| Non-purulent cellulitis (cellulitis with no purulent drainage or exudate and no associated abscess) | Empiric therapy for β-hemolytic streptococci (A-II) and for CA-MRSA in patients who fail to respond to β-lactam therapy or those with systemic toxicity. | Treat for 5-10 days.† | β-lactam (eg, cephalexin,‡ dicloxacillin) | 500 mg PO qid | Please refer to Red Book | A-II | For non-purulent cellulitis, empiric therapy for β-hemolytic streptococci is recommended (A-II). The role of CA-MRSA is unknown. Empiric coverage for CA-MRSA is recommended in patients who fail to respond to β-lactam therapy and may be considered in those with systemic toxicity. | |
| β-lactam (eg, amoxicillin‡) and TMP-SMX‡ (Bactrim®) or a tetracycline | Amox: 500 mg PO tid See above for TMP-SMX‡ and tetracycline dosing | Please refer to Red Book See above for TMP-SMX‡ and tetracycline dosing | A-II | Provide coverage for both β-hemolytic streptococci and CA-MRSA. | ||||
| Linezolid (Zyvox®) | 600 mg PO bid | 10 mg/kg/dose PO q8h Max: 600 mg/dose | A-II | |||||
| Clindamycin (Cleocin®, others) | 300-450 mg PO tid | 10-13 mg/kg/dose PO q6-8h Max: 40 mg/kg/day | A-II | |||||
| Skin and Soft Tissue Infections (SSTI)* - Inpatients | ||||||||
| Complicated SSTI (patients with deeper soft tissue infections, surgical/traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns) | Surgical debridement | Treat for 7-14 days.† | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | A-I/A-II | ||
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | A-I/A-II | For children ≥ 12 years, 600 mg PO/IV bid. Pregnancy category C. | ||||
| Daptomycin‡ (Cubicin®) | 4 mg/kg/dose IV daily | Ongoing study† | A-I/ND | The doses under study in children are 5 mg/kg (ages 12-17), 7 mg/kg (ages 7-11), 9 mg/kg (ages 2-6) (Clinicaltrials.gov NCT 00711802).† Pregnancy category B. | ||||
| Telavancin‡ (Vibativ®) | 10 mg/kg/dose IV daily | No data | A-I/ND | Pregnancy category C. | ||||
| Clindamycin (Cleocin®, others) | 600 mg PO/IV tid | 10-13 mg/kg/dose PO/IV q6-8h Max: 40 mg/kg/day | A-III/A-II | Pregnancy category B. | ||||
| Ceftaroline fosamil‡ (Teflaro®) was FDA approved for ABSSSI in adults caused by various susceptible pathogens including MRSA after the Guidelines were finalized. See Prescribing Information for dosing. | ||||||||
| Recurrent SSTI | Please see Management of Recurrent MRSA Skin and Soft Tissue Infections (page 12) | |||||||
| Pneumonia | ||||||||
| HA-MRSA or CA-MRSA pneumonia | Empiric MRSA therapy is recommended for severe community-acquired pneumonia pending culture results (A-III). Severe = ICU, necrotizing or cavitary infiltrates, or empyema. Empyema requires drainage (A-III). | Treat for 7-21 days.† | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | A-II | ||
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | A-II | For children ≥ 12 years, 600 mg PO/IV bid. Pregnancy category C. | ||||
| Clindamycin (Cleocin®, others) | 600 mg PO/IV tid | 10-13 mg/kg/dose PO/IV q6-8h Max: 40 mg/kg/day | B-III/A-II | Pregnancy category B. | ||||
| Bacteremia and Infective Endocarditis | ||||||||
| Bacteremia|| | A clinical assessment to identify the source and extent of the infection with elimination and/or debridement of other sites of infection should be conducted (A-II). Echocardiography is recommended for all adult patients with bacteremia. Transesophageal echocardiography (TEE) is preferred over transthoracic echocardiography (TTE). | Treat for 2-6 weeks.† | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | A-II | The addition of gentamicin‡ (A-II) or rifampin (A-I) to vancomycin‡§ is not routinely recommended. | |
| Daptomycin‡ (Cubicin®) | 6 mg/kg/dose IV daily | 6-10 mg/kg/dose IV daily | A-I/C-III | For adult patients, some experts recommend higher doses of 8-10 mg/kg/dose IV daily (B-III). Pregnancy category B. | ||||
| Persistent bacteremia | Please see Persistent MRSA Bacteremia and Vancomycin Treatment Failures in Adults (page 15) | |||||||
| Infective endocarditis, native valve | Repeat blood cultures 2-4 days after initial positive cultures and as needed thereafter are recommended to document clearance of bacteremia. | Treat for 6 weeks. | Same as for bacteremia | Evaluation for valve replacement surgery is recommended if large vegetation (> 10 mm in diameter), occurrence of ≥ 1 embolic events during the first two weeks of therapy, severe valvular insufficiency, valvular perforation or dehiscence, decompensated heart failure, perivalvular or myocardial abscess, new heart block, or persistent fevers or bacteremia (A-II). | ||||
| Infective endocarditis, prosthetic valve | Treat for ≥ 6 weeks plus gentamicin for 2 weeks. | Vancomycin‡§ and Gentamicin‡ and Rifampin | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-III | Early evaluation for valve replacement surgery is recommended (A-II). | ||
| 1 mg/kg/dose IV q8h | 1 mg/kg/dose IV q8h | |||||||
| 300 mg PO/IV q8h | 5 mg/kg/dose PO/IV q8h | |||||||
| Central Nervous System Infections | ||||||||
| Meningitis | For CNS shunt infection, shunt removal is recommended, and it should not be replaced until CSF cultures are repeatedly negative (A-II). | Treat for 2 weeks. | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-II | Some experts recommend the addition of rifampin 600 mg daily or 300-450 mg bid to vancomycin‡§ for adult patients (B-III). For children ≥ 12 years, linezolid 600 mg bid. | |
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | B-II | |||||
| TMP-SMX‡ (Bactrim®) | 5 mg/kg/dose PO/IV q8-12h | No data | C-III/ND | |||||
| Brain abscess, subdural empyema, spinal epidural abscess | Neurosurgical evaluation for incision and drainage is recommended (A-II). | Treat for 4-6 weeks. | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-II | Some experts recommend the addition of rifampin 600 mg daily or 300-450 mg bid to vancomycin‡§ for adult patients (B-III). For children ≥ 12 years, linezolid 600 mg bid. | |
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | B-II | |||||
| TMP-SMX‡ (Bactrim®) | 5 mg/kg/dose PO/IV q8-12h | No data | C-III/ND | |||||
| Septic thrombosis of cavernous or dural venous sinus | Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible (A-II). The role of anticoagulation is controversial. | Treat for 4-6 weeks. | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-II | Some experts recommend the addition of rifampin 600 mg daily or 300-450 mg bid to vancomycin‡§ for adult patients (B-III). For children ≥ 12 years, linezolid 600 mg bid. | |
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | B-II | |||||
| TMP-SMX‡ (Bactrim®) | 5 mg/kg/dose PO/IV q8-12h | No data | C-III/ND | |||||
| Bone and Joint Infections | ||||||||
| Osteomyelitis | Surgical debridement and drainage of associated soft tissue abscesses is the mainstay of therapy and should be performed whenever feasible (A-II). | Treat adults for ≥ 8 weeks (A-II); children for 4-6 weeks. If no debridement, continue for 12 weeks with rifampin plus 2nd drug based on sensitivities (C-III). | Vancomycin‡§ | 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-II/A-II | Some experts recommend the addition of rifampin 600 mg daily or 300-450 mg bid to the chosen antibiotic (B-III). For patients with concurrent bacteremia, rifampin should be added after clearance of bacteremia. For children ≥ 12 years, linezolid 600 mg PO/IV bid should be used. A single-strength and double-strength tablet of TMP-SMX‡ contains 80 mg and 160 mg of TMP, respectively. For an 80 kg adult, 2 DS tablets achieves a dose of 4 mg/kg. Magnetic resonance imaging (MRI) with gadolinium is the imaging modality of choice, particularly for detection of early osteomyelitis and associated soft tissue disease (A-II). Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) may be helpful to guide response to therapy (B-III). | |
| Daptomycin‡ (Cubicin®) | 6 mg/kg/day IV daily | 6-10 mg/kg/day IV daily | B-II/C-III | |||||
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | B-II/C-III | |||||
| Clindamycin (Cleocin®, others) | 600 mg PO/IV tid | If stable: 10-13 mg/kg/dose PO/IV q6-8h Max: 40 mg/kg/day | B-III/A-II | |||||
| TMP-SMX‡ (Bactrim®) and rifampin | 3.5-4 mg/kg/dose PO/IV bid 600 mg PO daily | No data | B-II/ND | |||||
| Septic arthritis | Drainage or debridement of the joint space should always be performed (A-II). | Treat for 3-4 weeks. | Vancomycinठ| 15-20 mg/kg/dose IV q8-12h | 15 mg/kg/dose IV q6h | B-II/A-II | ||
| Daptomycin‡ (Cubicin®) | 6 mg/kg/day IV daily | 6-10 mg/kg/dose IV daily | B-II/C-III | |||||
| Linezolid (Zyvox®) | 600 mg PO/IV bid | 10 mg/kg/dose PO/IV q8h Max: 600 mg/dose | B-II/C-III | |||||
| Clindamycin (Cleocin®, others) | 600 mg PO/IV tid | 10-13 mg/kg/dose PO/IV q6-8h Max: 40 mg/kg/day | B-III/A-II | |||||
| TMP-SMX‡ (Bactrim®) | 3.5-4 mg/kg/dose PO/IV bid | No data | B-III/ND | |||||
| Device-related Osteoarticular Infections | ||||||||
| Early-onset (< 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (≤ 3 weeks of symptoms), debridement but device retention | Parenteral therapy plus rifampin 600 mg daily or 300-450 mg twice daily for 2 weeks followed by rifampin plus a fluoroquinolone, TMP-SMX, a tetracycline or clindamycin for 3 months (hips) or 6 months (knees). | A-II | Long-term oral suppressive antibiotics (eg, TMP-SMX, a tetracycline, a fluoroquinolone,¶ or clindamycin) with or without rifampin may be considered in selected cases, particularly if device removal is not possible (B-III). For details please see antibiotic recommendations for device-related osteoarticular infections in full text guidelines at: http://www.idsociety.org/content.aspx?id=4432#mrsa | |||||
| Late-onset prosthetic joint infections, unstable implants or long duration (> 3 weeks) of symptoms | Antibiotic therapy in conjunction with prompt debridement with device removal. | A-II | ||||||
| Early-onset spinal implant infections (≤ 30 days after surgery), or implants in an actively infected site | Parenteral therapy plus rifampin followed by prolonged oral therapy is recommended. The optimal duration of parenteral and oral therapy is unclear; the latter should be continued until spine fusion has occurred. For late-onset infections (> 30 days after implant placement), device removal whenever feasible is recommended. | A-II | ||||||
| Late-onset spinal implant infections (> 30 days after surgery) | Antibiotic therapy in conjunction with device removal whenever feasible is recommended. | A-II | ||||||
| NOTE: The use of rifampin as a single agent or as adjunctive therapy for the treatment of SSTI is NOT recommended (A-III). * Cultures from abscesses and other purulent SSTI are recommended in patients treated with antibiotic therapy, those with severe local infection or signs of systemic illness, patients who have not responded adequately to initial treatment, and if there is concern for a cluster or outbreak (A-III). ‡ Adjust dose for renal impairment – see Prescribing Information for renal dosing. § Max: 2 gm/dose. In seriously ill patients consider a loading dose of 25-30 mg/kg (C-III). ¶ Due to the potential emergence of fluoroquinolone resistance, particularly if adequate surgical debridement is not possible, it should be given in conjunction with rifampin. † Based on the extent of disease and the patient’s clinical response. || Repeat blood cultures 2-4 days after initial positive cultures and as needed thereafter are recommended to document clearance of bacteremia (A-II). | ||||||||
Appendix 1. Conditions in which Antimicrobial Therapy is Recommended After Incision and Drainage of an Abscess Due to CA-MRSA
- Severe or extensive disease (eg, multiple sites) or rapid progression in presence of associated cellulitis
- Signs and symptoms of systemic illness
- Associated comorbidities or immunosuppression (diabetes mellitus, HIV/AIDS, neoplasm)
- Extremes of age
- Abscess in area difficult to drain completely (eg, face, hand, genitalia)
- Associated septic phlebitis
- Lack of response to incision and drainage alone
Management of Recurrent MRSA Skin and Soft Tissue Infections
- Preventive educational messages on personal hygiene and appropriate wound care are recommended for all patients with SSTI. Instructions should be provided to:
- Keep draining wounds covered with clean, dry bandages (A-III).
- Maintain good personal hygiene with regular bathing and cleaning of hands with soap and water or an alcohol-based hand gel, particularly after touching infected skin or item that has directly contacted a draining wound (A-III).
- Avoid reusing or sharing personal items (eg, razors, linens and towels) that have contacted infected skin (A-III).
- Environmental hygiene measures should be considered in patients with recurrent SSTI in the household/community setting:
- Focus cleaning efforts on high-touch surfaces that may contact bare skin or uncovered infections (C-III).
- Commercially available cleaners or detergents appropriate for the surface being cleaned should be used according to label instructions for routine cleaning of surfaces (C-III).
- Decolonization may be considered in selected cases if:
- A patient develops a recurrent SSTI despite optimizing wound care and hygiene measures (C-III).
- Ongoing transmission is occurring among household members or other close contacts despite optimizing wound care and hygiene measures (C-III).
- Decolonization strategies should be offered in conjunction with ongoing reinforcement of hygiene measures and may include:
- Nasal decolonization with mupirocin twice daily for 5-10 days (C-III).
- Nasal decolonization with mupirocin twice daily for 5-10 days and topical body decolonization regimens with a skin antiseptic solution (eg, chlorhexidine) for 5-14 days or dilute bleach baths (1 teaspoon per gallon of water or 1/4 cup per 1/4 bathtub [or 13 gallons of water] given for 15 minutes twice weekly for ~3 months can be considered) (C-III).
- Oral antimicrobial therapy is recommended for the treatment of active infection only and is not routinely recommended for decolonization (A-III). An oral agent in combination with rifampin, if susceptible, may be considered for decolonization if infections recur despite above measures (C-III).
- In cases where household or interpersonal transmission is suspected:
- Personal and environmental hygiene measures in the patient and contacts are recommended (A-III).
- Contacts should be evaluated for evidence of S. aureus infection:
- Symptomatic contacts should be evaluated and treated (A-III); nasal and topical body decolonization strategies may be considered following treatment of active infection (C-III).
- Nasal and topical body decolonization of asymptomatic household contacts may be considered (C-III).
- The role of cultures in the management of patients with recurrent SSTI is limited:
- Screening cultures prior to decolonization are NOT routinely recommended if at least one of the prior infections was documented as MRSA (B-III).
- Surveillance cultures following a decolonization regimen are NOT routinely recommended in the absence of an active infection (B-III).
MRSA Infections in Neonates
Neonatal pustulosis
- For mild cases with localized disease, topical treatment with mupirocin may be adequate in full-term neonates and young infants (A-III).
- For localized disease in a premature or very low birthweight infant or more extensive disease involving multiple sites in full-term infants, IV vancomycin or clindamycin is recommended at least initially until bacteremia is excluded (A-II).
Neonatal MRSA sepsis
- IV vancomycin is recommended, dosing as outlined in the Red Book (A-II).
- Clindamycin and linezolid are alternatives for non-endovascular infections (B-II).
Vancomycin Monitoring
- Trough vancomycin concentrations are the most accurate and practical method to guide vancomycin dosing (B-II). Serum trough concentrations should be obtained at steady state conditions, prior to the fourth or fifth dose. Monitoring of peak vancomycin concentrations is not recommended (B-II).
- For serious infections such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, and severe SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin trough concentrations of
15-20 mcg/mL are recommended (B-II). - For most patients with SSTI who have normal renal function and are not obese, traditional doses of 1 gram every 12 hours are adequate and trough monitoring is not required (B-II).
- Trough vancomycin monitoring is recommended for serious infections and patients who are morbidly obese, have renal dysfunction including those on dialysis, or have fluctuating volumes of distribution (A-II).
- Continuous infusion vancomycin regimens are not recommended (A-II).
- The efficacy and safety of targeting trough concentrations of
15-20 mcg/mL in children requires further study but should be considered in those with serious infections such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, and severe SSTI (ie, necrotizing fasciitis) (B-III).
Vancomycin Susceptibility Testing
- There is considerable variability in MIC results depending on the method used. One challenge is that acceptable variability for MIC methods is /- one doubling dilution making it difficult to distinguish between a MIC of 1 vs. 2 mcg/mL.
- Etest, MicroScan, and BD-Phoenix report higher MIC values than reference broth microdilution, overcalling susceptible strains as intermediate in some cases while the Sensititre and Vitek 2 systems tend to undercall resistance.
- As current susceptibility testing methods are unable to reliably distinguish between MICs of 1 mcg/mL from 2 mcg/mL and vice versa, the patient’s clinical and microbiologic response should be evaluated along with MIC results when making decisions regarding therapy.
- For isolates with a vancomycin MIC ≤ 2, eg, “susceptible” according to CLSI breakpoints, the patient’s clinical response should determine the continued use of vancomycin, independent of the MIC (A-III).
- If the patient has had a clinical and microbiologic response to vancomycin, then it may be continued with close follow-up
- If the patient has not had a clinical or microbiologic response to vancomycin despite adequate debridement and removal of other foci of infection, an alternative to vancomycin is recommended regardless of MIC.
- For isolates with a vancomycin MIC > 2 mcg/mL, eg, vancomycin-intermediate S. aureus (VISA) or vancomycin-resistant S. aureus (VRSA), an alternative to vancomycin should be used (A-III).
Persistent MRSA Bacteremia and Vancomycin Treatment Failures in Adults
- A search for and removal of other foci of infection, drainage or surgical debridement is recommended (A-III).
- High-dose daptomycin, if the isolate is susceptible, in combination with other agents should be considered (B-III).
- Please see antibiotic recommendations in full text guidelines for details at
http://www.idsociety.org/content.aspx?id=4432#mrsa
- Please see antibiotic recommendations in full text guidelines for details at
- If reduced susceptibility to vancomycin and daptomycin are present, options may include: quinupristin-dalfopristin 7.5 mg/kg/dose IV every 8 hours, trimethoprim/sulfamethoxazole 5 mg/kg/dose IV twice daily, linezolid 600 mg PO/IV twice daily, or telavancin 10 mg/kg/dose
IV once daily (C-III).
These options may be given as a single agent or in combination with other antibiotics.