Impact of Initial Vancomycin AUC over MIC on Treatment ......(VM) kills S. aureus with AUC 24h /MIC...
Transcript of Impact of Initial Vancomycin AUC over MIC on Treatment ......(VM) kills S. aureus with AUC 24h /MIC...
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Younghee Jung1, Shinhye Cheon2, Gayeon Kim2, Yu Min Kang2, Nak-Hyun Kim2, Ji-Whan Bang2, Eu Suk Kim1,2, Hong Bin Kim1,2, Sang-Won Park2, Nam Joong Kim2 , Kyoung-Ho Song1,2 and Myoung-don Oh2
1Seoul National University Bundang Hospital, 2Seoul National University College of Medicine, South Korea
Background: There are few clinical studies about impact of
vancomycin (VM) area under the curve in 24 h (AUC24h) over
minimal inhibitory concentration (MIC) on treatment outcome
in Methicillin-Resistant Staphylococcus aureus (MRSA)
infections.
Methods: In patients with MRSA bacteremia (MRSAB), cases
who were initially treated with VM for at least 72 hours and
did not receive renal replacement therapy were enrolled from
1st Jul. 2009 to 31st Jan. 2012. MIC was determined by both
E-test and broth microdilution (BMD) test. The initial steady
state AUC24h was calculated using pharmacokinetic computer
program based on the Bayesian approach and cutoff value of
VM AUC24h/MIC for dividing VM treatment outcome was
calculated by Classification and Regression Tree (CART)
analysis.
Results: During the study period, total 76 patients were
analyzed. VM treatment failure (defined as persistent
bacteremia or 30-day mortality or recurrence of MRSAB) was
observed in 20 patients (26%) and 35 patients (46%) had
complicated infection (defined as hematogenous seeding or
extension of infection beyond the primary focus). The most
common infection focus was catheter-related infection (36%,
27/76) followed by skin and soft tissue infection (8%, 6/76)
and bone and joint infection (9%, 7/76). In univariate analysis,
decreased susceptibility to VM (MIC ≥1.5 μg/mL in E-test or
BMD) of MRSA isolates and high VM trough level (≥15 mg/L)
was not associated with treatment outcome. However, with
the use of CART analysis, cases with low (398.5) initial VM AUC24h/MIC (E-test: 50% vs.
25%; P = 0.039, BMD: 45% vs. 23%; P = 0.065). In
multivariate analysis, significant risk factors for treatment
failure were old age (≥65), complicated infection. In addition,
low initial VM AUC24h/MIC by E-test (