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 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 Standardized Treatment and Assessment Pathway Improves Mortality in Adults with Methicillin-resistant Staphylococcus aureus Bacteremia: STAPH-Study

2021 ◽  
Author(s):  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Taylor Morrisette ◽  
Sarah C J Jorgensen ◽  
Trang D Trinh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infectious Diseases ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Medical Center ◽  
Bloodstream Infections ◽  
Clinical Implementation ◽  
Methicillin Resistant ◽  
Confounding Variables ◽  
Early Use

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN)/daptomycin (DAP) were combined with beta-lactams (BL), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality. Methods The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard-of-care (VAN or DAP) and a mandatory infectious diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013-2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables. Results Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared to pre-pathway (PRE) patients (n=379), those treated post-pathway (POST) (n=434) had a significant reduction in 30-day and 90-day mortality; 9.7% in POST vs. 15.6% in PRE (p=0.011) and 12.2% in POST vs. 19.0% in PRE (p=0.007), respectively. The incidence of acute kidney injury (AKI) was higher in the PRE compared to POST; 9.6% vs. 7.2% (p=0.282), respectively. After adjusting for confounding variables including infectious diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% confidence interval [CI], 0.375-0.986). Conclusions Implementation of a MRSA BSI treatment pathway with early use of BL reduced mortality with no increased in AKI. Further prospective evaluation of this pathway approach is warranted.

scholarly journals Blurred Molecular Epidemiological Lines Between the Two Dominant Methicillin-Resistant Staphylococcus aureus Clones

2019 ◽  
Vol 6 (9) ◽  
Author(s):  
Amy C Dupper ◽  
Mitchell J Sullivan ◽  
Kieran I Chacko ◽  
Aaron Mishkin ◽  
Brianne Ciferri ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Medical Center ◽  
Age Groups ◽  
Bloodstream Infections ◽  
Methicillin Resistant ◽  
Peripheral Intravenous Catheter ◽  
Life Threatening ◽  
Catheter Infections

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of health care–associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones. Methods Comprehensive clinical data from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones were compared using logistic regression. Results Molecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (n = 117) and CC8 (n = 110). MRSA BSIs were associated with a 90-day mortality rate of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; P &lt; .001) and in those of nonwhite race (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.51–7.87; P = .003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR, 5.96; 95% CI, 1.51–23.50; P = .01). Conclusions The clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen are crucial to inform management and prevent disease.

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

2008 ◽  
Vol 52 (9) ◽  
pp. 3315-3320 ◽  
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.

scholarly journals Antibiotic Resistance, spa Typing and Clonal Analysis of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Blood of Patients Hospitalized in the Czech Republic

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 395
Author(s):  
Katarina Pomorska ◽  
Vladislav Jakubu ◽  
Lucia Malisova ◽  
Marta Fridrichova ◽  
Martin Musilek ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Czech Republic ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Spa Typing ◽  
The Czech Republic ◽  
Methicillin Resistant ◽  
Mrsa Strains ◽  
Spa Types ◽  
Repeat Pattern

Staphylococcus aureus is one of the major causes of bloodstream infections. The aim of our study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood of patients hospitalized in the Czech Republic between 2016 and 2018. All MRSA strains were tested for antibiotic susceptibility, analyzed by spa typing and clustered using a Based Upon Repeat Pattern (BURP) algorithm. The representative isolates of the four most common spa types and representative isolates of all spa clonal complexes were further typed by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The majority of MRSA strains were resistant to ciprofloxacin (94%), erythromycin (95.5%) and clindamycin (95.6%). Among the 618 strains analyzed, 52 different spa types were detected. BURP analysis divided them into six different clusters. The most common spa types were t003, t586, t014 and t002, all belonging to the CC5 (clonal complex). CC5 was the most abundant MLST CC of our study, comprising of 91.7% (n = 565) of spa-typeable isolates. Other CCs present in our study were CC398, CC22, CC8, CC45 and CC97. To our knowledge, this is the biggest nationwide study aimed at typing MRSA blood isolates from the Czech Republic.

scholarly journals 286. Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Are Daptomycin and Linezolid Favored over Vancomycin and Other Antibiotics?

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S143-S144
Author(s):  
Michelle Vu ◽  
Kenneth Smith ◽  
Sherrie L Aspinall ◽  
Cornelius J Clancy ◽  
Deanna Buehrle
Keyword(s):  
Staphylococcus Aureus ◽  
Cost Effectiveness ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Sensitivity Analyses ◽  
Drug Event ◽  
Base Case ◽  
Health Administration ◽  
Research Support ◽  
Methicillin Resistant

Abstract Background Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. We compared cost-effectiveness of vancomycin and other antibiotic regimens as MRSAB treatment. Methods We estimated cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin, dalbavancin) for Veterans Health Administration (VA) patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure and adverse drug event (ADE)-related discontinuation at 7-days. Results In base-case analyses, linezolid and daptomycin were less expensive and had fewer treatment failures than other regimens at 4 and 6-weeks. Compared to linezolid, daptomycin incremental cost-effectiveness ratios were ~$45,000 (4-weeks) and ~$61,000 (6-weeks) per composite failure avoided, respectively. In one-way sensitivity analyses, daptomycin (4-weeks) was favored over linezolid if linezolid microbiological failure or ADE-related discontinuation rates were &gt;14.8% (base case: 14.0%) or &gt;14.3% (base case: 14.0%), respectively, assuming a willingness to pay (WTP) threshold of $40,000/ composite treatment failure avoided. Vancomycin was favored if its microbiological failure risk was &lt; 16.4% (base case: 27.2%). In two-way sensitivity analyses, daptomycin was favored if linezolid microbiological failure and ADE-related discontinuation rates were &gt;19% and &gt; 16%, respectively. Linezolid, daptomycin and vancomycin were favored in 47%, 39%, and 11% of 4-week probabilistic iterations, respectively, at $40,000 WTP. Conclusion Daptomycin or linezolid are likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed to support safety of linezolid in MRSAB patients. Disclosures Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)

scholarly journals Blurred molecular epidemiological lines between the two dominant methicillin-resistant Staphylococcus aureus clones

2018 ◽  
Author(s):  
Amy C. Dupper ◽  
Mitchell J. Sullivan ◽  
Kieran I. Chacko ◽  
Aaron Mishkin ◽  
Brianne Ciferri ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Medical Center ◽  
Data Extraction ◽  
Age Groups ◽  
Bloodstream Infections ◽  
Methicillin Resistant ◽  
Peripheral Intravenous Catheter ◽  
Life Threatening ◽  
Healthcare Associated

AbstractBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of healthcare-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones.MethodsComprehensive clinical data extraction from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones was compared using logistic regression.ResultsMolecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (N=117) and CC8 (N=110). MRSA BSIs were associated with a 90-day mortality of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; p<0.001) and in non-White race (OR=3.45 95% CI [1.51-7.87]; p=0.003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR=5.96; 95% CI [1.51-23.50]; p=0.01).ConclusionThe clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen is crucial to inform management to prevent disease.

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