scholarly journals Multicenter Cohort Study of Ceftaroline versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

2021 ◽  
Author(s):  
Evan J Zasowski ◽  
Trang D Trinh ◽  
Kimberly C Claeys ◽  
Abdalhamid M Lagnf ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cohort Study ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Study Drug ◽  
Bloodstream Infections ◽  
Risk Difference ◽  
Multicenter Cohort Study ◽  
Methicillin Resistant ◽  
Composite Failure

Abstract Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥ 72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥ 7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% non-inferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was non-inferior to daptomycin with respect to composite failure [39% daptomycin, 32.5% ceftaroline; weighted risk difference (95% CI) 7.0% (-5.0 – 19.0%)]. No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = 0.034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = 0.001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

scholarly journals The Emperor’s New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE)

2019 ◽  
Vol 70 (8) ◽  
pp. 1536-1545 ◽  
Author(s):  
Thomas P Lodise ◽  
Susan L Rosenkranz ◽  
Matthew Finnemeyer ◽  
Scott Evans ◽  
Matthew Sims ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Hospitalized Patients ◽  
Methicillin Resistant ◽  
Primary Endpoints ◽  
Persistent Bacteremia

Abstract Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

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 >14.8% (base case: 14.0%) or >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 < 16.4% (base case: 27.2%). In two-way sensitivity analyses, daptomycin was favored if linezolid microbiological failure and ADE-related discontinuation rates were >19% and > 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)

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