Pharmacodynamics of daptomycin in combination with other antibiotics for the treatment of enterococcal bacteraemia.
Int J Antimicrob Agents
; 54(3): 346-350, 2019 Sep.
Article
in En
| MEDLINE
| ID: mdl-31284042
ABSTRACT
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 ß-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 ß-lactam (94.6%). Examining the threshold in low-acuity patients (nâ¯=â¯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%; Pâ¯=â¯0.015). The difference remained significant in a multivariable logistic regression model that controlled for infection source and immunosuppression (Pâ¯=â¯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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Gram-Positive Bacterial Infections
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Enterococcus
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Bacteremia
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Daptomycin
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Anti-Bacterial Agents
Type of study:
Prognostic_studies
/
Systematic_reviews
Limits:
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Int J Antimicrob Agents
Year:
2019
Type:
Article
Affiliation country:
United States