Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
Pharmacodynamic Analysis of Daptomycin-treated Enterococcal Bacteremia: It Is Time to Change the Breakpoint.
Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The Global Prevalence of Daptomycin, Tigecycline, and Linezolid-ResistantFrontiers in medicine · 2021Pooled it
- Outcomes and Adverse Events Among Patients with Vancomycin-Resistant Enterococcal Bloodstream Infection Treated with Daptomycin Doses Greater than 12 mg/kg.Infectious diseases and therapy · 2026Article
- Comprehensive pharmacokinetic/pharmacodynamic analysis of commercially available premixed daptomycin preparations againstJAC-antimicrobial resistance · 2026Article
- Outcomes of early oral antibiotic transition for the treatment of uncomplicated enterococcal bacteremia.Antimicrobial stewardship & healthcare epidemiology : ASHE · 2026Article
- Temporal Shifts in Etiological Agents and Trends in Antimicrobial Resistance of Bloodstream Infection in Southwest China from 2016 to 2023.Infection and drug resistance · 2025Article
- Global impact of antibacterial resistance in patients with hematologic malignancies and hematopoietic cell transplant recipients.Transplant infectious disease : an official journal of the Transplantation Society · 2023Review
- Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.Clinical microbiology reviews · 2023Review
- Treatment decisions in VRE bacteraemia: a survey of infectious diseases pharmacists.JAC-antimicrobial resistance · 2023Article
- The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study.Infectious diseases and therapy · 2023Article
- Successful Treatment of Vancomycin-ResistantInfection & chemotherapy · 2022Article
- A High Daptomycin Dose Is Associated with Better Bacterial Clearance in Infections Caused by Vancomycin-Resistant Enterococcus faecium Regardless of Daptomycin Minimum Inhibitory Concentration in a Rat Infective Endocarditis Model.Microbiology spectrum · 2022Article
- Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues.Clinical pharmacokinetics · 2022Article
- Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update.Antibiotics (Basel, Switzerland) · 2022Article
- Implementation and Comparison of Two Pharmacometric Tools for Model-Based Therapeutic Drug Monitoring and Precision Dosing of Daptomycin.Pharmaceutics · 2022Article
- High-Dose Daptomycin and Clinical Applications.The Annals of pharmacotherapy · 2021Review
- Daptomycin versus Glycopeptides for the Treatment ofAntibiotics (Basel, Switzerland) · 2021Article
- Clinical Pharmacokinetics of Daptomycin.Clinical pharmacokinetics · 2021Review
- Impact of Daptomycin Dose Exposure Alone or in Combination with β-Lactams or Rifampin against Vancomycin-Resistant Enterococci in anAntimicrobial agents and chemotherapy · 2020Article
- Assessment of TedizolidAntimicrobial agents and chemotherapy · 2020Article
- One Size Fits All? Application of Susceptible-Dose-Dependent Breakpoints to Pediatric Patients and Laboratory Reporting.Journal of clinical microbiology · 2019Review
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Authors and funding
14 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundCurrently, there is debate over whether the daptomycin susceptibility breakpoint for enterococci (ie, minimum inhibitory concentration [MIC] ≤4 mg/L) is appropriate. In bacteremia, observational data support prescription of high doses (>8 mg/kg). However, pharmacodynamic targets associated with positive patient outcomes are undefined.
methodsData were pooled from observational studies that assessed outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antienterococcal antibiotic and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of survival at 30 days was identified by classification and regression tree analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs.
resultsOf 114 patients who received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. A fAUC/MIC >27.43 was associated with survival in low-acuity (n = 77) patients (68.9 vs 37.5%, P = .006), which remained significant after adjusting for infection source and immunosuppression (P = .026). The PTA for a 6-mg/kg/day (every 24 hours) dose was 1.5%-5.5% when the MIC was 4 mg/L (ie, daptomycin-susceptible) and 91.0%-97.9% when the MIC was 1 mg/L.
conclusionsFor enterococcal bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of reevaluation of the susceptibility breakpoint.
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