The Pharmacodynamics Optimization of Intermittent Vancomycin Dosage Regimens in Methicillin-Resistant Staphylococcus aureus Infections with MIC of 1.5 and 2.0 mg L in Thai Population - Ubaya Repository Eko Setiawan APCCMI

The Pharmacodynamics Optimiza
ization of Intermittent Vancomycin Dosage Regimens
ens in MethicillinResistant Staphylococcus aureus Infections
In
with MIC of 1.5 and 2.0 mg/L in Thai Pop
opulation
E Setiawan1,2*, P Montakantikul1, B Chindavijak1
1
Faculty of Pharmacy, Mahidol Univ
niversity, Bangkok, Thailand.
2
Faculty of Pharmacy, University of Surabaya, East Java, Indonesia.
Keywords: Vancomycin, Methicill
cillin-Resistant Staphylococcus aureus, Pharmacodyna
ynamics
Background
There are increasing number of artic
ticles questioning the efficacy of vancomycin to treat methicillin-resistant
me
Staphylococcus aureus (MRSA) with
ith MIC 1.5mg/L and 2.0mg/L. However, vancomycin

in iis still used as the
cornerstone treatment of MRSA infe
nfection particularly in most of developing countries with
ith limited alternative
MRSA coverage antibiotics. Owing
ng to the interest whether vancomycin still enable to bee uused as the cornerstone
treatment for MIC 1.5mg/L and 2mg
mg/L, present study was conducted to analyze the achiev
ievement of vancomycin
desired PK-PD indices in MRSA-inf
infected Thai population.
Methods
Monte Carlo simulation by using 10,000
10,
replications was performed for several vancomyc
ycin intermittent dosage
regimens ranging from 1g every 6,, 88, 12h, 1.5g and 2 g every 12h. Vancomycin concentra
trations were estimated
from population PK study conducted
ted in 212 Thai population. The probability of target atta

ttainment (PTA) of each
intermittent dosage regimen was calc
alculated from the number of simulated patients who ach
achieved AUC24/MIC
≥400 for MIC 1.5mg/L and 2.0mg/L
/L divided by total number of replication.
Results
Dosage regimen 1g every 12h couldn
ldn’t afford desired PTA for MRSA with MIC 1.5mg/L
/L and 2.0mg/L.
Considering the MRSA with MIC 1.5mg/L,
1.
dosage regimen 1g every 8h and 1.5g every 12h
12 could afford PTA
>80%. However, if particular condit
ditions required PTA >90%, dosage regimen 1g every 6 hours or 2g every 12h
should be recommended as the most
ost appropriate dosage regimen. While, for MRSA withh M
MIC 2.0mg/L, only
dosage regimens 4g/day, either given

ven as 1g every 6h or 2g every 12h, could afford PTA >8
>80%. No any dosage
regimens could afford PTA >90% fo
for MRSA with MIC 2.0mg/L. All PTA achievementt represented
re
the PTA at
steady state condition.
Conclusions
Intermittent dosage regimen at least
st 3g/day and 4g/day were needed to afford desired PTA
TA achievement for
MRSA with MIC 1.5mg/L and 2.0m
0mg/L, respectively. Finding of present study could bee uused as a guidance in
determining the best intermittent dos
dosage regimen in documented vancomycin treatment. Further
F
study was
needed to determine the most approp
ropriate intermittent dosage regimen that could achievee the
t desired PTA for

the 1st 24h.

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