scholarly journals Vancomycin AUC24/MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization

2011 ◽  
Vol 56 (2) ◽  
pp. 634-638 ◽  
Author(s):  
Jack Brown ◽  
Kristen Brown ◽  
Alan Forrest
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Apache Ii ◽  
Bayesian Estimator ◽  
Attributable Mortality ◽  
Apache Ii Score ◽  
Main Diagnosis ◽  
Methicillin Resistant

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE). The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC24)/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC24/MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC24/MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC24was determined using a maximuma posterioriprobability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC24/MIC ratio and AM was <211. Patients with an AUC24/MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC24/MIC ratio of ≥211 (38 and 8%, respectively;P= 0.02). In bivariate analysis the APACHE-II score and an AUC24/MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24;P= 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4;P= 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC24/MIC ratio of <211. We believe further investigations are warranted.

scholarly journals Prediction of Failure in Vancomycin-Treated Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: a Clinically Useful Risk Stratification Tool

2011 ◽  
Vol 55 (10) ◽  
pp. 4581-4588 ◽  
Author(s):  
Carol L. Moore ◽  
Mei Lu ◽  
Faiqa Cheema ◽  
Paola Osaki-Kiyan ◽  
Mary Beth Perri ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Risk Stratification ◽  
Bloodstream Infection ◽  
Apache Ii ◽  
Risk Level ◽  
Apache Ii Score ◽  
City Hospital ◽  
Clinical Failure ◽  
Methicillin Resistant ◽  
Risk Stratification Tool

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) is a common cause of bloodstream infection (BSI) and is often associated with invasive infections and high rates of mortality. Vancomycin has remained the mainstay of therapy for serious Gram-positive infections, particularly MRSA BSI; however, therapeutic failures with vancomycin have been increasingly reported. We conducted a comprehensive evaluation of the factors (patient, strain, infection, and treatment) involved in the etiology and management of MRSA BSI to create a risk stratification tool for clinicians. This study included consecutive patients with MRSA BSI treated with vancomycin over 2 years in an inner-city hospital in Detroit, MI. Classification and regression tree analysis (CART) was used to develop a risk prediction model that characterized vancomycin-treated patients at high risk of clinical failure. Of all factors, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, with a cutoff point of 14, was found to be the strongest predictor of failure and was used to split the population into two groups. Forty-seven percent of the population had an APACHE-II score < 14, a value that was associated with low rates of clinical failure (11%) and mortality (4%). Fifty-four percent of the population had an APACHE-II score ≥ 14, which was associated with high rates of clinical failure (35%) and mortality (23%). The risk stratification model identified the interplay of three other predictors of failure, including the vancomycin MIC as determined by Vitek 2 analysis, the risk level of the source of BSI, and the USA300 strain type. This model can be a useful tool for clinicians to predict the likelihood of success or failure in vancomycin-treated patients with MRSA bloodstream infection.

scholarly journals 2250. Combination Vancomycin Plus Cefazolin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S769-S769
Author(s):  
Sarah C J Jorgensen ◽  
Trang D Trinh ◽  
Evan J Zasowski ◽  
Sara Alosaimy ◽  
Sarah Melvin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Initiation ◽  
Bloodstream Infections ◽  
Apache Ii ◽  
Independent Effect ◽  
Apache Ii Score ◽  
Clinical Failure ◽  
Methicillin Resistant

Abstract Background Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone. Methods Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation. Results A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table: Conclusion Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI. Disclosures All authors: No reported disclosures.

scholarly journals 1073. Predictors of Vancomycin Switch or Escalation in Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S321-S321
Author(s):  
Abdalhamid M Lagnf ◽  
Sarah Jorgensen ◽  
Evan J Zasowski ◽  
Trang D Trinh ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Logistic Regression ◽  
Infective Endocarditis ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Apache Ii ◽  
Research Support ◽  
Methicillin Resistant ◽  
Multivariable Logistic Regression ◽  
The Impact ◽  
Research Grant

Abstract Background Vancomycin (VAN) is the primary agent for the treatment methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI). VAN is frequently combined with or switched to a second anti-MRSA agent for the treatment of serious BSI because VAN monotherapy has been linked to treatment failures. We aimed to determine the potential risk factors for patients with MRSA BSI who switched or had therapy escalated. Methods This was a multicenter, retrospective cohort study of adults (≥18 years) initially treated with VAN (&gt;24 hours) for MRSA BSI between 2006 and 2018. Patients with a respiratory source were excluded. Baseline clinical and infection characteristics were compared between patients who received VAN as the sole anti-MRSA agent and continued on VAN until discharge and patients who switched or had a second anti-MRSA agent added during their admission (switch/escalate group). Multivariable logistic regression was performed to identify independent predictors of therapy switch or escalation. Results A total of 195 patients were included (66 VAN and 129 switch/escalate). The mean (SD) age of the study population was 56 (15.5) years, 68.2% were male, and 81.0% were African-American. Most (80%) of patient had community-onset BSI. The median (IQR) Charlson Comorbidity index and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 3 (1–5) and 14 (8–20), respectively. The major sources of BSI were skin/soft tissue (24.6%), infective endocarditis (24.1%), and bone/joint (23.1%). Median (IQR) time to switch/escalation was 67 (44–97) hours. In multivariable logistic regression analysis, infective endocarditis (aOR 6.2, 95% CI 2.2–16), hospitalization in the past 90 days (aOR 2.0, 95% CI 1.0–4.0), and APACHE II (aOR 1.07, 95% CI 1.01–1.12) were independently associated with switch/escalation. Conclusion We have identified a number of baseline clinical and infection characteristics that should be taken into account for clinicians to predict the likelihood of switch or escalation in vancomycin treated patients with MRSA BSI. Further studies evaluating the impact of up front alternative therapies in these higher risk patients are needed. Disclosures S. L. Davis, Achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. Nabriva: Scientific Advisor, Consulting fee. Zavante: Scientific Advisor, Consulting fee. M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

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

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.

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

2014 ◽  
Vol 58 (8) ◽  
pp. 4636-4641 ◽  
Author(s):  
Anthony M. Casapao ◽  
Susan L. Davis ◽  
John Paul McRoberts ◽  
Abdalhamid M. Lagnf ◽  
Sonal Patel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Treatment Failure ◽  
Classification And Regression Tree ◽  
Attributable Mortality ◽  
High Morbidity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Icu Admission ◽  
Cart Analysis

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.

scholarly journals Clinical Risk Factors for Infective Endocarditis in Staphylococcus aureus Bacteremia

2017 ◽  
Vol 44 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Vincent Bryan D. Salvador ◽  
Bikash Chapagain ◽  
Astha Joshi ◽  
Debra J. Brennessel
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
High Risk ◽  
Transesophageal Echocardiography ◽  
Univariate Analysis ◽  
Clinical Risk Factors ◽  
Methicillin Resistant ◽  
Clinical Risk ◽  
Staphylococcus Aureus Bacteremia

Crucial to the management of staphylococcal bacteremia is an accurate evaluation of associated endocarditis, which has both therapeutic and prognostic implications. Because the clinical presentation of endocarditis can be nonspecific, the judicious use of echocardiography is important in distinguishing patients at high risk of developing endocarditis. In the presence of high-risk clinical features, an early transesophageal echocardiogram is warranted without prior transthoracic echocardiography. The purpose of this study was to investigate the clinical risk factors for staphylococcal infective endocarditis that might warrant earlier transesophageal echocardiography and to describe the incidence of endocarditis in cases of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia. A retrospective case-control study was conducted by means of chart review of 91 patients consecutively admitted to a community hospital from January 2009 through January 2013. Clinical risk factors of patients with staphylococcal bacteremia were compared with risk factors of patients who had definite diagnoses of infective endocarditis. There were 69 patients with bacteremia alone (76%) and 22 patients with endocarditis (24%), as verified by echocardiography. Univariate analysis showed that diabetes mellitus (P=0.024), the presence of an automatic implantable cardioverter-defibrillator/pacemaker (P=0.006) or a prosthetic heart valve (P=0.003), and recent hospitalization (P=0.048) were significantly associated with developing infective endocarditis in patients with S. aureus bacteremia. The incidence of methicillin-resistant and methicillin-sensitive S. aureus bacteremia was similar in the bacteremia and infective-endocarditis groups (P=0.437). In conclusion, identified high-risk clinical factors in the presence of bacteremia can suggest infective endocarditis. Early evaluation with transesophageal echocardiography might well be warranted.

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