Early Appropriate Parenteral Antimicrobial Treatment of Complicated Skin and Soft Tissue Infections Caused by Methicillin-ResistantStaphylococcus aureus

Abstract

Background: Complicated skin and soft tissue infections (cSSTIs) are a major clinical problem, in part because of the increasing resistance of infecting bacteria to our current antibiotic therapies. Prompt appropriate treatment of infections in hospitalized patients reduces the mortality rate. Furthermore, appropriate and timely antibiotic therapy improves outcomes for cSSTIs caused by methicillin-resistant Staphylococcus aureus (MRSA). This review delineates factors to consider in the choice of initial antibiotic treatment for cSSTIs and describes the antimicrobial agents available or under clinical development for the treatment of cSSTIs caused by MRSA. Methods: Review of the pertinent literature and recommendations. Results: The choice of antimicrobial agent for empiric treatment of cSSTIs should be guided by the site and type of infection, the presence of an immunocompromised state or neutropenia, and risk factors for hospitalacquired MRSA (HA-MRSA) or community-associated MRSA (CA-MRSA) infection. Most CA-MRSA strains remain susceptible to ciprofloxacin, clindamycin, gentamicin, and trimethoprim/sulfamethoxazole, although resistance to clindamycin can emerge during treatment. Of the agents available for the treatment of HA-MRSA cSSTIs, vancomycin has been the reference standard, but clinical failures have been reported increasingly. Alternative agents for HA-MRSA include linezolid, which has been well-studied for treatment of cSSTIs, as well as daptomycin and tigecycline. A number of antibiotic agents are undergoing clinical trials or are under development for the treatment of cSSTIs caused by MRSA. Conclusions: Severe and progressive cSSTIs should be treated promptly with appropriate antibiotic agents. The choice of agent should be guided by a number of factors, including suspected CA-MRSA or HA-MRSA infection. Available agents should be evaluated carefully for efficacy in the treatment of MRSA cSSTIs.

Susceptibility of clinical methicillin-resistant Staphylococci isolates to new antibiotics

“…Fowler et alfound that S. aureus is more beneficial for right-sided endocarditis and bacteremia than the standard therapy; FDA approval was granted based on this study [54]. Daptomycin was reported to be effective in the treatment of skin and subcutaneous infections and blood infections caused by MRSA in many studies [12,31,35]. In the present study, 67% of MRSA strains were isolated from skin and soft tissue infections, and 12% were isolated from blood.…”

Integrated Analysis of CANVAS 1 and 2: Phase 3, Multicenter, Randomized, Double‐Blind Studies to Evaluate the Safety and Efficacy of Ceftaroline versus Vancomycin plus Aztreonam in Complicated Skin and Skin‐Structure Infection

“…these drugs can be limited by a narrow spectrum of activity, resistance, the need for monitoring of serum concentration, and/or adverse effects [11][12][13].…”

Prospective, Open-Label Investigation of the Pharmacokinetics of Daptomycin during Cardiopulmonary Bypass Surgery

“…First, this study is the first to examine a newer agent with broad-spectrum activity against Gram-positive organisms (including MRSA) and demonstrated that despite the swings in antibiotic concentration that occur during CPB, antibiotic concentrations appear sufficient to kill potential pathogens. Older antibiotics (e.g., trimethoprim-sulfamethoxazole, clindamycin, and doxycycline) that generally have activity against community-associated MRSA strains are not considered reliably active against circulating health care-acquired MRSA strains (28,36). Additionally, these older antibiotics (e.g., trimethoprim-sulfamethoxazole) have not been studied in the setting of CPB, hence their pharmacokinetics and appropriateness during CPB are unknown (20).…”