Infectious Diseases in Critical Care Medicine

resistance. There has been no clinically important resistance that has developed to any of the
anti-MRSA drugs except vancomycin (1,21,65–67). Additionally, there are concerns about
emerging resistance to daptomycin during therapy. Vancomycin therapy selects out
heteroresistant strains of MRSA that are relatively resistant to vancomycin. These isolates
are termed vancomycin intermediate susceptibleS. aureus(hVISA). These strains of hVISA are
relatively resistant to vancomycin and are difficult to detect with conventional susceptibility
testing. MRSA isolates with vancomycin minimum inhibitory concentrations (MICs) between 1
and 2mg/mL should be further tested to detect hVISA strains. Vancomycin resistance may be
mediated by staphylococcal cell wall thickening, which results in a “permeability-mediated”
resistance. Exposure to vancomycin over several days often results in thickened staphylococcal
cell walls. Thickened staphylococcal cell wall results in a “penetration barrier” to vancomycin
as well as other anti-staphylococcal antibiotics. Clinically, this is manifested as an increase in
MICs, which may represent either relative or high-level resistance. Strains of MRSA with
extremely high MICs are known as vancomycin-resistantS. aureus(VRSA) strains. Fortunately,
these MRSA isolates remain extremely rare. Because of the widespread use of vancomycin, cell

Table 6 Anti-MSSA and Anti-MRSA Antibiotics for Serious Systemic Infections (Continued)

Antibiotics/pathogens Attributes Disadvantages

S. aureus(MRSA)
Vancomycin l Lessactive against MSSA
than nafcillin
l Long experience
l Notnephrotoxic
l Drug fevers uncommon

l No oral formulation for bacteremia/SBE,

alternately use minocycline or linezolid

Quinupristin/

dalfopristin

l Useful for MSSA/MRSA

l Useful in rare cases of daptomycin-

resistant MSSA/MRSA

l Severe/prolonged myalgias

(rare, but serious)

l No oral formulation, alternately

use minocycline or linezolid

Linezolid l No hypersensitivity reactions

l Active against both MSSA/MRSA

l Bacteriostaticbut useful to treat

MSSA/MRSA ABE

l No dosage modification in CRF

l NoC. difficilepotential

l Relatively expensive

l Oral formulation (high bioavailability)

l Thrombocytopenia after>2wk

l Serotonin syndrome (rare)

Daptomycin l No dosage reduction in CRF

l For MSSA/MRSA bacteremias/

ABE use 6 mg/kg dose

l If bacteremia persists>72 hours

use “high-dose” (12 mg/kg)

daptomycin (well tolerated)

l Not nephrotoxic

l No hypersensitivity reactions

l NoC. difficilepotential

lFollowing vancomycin therapy,

resistance may occur during

therapy (rarely).

lNo oral formulation

lAlternately, use oral linezolid

or minocycline

Tigecycline lActive against MSSA/MRSA

lNo dosing modification in CRF

lNot nephrotoxic

lNo resistance potential

lHighly active againstC. difficile

(NoC. difficilepotential)

lNo oral formulation

lAlternately, use oral linezolid

or minocycline

Minocyclinea lAvailable IV/PO

lLimited experience, but useful for

MSSA/MRSA bacteremias/ABE

lInexpensive

lNo resistance potential

lNo.C. difficilepotential

lSkin discoloration (withprolonged use)

lEarly/mildtransient vestibular

symptoms (uncommon)

aFor CA-MRSA/CO-MRSA use minocycline instead of doxycline.

Abbreviations: MSSA, methicillin-sensitiveStaphylococcus aureus; MRSA, methicillin-resistantStaphylococcus
aureus; ABE, acute bacterial endocarditis; PCN, penicillin; CRF, chronic renal failure.
Source: Adapted from Ref. 1.

Antimicrobial Therapy of VRE and MRSA in Critical Care 507