therapy (1,10,26). While bactericidal drugs are preferable in the treatment of MRSA ABE,
linezolid and minocycline have been clinically as effective as bactericidal agents. MRSA bone
or joint infections are treated for four to six weeks or two weeks, respectively, with an IV/PO
anti-MRSA antibiotic (1,21). In addition to antimicrobial therapy, septic arthritis due to MRSA
requires joint aspiration/lavage. MRSA CNS shunt infections are treated primarily by VA/VP
shunt removal together with antimicrobial therapy that penetrates the CSF (1,21,62,63). The
anti-MRSA antibiotics that have excellent CNS penetration are linezolid and minocycline.
There is no evidence that “double drug” therapy to treat MRSA infections offers any advantage
over monotherapy. In particular, the addition of rifampin to an MRSA antibiotic does not
enhance anti-MRSA killing or improve outcomes and may be antagonistic (Table 6) (1,21,64).
Because of the relatively limited number of agents that are useful and detrimental against
MRSA, there is concern about the eventual loss of effectiveness of these agents due toTable 5 Factors in the Selection of Antimicrobial Therapy for Staphylococcal Bacteremias
l Select an antibiotic with known clinical efficacy and a high degree of activityagainst the presumed/known
pathogen, e.g., VSE, VRE, MSSA, or MRSA.
l If needed,adjust dosageto achieve therapeutic concentrations in serum/tissue.
l Select a “low-resistance” potential antibiotic, e.g., ertapenem, amikacin, minocycline, moxifloxacin,
levofloxacin, meropenem, tigecycline, and etc. Avoid “high-resistance” potential antibiotics, e.g., imipenem,
ciprofloxacin, gentamicin, tobramycin, and minimize the use of those that select out on resistant organisms,
e.g., vancomycin and ceftazidime
l Select an antibiotic with a favorable safety profileand a lowC. difficilepotential e.g., daptomycin, tigecycline,
linezolid, Q/D, minocycline.
l Select an antibiotic that is relatively cost-effective in the clinical context of bacteremia/endocarditis.
l If possible, select an oral antibiotic that is the same or equivalent to intravenous therapy for all/or part (IV?
PO switch) of the duration of antimicrobial therapy.Bactericidal antibiotics preferred for ABE.
Source: Adapted from Ref. 26.Table 6 Anti-MSSA and Anti-MRSA Antibiotics for Serious Systemic Infections
Antibiotics/pathogens Attributes Disadvantages
S. aureus(MSSA)
Nafcillin l Most activeanti-MSSA antibiotic
l The only anti-MSSA penicillin
with an enterohepatic circulation
l Inexpensive
l Long experience
l No dosing modification in CRF
l Low resistance potential
l NoC. difficilepotential
lShortt½requires frequent dosing
lDrug fevers (common)
lInterstitial nephritis (rare)
lNo oral formulation (avoid oral
anti-MSSA PCNs which are
notwell absorbed instead use oral
1st generation cephalosporin,
e.g., cephalexin)
Cefazolin l Most activeanti-MSSA
cephalosporin?clinical
effectiveness/outcomes*nafcillin
l Long experience
l Inexpensive
l Low resistance potential
l HighC. difficilepotentiallDrug fevers (common)
lAvoid in patients withanaphylactic
reactionsto PCN
lNo oral formulation (use oral
1st generation cephalosporin,
cephalexin)Ceftriaxone l Less anti-MSSA activity
than nafcillin or cefazolin
l Low resistance potential
l LowC. difficilepotentiallNo oral formulation (use oral
1st generation cephalosporin,
e.g., cephalexin)
lNon–C. difficilediarrhea (common)
Clindamycin l Inexpensive
l MSSA excellent for
infectionsexceptABE
l IV/PO formulations
l Low resistance potentiallNotactive against MRSA
lNotuseful for MSSA ABE
lC. difficile(common) alternately,
use oral linezolid or minocycline(Continued )506 Cunha