Rationale:

• Moderate to severe MRSA infections may be associated with sepsis syndrome and limb-threatening infection. It is imperative to use antimicrobials for these infections that have been adequately tested in comparative trials.

Evidence:

• The listed antimicrobials have been compared to vancomycin, which is the gold standard, in the treatment of infections due to both MSSA and MRSA and are comparable (88; 100). However, a recent study reported more rapid resolution of clinical signs of inflammation in patients receiving daptomycin compared to a matched cohort of patients receiving vancomycin (101).
• Infections caused by community-acquired MRSA resulted in lower clinical success rates and more frequent recurrences than those caused by MSSA (102).

Comments:

• For less severe cellulitis or soft tissue infection, consider outpatient parenteral antibiotic therapy after a short observation period of several hours.
• Dalbavancin is an excellent choice for outpatient parenteral antibiotic therapy as its long half-life allows for once-weekly administration (103). Dalbavancin has shown a comparable efficacy to linezolid in the treatment of cellulitis and soft tissue infections (104; 105). However, the FDA has not yet approved this drug.
• Oritavancin is an investigational glycopeptide being studied for treatment of complicated skin and skin structure infections due to gram-positive bacteria (106).
• Linezolid, although more expensive than vancomycin, may permit earlier discharge from the hospital in view of its oral bioavailability (107; 108; 109; 110; 111; 112). A study of catheter-related bloodstream infections treated with linezolid vs. vancomycin, oxacillin, or dicloxacillin reported an increased risk of death for patients treated with linezolid (FDA Information for Healthcare Professionals: Linezolid (marketed as Zyvox)).
• In some studies, daptomycin has demonstrated an increased rate of resolution of some signs of inflammation compared to vancomycin (MRSA) and semisynthetic penicillins (MSSA) (113). However, other studies fail to show any difference in the rate of resolution of cellulitis among patients treated with daptomycin or vancomycin (114).
• Telavancin is a novel glycopeptide which inhibits peptidoglycan synthesis, disrupts the cell membrane, and alters membrane permeability (115). Given its multiple modes of action on MRSA, it may have a reduced potential for the development of resistance compared with other new antimicrobials active against MRSA. Telavancin was noninferior to vancomycin in a trial involving patients with complicated skin and skin-structure infections caused by MRSA (116).
• Ceftobiprole (117) and ceftaroline (118) are new cephalosporins that demonstrate activity against MRSA infections and gram-negative bacillary infections. Ceftobiprole was as effective as vancomycin plus ceftazidime in curing skin and skin-structure infections due to a variety of bacteria (119). In addition, they have a low potential for the selection of resistance in vitro (120).