considerations, for S. aureusisolates with an MIC > 1 mg/mL, vancomycin kills in a
concentration-dependent manner, but for isolates with an MIC<1 mg/mL, killing occurs in a
time-dependent fashion. Therefore, measuring vancomycin trough concentrations is clinically
irrelevant when MICs are<1 mg/mL (56–61).
Clinical Approach to Therapeutic Failure
Therapeutic failure manifested by fever or bacteremia that persists after a week of appropriate
therapy should prompt the clinician to reevaluate causes of antibiotic-related therapy. Also,
Table 10 Antibiotic Therapy of MSSA and MRSA Bacteremias (continued)
Antibiotics/
Pathogens Attribute Disadvantages
Clindamycin l Inexpensive
l MSSA excellent for infections (except
ABE)
l IV/PO formulations
l Low resistance potentiall Notactive against MRSA
l Notuseful for MSSA ABE
l HighC. difficilepotential
l Alternately, use oral linezolid or
minocyclineS. aureus(MRSA)
Vancomycin l Lessactive against MSSA than nafcillin
l Long experience
l Notnephrotoxic
l Permeability mediated resistance during/
after therapy (due to cell wall thickening)
l Nooralformulation forbacteremia/SBE
l NooralformulationQuinupristin/
dalfopristinl Useful for MSSA/MRSA
l Useful in cases of daptomycin-resistant
MSSA/MRSA (rare)l Severe/prolonged myalgias
l No oral formulation
l Leukopenia/thrombocytopenia
(uncommon)
Linezolid l No/low hypersensitivity potential
l Active against both MSSA/MRSA
l Bacteriostaticbut useful to treat MSSA/
MRSA ABE
l No dosage modification in CRF
l NoC. difficilepotentiall Relatively expensive
l Oral formulation (high bioavailability)
l Thrombocytopenia (after>2 wk)
l Serotonin syndrome (rare)Daptomycin l No dosage reduction in CRF (:dosing
interval)
l For MSSA/MRSA bacteremias/ABE use
6 mg/kg dose
l “If MRSA bacteremia persists>72 hr
use “high dose” (12 mg/kg) daptomycin
l Not nephrotoxic
l NoC. difficilepotentiall Following vancomycin therapy, resistance
may occur during therapy (rarely)
l No oral formulation
l Alternately, use oral linezolid or
minocyclineTigecycline l Active against MSSA/MRSA
l No dosing modification in CRF
l Not nephrotoxic
l No/low resistance potential
l NoC. difficilepotential
l Useful in PCN/sulfa allergyl No oral formulation
l Alternately, use oral linezolid or
minocyclineMinocycline l Available IV/PO
l Limited experience but useful for MSSA/
MRSA bacteremias/ABE
l Inexpensive
l No/low resistance potential
l NoC. difficilepotential
l No dosage modifications in CRFl Skin discoloration (only with prolonged
use)
l Early/mild transient vestibular symptoms
(uncommon)Abbreviations: ABE, acute bacterial endocarditis IV, intravenous; CRF, chronic renal failure; MRSA, methicillin-
resistantS. aureus; MSSA, methicillin-sensitiveS. aureus; PCN, penicillins.
Source: Adapted from Refs. 42 and 44.
214 Cunha