Impact of Initial Vancomycin AUC over MIC on Treatment ......(VM) kills S. aureus with AUC 24h /MIC...
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Younghee Jung 1 , Shinhye Cheon 2 , Gayeon Kim 2 , Yu Min Kang 2 , Nak-Hyun Kim 2 , Ji-Whan Bang 2 , Eu Suk Kim 1,2 , Hong Bin Kim 1,2 , Sang-Won Park 2 , Nam Joong Kim 2 , Kyoung-Ho Song 1,2 and Myoung-don Oh 2 1 Seoul National University Bundang Hospital, 2 Seoul 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 (AUC 24h ) 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 AUC 24h was calculated using pharmacokinetic computer program based on the Bayesian approach and cutoff value of VM AUC 24h /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 (<431 and <398.5) initial VM AUC 24h /MIC (by E-test and BMD, respectively) showed higher treatment failure rate than cases with high (>431 and >398.5) initial VM AUC 24h /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 AUC 24h /MIC by E-test (<431) or BMD (<398.5) was independently associated with VM treatment failure (AOR 3.84, 95% CI, 1.17-12.38 in E-test, AOR 3.73, 95% CI, 1.10-12.61 in BMD). Conclusion: In MRSAB patients treated with VM, initial low VM AUC 24h /MIC by (<400-430) is an independent risk factor for treatment failure. Abstract Impact of Initial Vancomycin AUC 24h over MIC on Treatment Outcome in Methicillin-Resistant Staphylococcus aureus Bacteremia Several in vitro and animal studies showed that vancomycin (VM) kills S. aureus with AUC 24h /MIC dependent fashion. There are a few clinical studies on impact of VM AUC 24h /MIC, but they have limitations in determining AUC 24h because they did not consider inter-patient variability. Therefore, we aimed to study the impact of VM AUC 24h /MIC on treatment outcome in MRSA bacteremia by Bayesian approach for determining AUC 24h with individual VM serum concentration . Retrospective study in a single university-affiliated hospital with patients with MRSA bacteremia aged of ≥18 from July 2009 to January 2012. Exclusion criteria Dialysis, or duration of VM < 72 h or Without a serum VM level within 7 days of VM MIC test was performed by both E-test and broth microdilution test. AUC 24h was estimated by using the maximum a posteriori probability (MAP)-Bayesian approach (PKS, Abbott Pharmacokinetic System, version 1.10, Abbott Laboratories) Cutoff value of AUC 24h /MIC which differentiate best treatment failure and treatment success was performed by CART (Classification and Regression Tree) analysis. VM treatment failure was define as follows Persistent bacteremia (bacteremia 7 days after VM) or 30-day death Recurrence of MRSAB within 60 days after completion of therapy Complicated infection was defined as hematogenous seeding or extension of infection beyond the primary focus. Vancomycin treatment success (n = 56) Vancomycin treatment failure (n = 20) P Age ≥ 65 33 (58.9) 17 (85.0) 0.035 Gender (% of male) 42 (75.0) 16 (80.0) 0.652 Hospital-acquired 39 (69.6) 15 (75.0) 0.650 Healthcare-associated 12 (21.4) 2 (10.0) 0.331 Community-acquired 3 (5.4) 3 (15.0) 0.183 Charlson’s WIC (median) 2 (0-8) 1.5 (0-7) 0.183 Primary site of infection Catheter-related 23 (41.1) 4 (20.0) 0.091 Bone and joint 5 (8.9) 2 (10.0) 1 Skin and soft tissue 4 (7.1) 2 (10.0) 0.651 Surgical site 12 (21.4) 6 (30.0) 0.542 Lung 4 (7.1) 1 (5.0) 0.740 Infective endocarditis 0 (0) 1 (5.0) 0.263 Others 4 (7.1) 1 (5.0) 1 Unknown 4 (7.1) 3 (15.0) 0.371 Complicated infection 15 (26.8) 10 (50.0) 0.058 Pitt bacteremia score (median) 0.5 (0-7) 2.0 (0-6) 0.043 MIC ≥2 μg/mL by BMD 10 (17.9) 3 (15.0) 1 MIC ≥1.5 μg/mL by E-test 17 (30.4) 9 (45.0) 0.236 AUC 24h /MIC (BMD) <398.5 13 (23.2) 9 (45.0) 0.065 AUC 24h /MIC (E-test) <430 14 (25.0) 10 (50.0) 0.039 Risk factors Adjust OR (95% CI) Age ≥ 65 5.22 (1.23-22.14) Complicated infection 3.33 (1.04-10.70) AUC 24h /MIC by E-test <430 3.84 (1.17-12.38) Age ≥ 65 5.28 (1.22-22.91) Complicated infection 3.49 (1.09-11.21) AUC 24h /MIC by BMD <398.5 3.73 (1.10-12.61) MIC is not associated with VM treatment outcome. VM AUC 24h/ /MIC over 400-430 may improve treatment outcome in MRSA bacteremia, which is consist with previous in vitro and clinical studies . Of 132 patients with MRSA bacteremia, 76 patients were analyzed (6 patients transferred to other hospitals, 30 excluded due to dialysis, 14 treated VM <72h and 1 without VM level within 7 days of VM therapy). With CART analysis, the cut off value of initial steady state AUC 24h /MIC which best differentiated treatment success and treatment failure was 430 (by Etest) and 398.5 (by BMD). Table 1 Comparison of Characteristics Between Treatment Success and Treatment Failure Table 2 Significant Risk factors for VM Treatment Failure by Multivariate Logistic Regression Figure 1 Graph Presenting MIC and AUC 24h Red dots indicate VM treatment failure cases. Each blue bars indicate AUC 24h cutoff values which reach the cutoff value of AUC 24h /MIC under the given MIC (430 in E-test, 398.5 in BMD). Contact Information : Kyoung-Ho Song, MD Assistant Professor, Department of Internal Medicine, Seoul National University Bundang Hospital Tel +82-31-787-7044 Fax +82-31-787-4052 E-mail:[email protected] Background 1627 Results Methods Conclusion
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 (
