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A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients

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Abstract
De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum beta-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum beta-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics.
Keywords
INTENSIVE-CARE UNITS, BETA-LACTAM ANTIBIOTICS, SEVERE SEPSIS, DOSING SIMULATIONS, POPULATION PHARMACOKINETICS, ANTIMICROBIAL THERAPY, SEPTIC SHOCK, CEFEPIME NEUROTOXICITY, ICU, STEWARDSHIP

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MLA
Carlier, Mieke, et al. “A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in de-Escalated Antibiotic Therapy in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 59, no. 8, 2015, pp. 4689–94, doi:10.1128/AAC.00409-15.
APA
Carlier, M., Roberts, J. A., Stove, V., Verstraete, A., Lipman, J., & De Waele, J. (2015). A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 59(8), 4689–4694. https://doi.org/10.1128/AAC.00409-15
Chicago author-date
Carlier, Mieke, Jason A Roberts, Veronique Stove, Alain Verstraete, Jeffrey Lipman, and Jan De Waele. 2015. “A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in de-Escalated Antibiotic Therapy in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 59 (8): 4689–94. https://doi.org/10.1128/AAC.00409-15.
Chicago author-date (all authors)
Carlier, Mieke, Jason A Roberts, Veronique Stove, Alain Verstraete, Jeffrey Lipman, and Jan De Waele. 2015. “A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in de-Escalated Antibiotic Therapy in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 59 (8): 4689–4694. doi:10.1128/AAC.00409-15.
Vancouver
1.
Carlier M, Roberts JA, Stove V, Verstraete A, Lipman J, De Waele J. A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2015;59(8):4689–94.
IEEE
[1]
M. Carlier, J. A. Roberts, V. Stove, A. Verstraete, J. Lipman, and J. De Waele, “A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients,” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 59, no. 8, pp. 4689–4694, 2015.
@article{6715895,
  abstract     = {{De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum beta-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum beta-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics.}},
  author       = {{Carlier, Mieke and Roberts, Jason A and Stove, Veronique and Verstraete, Alain and Lipman, Jeffrey and De Waele, Jan}},
  issn         = {{0066-4804}},
  journal      = {{ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}},
  keywords     = {{INTENSIVE-CARE UNITS,BETA-LACTAM ANTIBIOTICS,SEVERE SEPSIS,DOSING SIMULATIONS,POPULATION PHARMACOKINETICS,ANTIMICROBIAL THERAPY,SEPTIC SHOCK,CEFEPIME NEUROTOXICITY,ICU,STEWARDSHIP}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{4689--4694}},
  title        = {{A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients}},
  url          = {{http://doi.org/10.1128/AAC.00409-15}},
  volume       = {{59}},
  year         = {{2015}},
}

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