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Publication Date: July 2006
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LINEZOLID VS. VANCOMYCIN: AN
EVALUATION IN THE TREATMENT OF
SKIN AND SOFT TISSUE INFECTIONS
AND HOSPITAL-ACQUIRED PNEUMO-
NIA CAUSED BY METHICILLIN-
RESISTANT S A UREUS (MRSA)


Amy Bittle, Pharm.D. Candidate



Microbial resistance to antibiotics represents
one of the most common reasons for the failure to
cure an infection. Methicillin-resistant S. aureus
(MRSA), first detected after the introduction of me-
thicillin in the early 1960's, has emerged as the most
commonly identified antibiotic resistant pathogen in
hospitals across the United States.1 According to the
Centers for Disease Control and Prevention, the
prevalence of MRSA was 57% in US intensive care
units in 2002; this represents an increase of 30-40%
from the mid-1990s.2 MRSA is not strictly a nosoco-
mial pathogen; many genetically distinct strains have
now been identified in the community among healthy
patients without predisposing factors for MRSA ac-
quisition.1 The high incidence and continuously
growing rate of hospital-acquired (HA) MRSA and
now community-acquired (CA) MRSA is a major
threat and poses a difficult challenge for health-care
professionals.
MRSA is one of the leading pathogens found
in both nosocomial pneumonia and skin and soft tis-
sue infections (SSTIs).3 The prevalence of MRSA in
ventilator-associated pneumonia (VAP) constitutes
about 50% of the episodes caused by S. aureus.4
Hospital-acquired Pneumonia (HAP) is estimated to


account for almost half of infections found in the
ICU and approximately 60% of deaths from nosoco-
mial infections.5 Skin and soft tissue infections are
another significant cause of morbidity and mortality
in hospitals. Reports from the SENTRY Antimicro-
bial Surveillance Program reported a methicillin re-
sistance rate of 30% among S. aureus isolates in the
United States between 1997 and 1999 in skin and
soft tissue infections.6 Methicillin resistance in S.
aureus confers resistance to B-lactams, in addition to
macrolides, fluoroquinolones, tetracyclines, linco-
samides, and aminoglycosides. 3 Treatments effective
against MRSA include quinupristin/dalfopristin, dap-
tomycin, oritavancin, and tigecycline. Vancomcyin
has been the traditional drug used for nosocomial
pneumonia or complicated skin and soft tissue infec-
tions (cSSTIs) caused by gram-positive resistant or-
ganisms.3 Linezolid, an alternative agent, has gener-
ally been reserved for the treatment of serious infec-
tions due to its high cost and hematologic concerns.
The purpose of this paper is to compare the efficacy,
tolerability, and cost of vancomycin and linezolid in
the treatment of nosocomial pneumonia and skin and
soft tissue infections caused by MRSA.

rIa U I


am


SPharmaNote


VOLUME 21, ISSUE 10 JULY 2006
Lir


INSIDE THIS ISSUE:
Linezolid vs. Vancomycin: An Evaluation in the
Treatment of Skin and Soft Tissue Infections and
Hospital-Acquired Pneumonia Caused by
Methicillin-Resistant S. aureus (MRSA)



I*


Volume 21, Issue 10, July 2006


PharmaNote







Vancomycin
Vancomycin is a glycopeptide used to treat
serious infections caused by gram-positive bacteria.
After increasing resistance rates to oxacillin and the
introduction of MRSA, the use of vancomycin in
clinical practice skyrocketed.8 Vancomycin inhibits
cell wall synthesis by binding to the D-alanlyl-D-
alanine C-terminus of the nascent murein monomer,
inhibiting peptidoglycan synthesis.9 Vancomycin is
slowly bactericidal, with the degree of killing de-
pendent upon the time that the serum concentration
is above the organism's minimum inhibitory concen-
tration (MIC). Vancomycin does not exhibit a post-
antibiotic effect. In vitro studies demonstrate that
vancomycin exhibits slower bactericidal activity
compared to B-lactams in methicillin-susceptible S.
aureus.7 The concentration of vancomycin required
to inhibit most strains of S. aureus is typically be-
tween 0.5 and 2 mg/L. According to the Clinical and
Laboratory Standards Institute (CLSI), S. aureus iso-
lates with vancomycin MICs of 4 mg/L or less
should be considered susceptible, isolates with van-
comycin MICs between 8 and 16 mg/L are vancomy-
cin-intermediate, and isolates with vancomycin
MICs > 32 mg/L are considered vancomycin-
resistant.10 The emergence of S. aureus strains inter-
mediate or resistant to vancomycin has led to many
treatment failures.
Some pharmacokinetic properties of vanco-
mycin have contributed to its relatively high inci-
dence of treatment failure in VAP and SSTIs. Table
1 shows the clinical success rates of vancomycin in
various studies.11-14 Vancomycin has poor tissue
penetration, especially into the lungs.15 Concentra-
tions of vancomycin in the epithelial lining fluid
(ELF) do not reach 20% of the plasma concentra-
tion.16 In a study by Cruciani et al., an intravenous
(IV) infusion of 1 g of vancomycin over 1 h failed to


achieve sustained lung concentrations above the MIC
for susceptible S. aureus over a 12 h dosing inter-
val.17 The difficulties in obtaining adequate local se-
rum concentrations have led to higher doses and in-
tense pharmacokinetic monitoring to improve effi-
cacy and avoid toxicity. Studies have evaluated the
potential of higher trough concentrations of 15-20
mg/L to enhance efficacy with vancomycin. A con-
tinuous IV infusion of vancomycin has also been
studied. However, there is no clear consensus in the
literature supporting elevated trough concentrations
of 15-20 mg/L or continuous IV infusion. Higher
trough concentrations of vancomycin may increase
the risk of nephrotoxocity, particularly if the patient
is also receiving aminoglycosides.18
Vancomycin's high molecular weight con-
tributes to poor oral absorption. Therefore, vancomy-
cin must be administered IV for systemic infections.
IV access typically requires hospitalization and is
associated with additional resources and increased
costs. It also enhances the risk of phlebitis, puncture
accidents, as well as catheter-related and hospital-
acquired bloodstream. 3

Resistance
An emergence of staphylococci intermediate
or resistant to vancomycin has led to failures in noso-
comial pneumonia and SSTIs caused by MRSA. The
first clinical isolate of S. aureus with reduced suscep-
tibility to vancomycin was reported in 1997 from
Japan. These isolates were known as vancomycin-
intermediate S. aureus (VISA), also known as glyco-
peptide-intermediate S. aureus (GISA), since MICs
ranged from 8-16 mg/L.19 VISA strains produce an
excess amount of non-cross-linked D-alanyl-D-
alanine residues, which bind to vancomycin mole-
cules and sequester them. This prevents vancomycin
from reaching its target site, leading to treatment fail-


Table 1. Clinical success of vancomycin in MRSA nosocomial pneumonia
Trials N Dose Infection Success rate
Stevens et al 220 1 g vancomycin IV q 12 h HAP 53.8%

Fagon et a112 20 1 g vancomycin IV q 12 h HAP 40%

Wunderink et al13 54 1 g vancomycin IV q 12 h HAP 35.5%

Kollef et a114 91 1 g vancomycin IV q 12 h plus aztreonam VAP 21%

N = number of patients

PharmaNote 10 Volume 21, Issue 10, July 2006






ures. VISA strains also have a thicker cell wall with
increased amounts of peptidoglycan that further ob-
structs the movement of vancomycin molecules.19
Heteroresistant VISA (hVISA) also demonstrates
decreased susceptibility to vancomycin and is con-
sidered to be a precursor to VISA. hVISA is more
common, and now accounts for up to 26% of MRSA
isolates in Japan.8 Vancomycin MICs in hVISA are
in the susceptible range (< 4 mg/L); however sub-
populations have MICs > 4 mg/L exhibiting reduced
susceptibility. There are no standardized methods to
identify hVISA, which makes predicting treatment
failures difficult. Several published studies show
vancomycin to be ineffective for hVISA strains.8
Vancomycin-resistant S. aureus (VRSA) is rare and
is defined as an MIC > 32 mg/L. To date, there have
been 4 cases of VRSA. All cases have been in the
United States with each isolate from a single patient:
2 have been from Michigan, one from Pennsylvania,
and one from New York.10 VRSA strains obtain their
resistance by conjugal transfer of plasmids contain-
ing the vanA operon from vancomycin-resistant En-
terococcus faecalis.10 Common screening methods,
such as Vitek or Microscan, are not effective, with
about two-thirds of confirmed VRSA isolates not
reliably detected by automated testing systems.10
The development of resistance to vancomycin
in S. aureus has been associated with prolonged ex-
posure to low serum concentrations of the drug.20
Physicians tend to underdose vancomycin in patients
with renal failure.18 Moise et al. found a significant
association between decreased creatinine clearance
and vancomycin treatment failure.21 The majority of
cases of VISA have occurred in patients receiving
prolonged, suboptimal, or repeated courses of van-
comcyin or in patients receiving peritoneal or hemo-
dialysis.20 In addition, a polymorphism has been
identified among VISA and hVISA strains in the ac-
cessory gene regulator (agr). The agr operon in S.
aureus controls many virulence pathways. The agr
group II polymorphism was found to be an independ-
ent predictor of vancomycin failure in patients with
MRSA infection.21

Linezolid
Linezolid (Zyvox), an oxazolidinone, en-
tered the US market on April 18, 2000.22 Its ability to
target both susceptible and multi-drug resistant
strains makes it a highly effective agent to treat both
HAP and CAP, as well as SSTIs. Linezolid provides


inhibitory activity against most gram-positive cocci,
such as staphylococci, streptococci, and enterococci.
This includes resistant S. pneumoniae, staphylococci
resistant to methicillin, vancomycin, and B-lactam
antibiotics, and vancomycin-resistant enterococci
(VRE).23 In vitro studies show susceptible MICs for
staphylococci are between 0.5 and 4 mg/L.24 Line-
zolid is bacteriostatic for S. aureus. Unlike vancomy-
cin, it exhibits a post-antibiotic effect of 3-4 hours.15
Linezolid exerts its antimicrobial effects by prevent-
ing formation of the 70 S initiation complex of ri-
bosomes. Because of its mechanism of action, there
is virtually no cross-resistance between linezolid and
other classes of antibiotics (lincosamides, mac-
rolides, streptogramins, and chloramphenicol) affect-
ing ribosome mediated protein synthesis.23 Resis-
tance to linezolid is extremely rare. According to the
LEADER National Surveillance Study in 2004, all
2,872 isolated organisms of S. aureus showed sus-
ceptibility to linezolid. 25
The pharmacokinetics of linezolid give it an
advantage over vancomycin. Linezolid is 100%
bioavailable and can be administered both orally and
parentally. 3 Patients can transition to oral therapy-
with no dosage adjustments, which may facilitate
earlier discharge.23 Linezolid has excellent tissue
penetration. Protein binding with linezolid is 31%,
which provides free drug concentrations of > 40 mg/
L in the ELF.15 In Conti et al., following an IV or
oral dose, plasma concentrations were 15-20 mg/L,
while bronchoalveolar lavage concentrations (BLC)
exceeded 64 mg/L.26 Metabolism of linezolid is
through non-enzymatic oxidation of the morpholine
ring and is not dependent on hepatic enzyme action.
No dosage adjustments are necessary for patients
with hepatic or renal dysfunction.23
Linezolid appears to be safe and well toler-
ated in clinical trials. Common drug-related adverse
events include diarrhea, nausea, and headache, and
are typically of limited duration. Hematologic events
(anemia, thrombocytopenia, leukopenia, and neutro-
penia) have been reported; decreased platelet counts
are often associated with prolonged treatment
courses of more than 14 days. In phase III studies,
2.4% of patients treated with linezolid and 1.5% of
patients treated with comparator drugs developed
reversible thrombocytopenia.27 Other serious adverse
effects reported with linezolid include lactic acidosis,
pseudomembranous colitis, and peripheral and optic
neuropathy.23


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PharmaNote







Table 2: Clinical trial summaries
Infec-
Trial N Study Design tion Treatment Result

544 MN, R Analysis Linezolid 600 mg IV q 12 Linezolid had higher rates of clinical
Ko tal1N, (11Analysis
Kollef et a14 (91 of 2 DB, R VAP or vancomycin 1 g IV cure (62.2 vs 21.1%), survival
MRSA studies q 12 for 7-21 days plus (84.1% vs 61.1%) and eradication
cohort) aztreonam (60.5 vs 23%)

Vancomycin 1 g q 12 IV Response to treatment was higher in
Weigelt et a28 1,180 aLCCMN, cSSTI or linezolid 600 mg q 12 linezolid group (88%) compared to
PO or IV. vancomycin group (67%).

Linezolid 600 mg q 12 IV Linezolid was equal in efficacy and
Wunderink et a'13 396 RA, DB HAP or vancomycin 1 g q 12 tolerability compared to vancomy-
IV plus aztreonam for cin. Clinical cure rates (67.9%
7-21days vs 64.9%)

1,019 MN, R Analysis Vancomycin 1 g IV q 12 Clinical cure rates were higher with
(160 in
Wunderink et a129 (16 of 2 DB, Ra HAP or 600 mg linezolid IV linezolid (59% vs 35.5 %O), survival
S studies q 12 plus aztreonam analysis was 85% vs 67%
cohort)

R, OL M SST Vancomycin 1 g q 12 IV Microbiological success was 87%
Weigelt et al30 135 MC or linezolid 600 mg PO/ with linezolid vs 48% with vancom-
IV q 12 for 7-21 days cyin. (CI 16.51-60.27, p=0.002)

Ra=Randomized, DB=Double-blind, R=Retrospective, OL=Open-Label, CC-Comparator Controlled, MN=Multi-National, MC=Multi-Center

Clinical Trials adverse events in the study by Weigelt et al.28 Line-
Numerous head-to-head clinical trials have zolid and vancomycin reported similar drug-related
been conducted comparing the clinical efficacy of events. In the vancomycin arm, rash, phlebitis, ana-
linezolid and vancomycin to treat both HAP and phylaxis, and drug related allergic reactions were the
cSSTIs (table 2). Wunderink et al. evaluated 1,019 most common adverse effects, while gastrointestinal
patients with suspected nosocomial pneumonia (160 disturbances (nausea, diarrhea) and thrombocyto-
patients had documented MRSA pneumonia in the penia (3.5%) occurred more frequently in the line-
MRSA subset) and randomized them to receive ei- zolid group. No difference between the two groups
their 1 g of vancomycin every 12 h or 600 mg of line-
i-> iTable 3. Comparison of adverse events
zolid every 12 h, each with aztreonam. Clinical cure -- -------
rates with linezolid were 59% vs 35.5% treated with Linezolid Vancomycin
Adverse Events N=592 (%) N=588 (%)
vancomycin (p<0.01). Kaplan-Meier survival rates Serious Adverse 1(22.1)
were 85% for linezolid vs. 67% with vancomycin Events 131(22.1) 121(20.6)
(p=0.05).13 Weigelt et al. randomized 1,180 patients Drug-Related 2 (<) 8.4)
with suspected or proven MRSA infections to re- Events
ceive vancomycin 1 g every 12 h IV or linezolid 600 Most Common events (>1%)
mg every 12 h administered either orally or IV. The Anemia 7 (1.2) 10 (1.7)
primary outcome, defined as clinical response to Diarrhea 31(5.2) 9(1.5)
treatment, was significantly higher in the linezolid Headache 10 (1.7) 4 (0.7)
group (88.6%) compared to the vancomycin group Nausea 24 (4.1) 8 (1.4)
(66.9%) at the Test of Cure (TOC) visit for MRSA Pruritis 6 (1.0) 10 (1.7)
infections (p<0.001). 28 Rash 3 (0.5) 16 (2.7)
Thrombocyto- (3.5) 0
Adverse Effects penma
Vomiting 8 (1.4) 5 (0.9)
Table 3 lists the frequency of drug related Vomiting 8 (.4) 5(0.9)
N = number of events

PharmaNote Volume 21, Issue 10, July 2006







was observed in the frequency of adverse events
leading to drug discontinuation.28

Cost
Linezolid has been avoided due its high ex-
pense. The average retail cost of Zyvox surveyed
from three local pharmacies in Gainesville is $72.78
for one 600 mg tablet. For a 1 g vial of generic IV
vancomycin, the average retail cost from local phar-
macies is $15.39. However, clinical studies demon-
strate that linezolid is more cost effective in the long
run. The oral form of linezolid has led to decreased
costs versus the intravenous administration of vanco-
mycin. Shah et al. evaluated the direct cost of vanco-
mycin in MRSA infections. After including secon-
dary expenses (monitoring, drug administration, pro-
fessional involvement, and adverse events), each
dose of vancomycin generated an estimate increase
in cost between $23 and $43.31 Clinical trials with
oral linezolid have substantially decreased hospital
costs by reducing length of stay (LOS), reducing re-
sources associated with intravenous therapy, and fa-
cilitating earlier hospital discharges. Li et al., in a
phase III, open-label, comparator-controlled, multi-
center, multinational study, randomized 230 patients
to receive linezolid 600 mg twice a day vs 1 g vanco-
mycin IV twice a day for the treatment of cSSTIs.
LOS was shorter with linezolid than vancomycin (9
vs 14 days), and the estimated odds for hospital dis-
charge in the linezolid group was 1.87 times the esti-
mated odds of discharge in the vancomycin group.32
Sharpe et al. studied 60 patients requiring surgical
intervention for MRSA infected skin lesions. Patients
were randomized to receive oral linezolid 600 mg
every 12 h or 1 g vancomycin IV every 12 h for 7-21
days. LOS was 3 days shorter with linezolid and
saved $6,438 per patient in total hospital charges.
Outpatient charges with linezolid also resulted in a
savings of $388 per patient.33

Summary
Vancomycin has remained the drug of choice
for the treatment of MRSA, particularly in hospital-
acquired pneumonia, and skin and soft tissue infec-
tions. However, due to several parameters associated
with the pharmacokinetics of vancomycin, as well as
increasing prevalence of hVISA and VISA, treatment
failures have been observed. Linezolid, which is
available orally, is very effective in treating MRSA
intermediate or resistant to vancomycin. Clinical tri-


als show linezolid to have superior clinical out-
comes, increased cost effectiveness, and favorable
tolerability compared to vancomycin.

References
1. Deresinski S, et al. Methicillin-resistant Staphylococ-
cus aureus: an evolutionary, epidemiologic, and therapeu-
tic odyssey. Clinical Infectious Diseases 2005; 40:562-
73.
2. Tenover FC, Pearson, ML, et al. Methicillin-
resistance in Staphylococcus aureus. Emerg Infect Dis
2004; 10:2052-3.
3. Li, JZ, Wilke, RJ, Rittenhouse, BE, et al. Effect of
linezolid vs vancomycin on length of hospital stay in pa-
tients with complicated skin and soft tissue infections
caused by known or suspected methicillin-resistant
staphyloccoci: results from a randomized clinical trial.
Surgical Infections 2003; 4: 57-70.
4. Chastre J, Fagon JY, et al. Ventilator-associated
pneumonia. Am J Respir Crit Care Med 2002; 165:867-
903.
5. Soo Hoo GW, Wen EY, Nguyen TV, et al. Impact of
clinical guidelines in the management of severe hospital-
acquired pneumonia. Chest 2005; 128: 2778-2787.
6. Diekema, et al. Survey of infections due to Staphylo-
coccus species: frequency of occurrence and antimicro-
bial susceptability of isolates collected in the United
States, Canada, Latin America, Europe, and the Western
Pacific region for the Sentry Antimicrobial Surveillence
Program. 1997-1999. Clin Infect Dis 2001; 32:S114-32.
7. Jones RN, et al. Microbial features of vancomycin in
the 21st Century: minimum inhibitory concentration creep,
bacteriocidal/static activity, and applied breakpoints to
predict clinical outcomes or detect resistant strains.
Clinical Infectious Diseases 2006; 42: S13-24.
8. Levine, DP, et al. Vancomycin: A history. Clinical
Infectious Diseases 2006; 42: S5-12.
9. Kitzis MD, et al. Monitoring of vancomycin serum
levels for the treatment of staphylococcus infections.
European Society of Clinical Microbiology and Infectious
Diseases 2006; 12: 81-95.
10. Appelbaum PC, et al. The emergence of vancomy-
cin-intermediate and vancomycin-resistant Staphylococ-
cus aureus. Clin Microbiol Infect 2006; 12 (Suppl. 1):
16-23.
11. Stevens DL et al. Linezolid versus vancomycin forthe
treatment of methicillin-resistant Staphylococcus aureus
Infections. Clinical Infectious Diseases 2002; 34:1481-
1490.
12. Fagon J, Patrick H, Haas DW, et al. Treatment of
gram-positive nosocomial pneumonia: prospective ran-
domized comparison of quinupristin/dalfopristin versus
vancomycin. Nosocomial Pneumonia Group. Am J Respir
Crit Care Med 2000;161:753-762.
13. Wunderink RG, Kollef MH, Rello J, et al. Nosoco-


PharmaNote Volume 21, Issue 10, July 2006


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PharmaNote







mial pneumonia Staphylococcus aureus with methicillin-
resistant linezolid vs vancomycin: analysis of two double-
blind studies of patients. Chest 2003; 124: 1789-1797.
14. Kollef MN, et al. Clinical cure and survival in Gram-
positive ventilator-assisted pneumonia: retrospective
analysis of two double-blind studies comparing linezolid
with vancomycin. Intensive Care Med 2004; 30: 388-
394.
15. Stevens DL, et al. The role of vancomycin in the
treatment paradigm. Clinical Infectious Diseases. 2006;
42:S51-7.
16. Goldstein FW, Kitzis MD, et al. Vancomycin-
resistant Staphylococcus aureus: no apocalypse now. Clin
Microbiol Infect 2003;9:761-5.
17. Cruciani M, et al. Penetration of vancomycin into
human lung tissue. Journal of Antimicrobial Chemother-
apy 1996; 38: 865-869.
18. Guidelines for the management of adults with hospi-
tal-acquired, ventilator-associated, and healthcare-
associated pneumonia. The American Thoracic Society
Documents. Am J Respir Crit Care Med 2005; 171:388-
416.
19. Lam AP, Wunderink RG, et al. Methicillin Resistant
S. aureus Ventilator-associated pneumonia: strategies to
prevent and treat. Seminars in Respiratory and Critical
Care Medicine. 2006; 27(1): 92-103.
20. Ryback MJ, et al. The pharmacokinetic and pharma-
codynamic properties of vancomycin. Clinical Infectious
Diseases 2006; 42:S35-9.
21. Moise-Broder, Sakoulas G, Eliopoulos GM, et al. Ac-
cessory gene regulator group II polymorphism in methi-
cillin-resistant Staphylococcus aureus is predictive of fail-
ure of vancomycin therapy. Clinical Infectious Diseases
2004; 38:1700-5.
22. Plosker GL, Figgit DP, et al. Linezolid: A pharma-
coeconomic review of its use in serious gram positive
infections. Pharmacoeconomics 2005; 23 (9): 945-964.
23. Birmingham MC, Rayner CR, Meagker AK, et al.
Linezolid for the treatment of multidrug-resistant, gram-
positive infections: experience from a compassionate-use
program. Clinical Infectious Diseases 2003; 36:159-68.
24. Livermore DM, et al. Linezolid in vitro: mechanism
and antibacterial spectrum. J. Antimicrob Chemother
2003; 51: ii9-iil6.
25. Draghi DC, Sheehan DJ, Hogan P, Sahm DF, et al. In
vitro activity of linezolid against key gram-positive or-
ganisms isolated in the United States: results of the
LEADER 2004 Surveillance Program. J Antimicrob
Chemother 2005; 49 (12): 5024-32.
26. Conti JE, et al. Intrapulmonary pharmacokinetics of
linezolid. Antimicrob Agents Chemother 2002; 46: 1475-
80.
27. French G, et al. Safety and tolerability of Linezolid.
Journal of Antimicrobial Chemotherapy 2003; 51(S2):
ii45-ii53.


28. Weigelt J, Itani K, Stevens D, et al. Linezolid vs
vancomycin in treatment of complicated skin and soft
tissue infections. Antimicrobial Agents and
Chemotherapy 2005; 49 (6): 2260-2266.
29. Wunderink RG, Cammarata SK, Oliphant TH, et al.
Continuation of a randomized, double-blind, multicenter
study of linezolid versus vancomycin in the treatment of
patients with nosocomial pneumonia. Clin Ther 2003.
Mar;25(3):980-92.
30. Weigelt, J, Kaafarani H, Itani K, et al. Linezolid
eradicates MRSA better than vancomycin from surgical-
site infections. Am J Surg 2004; 44:3408-13.
31. Shah NP, Redd P, Paladino JA, et al. Direct medical
costs associated with using vancomycin in methicillin-
resistant Staphylococcus aureus infections: an economic
model. Current Medical Research and Opinion 2004;
20:779-90.
32. Li JZ, Wilke RJ, Rittenhouse BE, et al. Effect of line-
zolid vs vancomycin on length of hospital stay in patients
with complicated skin and soft tissue infections caused by
known or suspected methicillin-resistant Staphyloccoci:
Results from a randomized clinical trial. Surgical Infec-
tions 2003; 4: 57-70.
33. Sharpe, JN et al. Clinical and economic outcomes of
oral linezolid versus intravenous vancomycin in the treat-
ment of MRSA-complicated, lower extremity skin and
soft-tissue infections caused by methicillin-resistant
Staphylococcus aureus. Am J Surg 2005; 189: 425-428.




The PharmaNote is Published by:
The Department of Pharmacy
Services, UF Family Practice Medical
Group, Departments of Community
Health and Family Medicine and
Pharmacy Practice
University of Florida






John G. Gums
Pharm.D. Editor

R. Whit Curry, M.D. Associate Editor

Shawn D. Anderson, Assistant Editor
Pharm.D.


101 XWK W ^ S V ^ S W^V


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