Medication Summary
Historically, isolates resistant to oxacillin (commonly referred to as MRSA) were resistant to most agents other than vancomycin, but these isolates were limited to nosocomial infections. In the 1990s, many reports appeared describing community-acquired MRSA infections that were susceptible to various non–beta-lactam antibiotics. As such, patients with serious staphylococcal infections should be initially started on agents active against MRSA until susceptibility results are available. [39, 40, 41] Many CoNS are oxacillin-resistant. The duration of treatment depends on the type of infection encountered. Treatment of methicillin-susceptible S aureus (MSSA) bacteremia with cefazolin has been shown to improve survival rates and decrease toxicity in comparison to antistaphylococcal penicillins. [42, 43] S aureus endocarditis may require a prolonged course of antibiotics, although recent studies suggest it may be possible to switch many patients with endocarditis or complicated bacteremia to oral therapy after an initial course of 10 to 14 days of IV antimicrobial therapy. [44, 45, 46, 47]
Although many strains of MRSA that cause community-acquired infection are susceptible to trimethoprim-sulfamethoxazole, treatment with trimethoprim-sulfamethoxazole has been associated with clinical failure, especially in the presence of significant tissue damage. [48] Clindamycin decreased the repeat infection rate in one study of patients receiving incision and drainage for small skin abscesses compared with placebo trimethoprim-sulfamethoxazole. [49]
Vancomycin-resistant isolates have been reported; isolates with an increased minimum inhibitory concentration (MIC) to vancomycin are becoming more common and include both MRSA and MSSA. [50] Consensus guidelines no longer recommend dosing vancomycin based on trough levels of 15-20 mcg/mL, [51] but instead recommend dosing vancomycin based on the area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC) with a target of 400-600 mg*hour/L. [52] .The results of such testing are often delayed .Because of these drawbacks and the availability of less nephrotoxic and more effective alternatives , vancomycin has a very limited role in treating staphylococcal infections. [53, 46]
In a study of 296 consecutive MRSA bacteremia episodes, several factors were predictive of high vancomycin MIC, including age older than 50 years, prior vancomycin exposure, history of MRSA bacteremia, history of chronic liver disease, and presence of a nontunneled catheter. [54]
In a small study (40 subjects) with MRSA bacteremia, the combination of ceftaroline plus daptomycin was found to have lower in-hospital mortality rate as compared to vancomycin or daptomycin monotherapy. [55] The addition of daptomycin to cefazolin or cloxacillin did not result in improved outcomes in patients with MSSA bacteremia. [56]
Antibiotics
Class Summary
Empiric antimicrobial therapy should be comprehensive and cover all likely pathogens in the context of the clinical setting.
Cefazolin
First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including S aureus (MSSA). Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar.
Ceftaroline (Teflaro)
Fifth-generation cephalosporin antimicrobial with activity against aerobic gram-negative bacteria, anaerobic gram-positive bacteria, and aerobic gram-positive bacteria, including MRSA.
Cefuroxime (Ceftin, Zinacef)
Second-generation cephalosporin with activity against respiratory aerobic gram-negative organisms, including Haemophilus influenza, and aerobic gram-positive aerobic organisms, including Streptococcus pyogenes and MSSA.
Dicloxacillin (Dycill, Dynapen)
Binds to one or more penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. For treatment of infections caused by penicillinase-producing staphylococci susceptible to methicillin (MSSA). Also active against most nonenterococcal streptococci. May use to initiate therapy when staphylococcal infection is suggested.
Nafcillin (Nallpen in Dextrose)
Preferred therapy for methicillin-susceptible S aureus (MSSA) staphylococci infections. Use parenteral therapy initially in severe infections. Oxacillin may be substituted for nafcillin based on hospital formulary. Change to oral therapy as condition warrants.
Dalbavancin (Dalvance)
Dalbavancin is a lipoglycopeptide antibiotic that prevents cross-linking by interfering with cell wall synthesis. It is bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations observed in humans at recommended doses. It is indicated for treatment of acute bacterial skin and skin structure infections caused by gram-positive bacteria including S aureus (including MSSA and MRSA ), S pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S anginosus, S intermedius, S constellatus).
Oritavancin (Orbactiv)
Oritavancin is lipoglycopeptide antibiotic that inhibits cell wall biosynthesis and disrupts bacterial membrane integrity that leads to cell death. It is indicated for treatment of acute bacterial skin and skin structure infections caused by gram-positive bacteria including S aureus (including methicillin-susceptible S aureus and MRSA), S pyogenes, S agalactiae, S dysgalactiae, S anginosus group (S anginosus, S intermedius, S constellatus) and E faecalis (vancomycin-susceptible isolates only).
Telavancin (Vibativ)
Lipoglycopeptide antibiotic that is a synthetic derivative of vancomycin. Inhibits bacterial cell wall synthesis by interfering with polymerization and cross-linking of peptidoglycan. Unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity. Indicated for complicated skin and skin structure infections caused by susceptible gram-positive bacteria, including Staphylococcus aureus (both methicillin-resistant and methicillin-susceptible strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis (vancomycin-susceptible isolates only).
Linezolid (Zyvox)
Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against staphylococci (MSSA/MRSA).
The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.
Vancomycin
Its role is quite limited because of difficulty I achieving adequate levels and the availability safer and more effective antibiotics
Tedizolid (Sivextro)
Tedizolid is an oxazolidinone antibiotic indicated for skin and skin structure infections caused by susceptible isolates of Gram-positive bacteria including Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, S agalactiae, S anginosus Group (including S anginosus, S intermedius, and S constellatus), and Enterococcus faecalis. Its action is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis.
Doxycycline (Acticlate, Adoxa, Vibramycin, Doryx)
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Active against MSSA/MRSA. Less active against coagulase-negative staphylococci.
Minocycline (Minocin, Solodyn)
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Active against MSSA/MRSA. Less active against coagulase-negative staphylococci. Doxycycline (Vibramycin) is used more commonly than minocycline.
Clindamycin (Cleocin)
Lincosamide for treatment of serious skin and soft tissue staphylococci infections. Also effective against aerobic and anaerobic streptococci (except enterococcal). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Daptomycin (Cubicin)
Indicated to treat complicated skin and skin structure infections caused by S aureus (including MRSA strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, and Enterococcus faecalis. Also indicated for right-sided endocarditis due to S aureus. First of new antibiotic class called cyclic lipopeptides. Binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis and ultimately causing cell death.
Quinupristin/dalfopristin (Synercid)
Belongs to the streptogramin group of antibiotics. Mechanism of action is similar to macrolides/lincosamides. Inhibits protein synthesis and is usually bacteriostatic. Also an option for methicillin-resistant S aureus (MRSA) infections.
Tigecycline (Tygacil)
A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit, and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections and complicated intra-abdominal infections. Active against S aureus (including MRSA), as well as most streptococci, enterococci (including VRE), and gram-negative organisms (including anaerobes).
Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Sulfatrim Pediatric)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Active against most staphylococci (MSSA), including some strains resistant to methicillin (MRSA).
Delafloxacin (Baxdela)
New oral and intravenous fluoroquinolone with activity against MRSA. The best of this class for MRSA, although not a preferred agent, as it is new and quite expensive.
- Embolic lesions in patient with Staphylococcus aureus endocarditis.
- Close-up view of embolic lesions in patient with Staphylococcus aureus endocarditis.
- Fifty-six-year-old man with erythema, edema, and drainage from below his right eye.
- Gram stain in a 70-year-old woman with rheumatoid arthritis.
