Evaluation of Vancomycin Population Susceptibility Analysis Profile as a Predictor of Outcomes for Patients with Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACTInfective endocarditis due to methicillin-resistantStaphylococcus aureus(MRSA IE) is associated with high morbidity and mortality. Vancomycin continues to be the primary treatment for this disease. The emergence of heterogeneous vancomycin-intermediateStaphylococcus aureus(hVISA), defined as a modified population analysis profile (PAP) of ≥0.9, may affect patient outcomes. The objective of this study was to evaluate the relationship of vancomycin subpopulation susceptibility and the clinical outcomes of MRSA IE. We conducted a retrospective cohort study of patients treated with vancomycin for MRSA IE from 2002 to 2013 at the Detroit Medical Center. A modified PAP was used to measure the vancomycin PAP MIC and the PAP-to-area under the curve (AUC) ratio. Treatment failure was defined as bacteremia for ≥7 days or death attributed to MRSA. Classification and regression tree (CART) analysis was used to select a failure breakpoint between the PAP-AUC ratios and the PAP MIC. A total of 202 patients were included in the study. Twenty-seven percent of the patients had left-sided IE, 19% of the strains were hVISA, and 70% of the strains were staphylococcal cassette chromosomemecelement (SCCmec) type IV. Overall treatment failure was observed in 64%; 59% had persistent bacteremia, and the 30-day attributable mortality rate was 21%. The CART breakpoint between failure and success in terms of the PAP-AUC ratio was 0.9035. On logistic regression analysis, intensive care unit (ICU) admission (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.5 to 5.2) and a PAP MIC of ≥4 mg/liter (aOR, 3.2; 95% CI, 1.3 to 8.4) were associated with failure (P= 0.001 and 0.015, respectively). A PAP MIC of ≥4 mg/liter and ICU admission were significant for treatment failure for patients with MRSA IE. The PAP-AUC ratio of ≥0.9035 predicted failure consistent with the hVISA definition. The role of population MIC analysis in predicting outcome with MRSA infections warrants further investigation.

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Establishment of an AUC0–24 Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02535-16 ◽

2017 ◽

Vol 61 (5) ◽

Cited By ~ 35

Author(s):

R. Chavada ◽

N. Ghosh ◽

I. Sandaradura ◽

M. Maley ◽

S. J. Van Hal

Keyword(s):

Staphylococcus Aureus ◽

Regression Tree ◽

Kidney Injury ◽

Classification And Regression Tree ◽

Time Curve ◽

Methicillin Resistant ◽

Content Type ◽

Cart Analysis ◽

Vancomycin Trough ◽

Trough Concentrations

ABSTRACT Unlike vancomycin trough concentrations, data on the utility of vancomycin pharmacokinetic (PK) parameters, namely, the area under the concentration-time curve from 0 to 24 h (AUC0–24), in predicting acute kidney injury (AKI) are limited. Our aim was to investigate this relationship in patients receiving vancomycin therapy for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B). A single-center retrospective observational cohort study involving 127 consecutive MRSA-B patients was conducted to examine the incidence of AKI (defined as serum creatinine of ≥0.5 mg/liter and a 50% increase from baseline) and vancomycin exposure parameters associated with nephrotoxicity. Bayesian estimation was used to predict individual vancomycin AUC0–24. All patients received vancomycin monotherapy for a minimum of 14 days following the diagnosis of MRSA-B. AKI was observed in 15.7% of patients (20/127). Clinical characteristics were similar between patients with and without AKI. At steady state, higher vancomycin trough concentrations were associated with AKI (17.2 mg/liter versus 13.1 mg/liter; P = 0.003). A vancomycin AUC0–24 threshold for AKI of >563 mg · h/liter was detected by classification and regression tree (CART) analysis; patients with exposures above this threshold were significantly more likely to experience AKI than patients with lower vancomycin exposures (40% [8/20] versus 11.2% [12/107]; P = 0.002). This parameter remained an independent predictor of AKI on multivariate logistic regression (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.57 to 16.29; P = 0.006) and was a better predictor of nephrotoxicity than vancomycin trough concentrations. Overall, AKI is associated with higher vancomycin exposure as measured by AUC0–24. These results suggest that individualized patient dosing may be possible with dose modifications directed toward established pharmacodynamic targets while balancing AKI risks.

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Participation of CD11c+Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung

Infection and Immunity ◽

10.1128/iai.01299-10 ◽

2011 ◽

Vol 79 (5) ◽

pp. 1898-1904 ◽

Cited By ~ 31

Author(s):

Francis J. Martin ◽

Dane Parker ◽

Bryan S. Harfenist ◽

Grace Soong ◽

Alice Prince

Keyword(s):

Staphylococcus Aureus ◽

Pulmonary Infection ◽

Fluorescent Protein ◽

Pulmonary Inflammation ◽

Bacterial Load ◽

Airway Epithelial Cells ◽

High Morbidity ◽

Proinflammatory Response ◽

Methicillin Resistant ◽

Content Type

ABSTRACTStaphylococcus aureuscauses especially severe pulmonary infection, associated with high morbidity and mortality. In addition to the effects of specific virulence factors, it appears that the intensity of the host proinflammatory response, particularly in the initial stages of infection, contributes substantially to pulmonary damage. We tested the hypothesis that the CD11c+leukocytes are important in the host response to pulmonary infection with methicillin-resistantS. aureus(MRSA) USA300. Clodronate-induced depletion of the alveolar macrophage population resulted in increased numbers of dendritic cells (DCs) and CD4+cells in bronchoalveolar lavage (BAL) fluid and was associated with significantly increased mortality by 18 h followingS. aureusinoculation but had no effect on bacterial load or polymorphonuclear leukocyte (PMN) numbers in the lung. These clodronate-treated mice also had increased expression of interleukin-17A/F (IL-17A/F) and CXCL10 but not of gamma interferon (IFN-γ) or tumor necrosis factor (TNF). Depletion of the dendritic cell population in mice expressing a CD11c-enhanced green fluorescent protein (EGFP)-diphtheria toxin receptor (DTR) transgene was associated with an increased bacterial load in the lung but not increased mortality. Both DCs and airway epithelial cells produced CXCL9, -10, and -11 in response toS. aureus. Pretreatment of mice with an anti-CXCR3 antibody prior to inoculation with MRSA substantially reduced CD4+cells and decreased pulmonary inflammation at 18 h postinfection compared to pretreatment with an IgG control. The results of these experiments suggest that CD11c+cells, the induction of CXCR3 ligand expression, and subsequent CD4+cell recruitment have an important role in the pathogenesis of severe MRSA pulmonary infection.

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Efficacy of Topically Delivered Moxifloxacin against Wound Infection by Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01071-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 2325-2334 ◽

Cited By ~ 34

Author(s):

F. Jacobsen ◽

C. Fisahn ◽

M. Sorkin ◽

I. Thiele ◽

T. Hirsch ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Wound Healing ◽

Wound Infection ◽

High Efficiency ◽

High Morbidity ◽

Methicillin Resistant ◽

Bacterial Counts ◽

Content Type ◽

Promote Wound Healing

ABSTRACTWound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistantStaphylococcus aureus(MRSA) orPseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 105CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.

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Vancomycin AUC/MIC Ratio and 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01485-12 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1654-1663 ◽

Cited By ~ 114

Author(s):

Natasha E. Holmes ◽

John D. Turnidge ◽

Wendy J. Munckhof ◽

J. Owen Robinson ◽

Tony M. Korman ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Clinical Success ◽

Test Method ◽

Classification And Regression Tree ◽

Therapeutic Monitoring ◽

Attributable Mortality ◽

Content Type ◽

Significant Difference ◽

Vancomycin Trough ◽

Trough Levels

ABSTRACTA ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥400 has been associated with clinical success when treatingStaphylococcus aureuspneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all seriousS. aureusinfections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a “real-world” context by following a cohort of 182 patients withS. aureusbacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively;P< 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P= 0.132 andP= 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P= 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

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Efficacy of Novel Antistaphylococcal Ectolysin P128 in a Rat Model of Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01358-17 ◽

2017 ◽

Vol 62 (2) ◽

Cited By ~ 8

Author(s):

Shankaramurthy Channabasappa ◽

Murali Durgaiah ◽

Ravisha Chikkamadaiah ◽

Senthil Kumar ◽

Amruta Joshi ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bactericidal Activity ◽

Rat Model ◽

Bacterial Load ◽

High Morbidity ◽

Bolus Administration ◽

Methicillin Resistant ◽

Content Type ◽

Systemic Infections ◽

Novel Therapeutic

ABSTRACTStaphylococcus aureuscauses systemic infections with high morbidity and mortality, and the emergence of drug-resistant strains is a rapidly growing clinical concern. Novel therapeutic agents are required to tackleS. aureusinfections. P128 is a bacteriophage-derived chimeric ectolysin with potent and rapid bactericidal activity againstS. aureus. In the present study, the efficacy of P128 was evaluated in a newly developed rat model ofS. aureusbacteremia. Prior toin vivotesting, P128 was shown to be stable in whole blood by incubation in rat blood for up to 6 h and testing its bactericidal activity against the methicillin-resistantS. aureusisolate USA300. Rats succumbed to intravenous challenge with 109CFU ofS. aureusUSA300, resulting in 80 to 100% mortality by day 14. Evaluation of the bacterial load in various organs at 96 h postinfection revealed high bacterial counts in the kidney, and this correlated with the presence of renal abscesses. Treatment of infected animals with P128 either by intravenous bolus administration via tail vein or by 1-h infusion via the jugular vein at 2 h postinfection resulted in the dose-dependent survival of rats. P128 treatment also resulted in very few or no abscesses in the kidneys. These data show that P128 is stable in the physiological milieu and that intravenous treatment with P128 is highly effective in rescuing rats fromS. aureusbacteremia. P128 can be a novel therapeutic option for treatment ofS. aureussystemic infections.

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Caspofungin Inhibits Mixed Biofilms of Candida albicans and Methicillin-Resistant Staphylococcus aureus and Displays Effectiveness in Coinfected Galleria mellonella Larvae

Microbiology Spectrum ◽

10.1128/spectrum.00744-21 ◽

2021 ◽

Author(s):

Gaby Scheunemann ◽

Bruna N. Fortes ◽

Nilton Lincopan ◽

Kelly Ishida

Keyword(s):

Staphylococcus Aureus ◽

Candida Albicans ◽

Methicillin Resistant Staphylococcus Aureus ◽

Galleria Mellonella ◽

Bloodstream Infections ◽

Mortality Rates ◽

Morbidity And Mortality ◽

High Morbidity ◽

Methicillin Resistant ◽

Content Type

Infections by microorganisms resistant to antimicrobials is a major challenge that leads to high morbidity and mortality rates and increased time and cost with hospitalization. It was estimated that 27 to 56% of bloodstream infections by C. albicans are polymicrobial, with S. aureus being one of the microorganisms commonly coisolated worldwide.

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Daptomycin Improves Outcomes Regardless of Vancomycin MIC in a Propensity-Matched Analysis of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00227-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 5841-5848 ◽

Cited By ~ 25

Author(s):

Kimberly C. Claeys ◽

Evan J. Zasowski ◽

Anthony M. Casapao ◽

Abdalhamid M. Lagnf ◽

Jerod L. Nagel ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Logistic Regression ◽

Bloodstream Infections ◽

Attributable Mortality ◽

Stepwise Logistic Regression ◽

Clinical Failure ◽

Methicillin Resistant ◽

Content Type ◽

Vancomycin Mics ◽

Significant Difference

ABSTRACTVancomycin remains the mainstay treatment for methicillin-resistantStaphylococcus aureus(MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ≥7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%;P= 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%;P= 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC.

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Association between Vancomycin Day 1 Exposure Profile and Outcomes among Patients with Methicillin-Resistant Staphylococcus aureus Infective Endocarditis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03970-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 2978-2985 ◽

Cited By ~ 35

Author(s):

Anthony M. Casapao ◽

Thomas P. Lodise ◽

Susan L. Davis ◽

Kimberly C. Claeys ◽

Ravina Kullar ◽

...

Keyword(s):

Infective Endocarditis ◽

Medical Center ◽

Regression Tree ◽

Classification And Regression Tree ◽

Attributable Mortality ◽

Time Curve ◽

Minimum Concentration ◽

Cart Analysis ◽

Increased Risk ◽

Exposure Profile

ABSTRACTGiven the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0–24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0–24/MIC as determined by BMD of ≤600 relative to those with AUC0–24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively,P= 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37;P= 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0–24/MIC as determined by BMD of ≤600 present an increased risk of failure.

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Relationship between Vancomycin MIC and Failure among Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00113-08 ◽

2008 ◽

Vol 52 (9) ◽

pp. 3315-3320 ◽

Cited By ~ 395

Author(s):

T. P. Lodise ◽

J. Graves ◽

A. Evans ◽

E. Graffunder ◽

M. Helmecke ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bloodstream Infections ◽

Fold Increase ◽

Classification And Regression Tree ◽

Inclusion Criteria ◽

Vancomycin Therapy ◽

Methicillin Resistant ◽

Adjusted Risk ◽

Cart Analysis ◽

Vancomycin Mics

ABSTRACT There is growing concern that vancomycin has diminished activity for methicillin-resistant Staphylococcus aureus (MRSA) infections, with vancomycin MICs at the high end of the CLSI susceptibility range. Despite this growing concern, there are limited clinical data to support this notion. To better elucidate this, a retrospective cohort study was conducted among patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and May 2007. The inclusion criteria were as follows: at least 18 years old, nonneutropenic, with an MRSA culture that met the CDC criteria for bloodstream infection, had received vancomycin therapy within 48 h of the index blood culture, and survived >24 h after vancomycin administration. Failure was defined as 30-day mortality, bacteremia ≥10 days on vancomycin therapy, or a recurrence of MRSA bacteremia within 60 days of vancomycin discontinuation. Classification and regression tree (CART) analysis identified the vancomycin MIC breakpoint associated with an increased probability of failure. During the study period, 92 patients met the inclusion criteria. The vancomycin MIC breakpoint derived by CART analysis was ≥1.5 mg/liter. The 66 patients with vancomycin MICs of ≥1.5 mg/liter had a 2.4-fold increase in failure compared to patients with MICs of ≤1.0 mg/liter (36.4% and 15.4%, respectively; P = 0.049). In the Poisson regression, a vancomycin MIC of ≥1.5 mg/liter was independently associated with failure (adjusted risk ratio, 2.6; 95% confidence interval, 1.3 to 5.4; P = 0.01). These data strongly suggest that patients with MRSA bloodstream infections with vancomycin MICs of ≥1.5 mg/liter respond poorly to vancomycin. Alternative anti-MRSA therapies should be considered for these patients.

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1596. Impact of Vancomycin Area Under Curve on Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections (BSI)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1460 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S582-S582

Author(s):

Sara Alosaimy ◽

Sarah C J Jorgensen ◽

Abdulhamid Lagnf ◽

Evan J Zasowski ◽

Trang D Trinh ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Medical Center ◽

Univariate Analysis ◽

Bloodstream Infections ◽

Classification And Regression Tree ◽

Apache Ii Score ◽

Multivariable Logistic Regression Analysis ◽

Methicillin Resistant ◽

Cart Analysis

Abstract Background Persistent Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with significant morbidity, mortality, and healthcare expenditures. Vancomycin (VAN) remains the treatment of choice for invasive MRSA BSI. Current guidelines for the treatment of MRSA BSI recommend a VAN AUC24h/MIC ratio ≥400. The Detroit Medical Center (DMC) implemented an AUC guided dosing strategy. However, data on the association between AUC24h and clinical outcomes in MRSA BSI are limited. We aimed to evaluate the association between VAN AUC24h and persistent bacteremia (PB) among patients with BSI. Methods Multi-center, retrospective cohort study from January 2015 to November 2018. We included adult patients with MRSA bacteremia treated with VAN for which AUC24h monitoring was performed. AUC was measured using 2-level guided dosing. The primary outcome was PB defined as continued positive cultures >72 hours after VAN initiation. Classification and Regression Tree (CART) analysis was performed to determine the AUC24h breakpoint (BP) most predictive of PB in the cohort. Mann–Whitney and Fischer exact tests were used for univariate analysis. The independent association between AUC24h, dichotomized at the CART-derived cut-point, was then examined through multivariable logistic regression analysis. Results Overall, 137 patients were included. The median age was 59 (18–85) years, 69.3% male, and 75.2% African American predominance. Most common sources of BSI were skin/soft tissue (39.4%), pneumonia (25.5%), and osteoarticular (16.8%). The median APACHE II score was 13 (8–20). Median time to microbiological clearance was 2.5 days (0.5–12). Patients with AUC24h ≤ 406.25 were more likely to have PB compared with those with AUC24h > 406.25 (59.4% and 35.2%, respectively; P = 0.002). After controlling for age, intensive care stay, and concomitant β-lactam therapy; AUC of ≤ 406.25 (aOR 2.767, 95% CI 1.212–6.318) and endocarditis (aOR 2.87, 95% CI 1.079–7.638) were independently associated with PB. Conclusion VAN AUC24h BP of <406.25 was independently associated with PB in patients with MRSA BSI. Our findings underscore the importance of VAN dose optimization to achieve timely bacterial clearance in MRSA bacteremia. Disclosures All authors: No reported disclosures.

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