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Pharmacodynamics of daptomycin in combination with other antibiotics for the treatment of enterococcal bacteraemia.
Journal article

Pharmacodynamics of daptomycin in combination with other antibiotics for the treatment of enterococcal bacteraemia.

  • Avery LM Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
  • Kuti JL Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
  • Weisser M Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
  • Egli A Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland; Applied Microbiology Research, University of Basel, Basel, Switzerland.
  • Rybak MJ Anti-Infective Research Laboratory, College of Pharmacy, School of Medicine, Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA.
  • Zasowski EJ Anti-Infective Research Laboratory, College of Pharmacy, School of Medicine, Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
  • Arias CA Center for Antimicrobial Resistance and Microbial Genomics and Division of Infectious Diseases, University of Texas Health Science Center, McGovern Medical School at Houston, Houston, Texas, USA; Center for Infectious Diseases, University of Texas Health Science Center, School of Public Health, Houston, Texas, USA; Molecular Genetics and Antimicrobial Resistance Unit-International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia.
  • Contreras GA Center for Antimicrobial Resistance and Microbial Genomics and Division of Infectious Diseases, University of Texas Health Science Center, McGovern Medical School at Houston, Houston, Texas, USA.
  • Chong PP Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • Aitken SL Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • DiPippo AJ Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Wang JT Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Britt NS Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA; Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, Kansas, USA.
  • Nicolau DP Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA; Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA. Electronic address: david.nicolau@hhchealth.org.
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  • 2019-07-09
Published in:
  • International journal of antimicrobial agents. - 2019
Bacteraemia
Combination therapy
Daptomycin
Enterococcus
Pharmacodynamics
Aged
Anti-Bacterial Agents
Bacteremia
Daptomycin
Drug Interactions
Drug Therapy, Combination
Enterococcus
Female
Gram-Positive Bacterial Infections
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Survival Analysis
Treatment Outcome
English Daptomycin is commonly prescribed in combination with other antibiotics for treatment of enterococcal bacteraemia. Whilst a free drug area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) ratio >27.4 is associated with 30-day survival with daptomycin monotherapy, it is unknown whether receipt of other antibiotics affects this threshold. Data were pooled from seven published trials assessing outcomes in daptomycin-treated enterococcal bacteraemia, including patients receiving daptomycin (≥72 h) and any β-lactam, intravenous aminoglycoside, linezolid, tigecycline and/or vancomycin. Exposures were calculated using a published population pharmacokinetic model based on creatinine clearance, 90% protein binding and daptomycin Etest MIC. The fAUC/MIC threshold predictive of 30-day survival was determined by classification and regression tree analysis. Following pooling of data, 240 adults were included; 137 (57.1%) were alive at 30 days. A majority of patients were immunosuppressed (65.8%) and received a β-lactam (94.6%). Examining the threshold in low-acuity patients (n = 135) to control for co-morbidities, these patients were more likely to survive when fAUC/MIC >12.3 was achieved (63.2% vs. 20.0%; P = 0.015). The difference remained significant in a multivariable logistic regression model that controlled for infection source and immunosuppression (P = 0.017). This threshold is 2-fold lower than that observed with daptomycin monotherapy. Probabilities of threshold attainment using a 10 mg/kg/day dose were 100% for isolates with MICs ≤ 2 mg/L and 95.2% for a 12 mg/kg/day dose for MICs of 4 mg/L. These data support the use of high-dose daptomycin in combination with another antibiotic for treatment of enterococcal bacteraemia.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/232485
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