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 (