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Continuous beta-lactam infusion in critically ill patients: the clinical evidence.

Abdul-Aziz MH, Dulhunty JM, Bellomo R, Lipman J, Roberts JA - Ann Intensive Care (2012)

Bottom Line: No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet.This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic (PK/PD) data.A lack of significance in clinical outcome studies may be due to several methodological flaws potentially masking the benefits of continuous infusion observed in preclinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia. Joel_Dulhunty@health.qld.gov.au.

ABSTRACT
There is controversy over whether traditional intermittent bolus dosing or continuous infusion of beta-lactam antibiotics is preferable in critically ill patients. No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet. This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic (PK/PD) data. A lack of significance in clinical outcome studies may be due to several methodological flaws potentially masking the benefits of continuous infusion observed in preclinical studies. In this review, we explore the methodological shortcomings of the published clinical studies and describe the criteria that should be considered for performing a definitive clinical trial. We found that most trials utilized inconsistent antibiotic doses and recruited only small numbers of heterogeneous patient groups. The results of these trials suggest that continuous infusion of beta-lactam antibiotics may have variable efficacy in different patient groups. Patients who may benefit from continuous infusion are critically ill patients with a high level of illness severity. Thus, future trials should test the potential clinical advantages of continuous infusion in this patient population. To further ascertain whether benefits of continuous infusion in critically ill patients do exist, a large-scale, prospective, multinational trial with a robust design is required.

No MeSH data available.


Related in: MedlinePlus

Pharmacokinetic and pharmacodynamic parameters of antibiotics on a concentration vs. time curve. T>MIC, time that a drug’s plasma concentration remains above the minimum inhibitory concentration (MIC) for a dosing period; Cmax, maximum plasma antibiotic concentration; AUC0-24, area under the concentration-time curve during a 24-hour time period.
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Figure 1: Pharmacokinetic and pharmacodynamic parameters of antibiotics on a concentration vs. time curve. T>MIC, time that a drug’s plasma concentration remains above the minimum inhibitory concentration (MIC) for a dosing period; Cmax, maximum plasma antibiotic concentration; AUC0-24, area under the concentration-time curve during a 24-hour time period.

Mentions: Antibiotic pharmacodynamics (PD) is the discipline that attempts to relate PK parameters to the ability of an antibiotic to kill or inhibit the growth of bacterial pathogens [9]. Antibiotics can be classified based on these PD characteristics. Generally, antibiotics are classified into three categories based on their mode of bacterial killing: (1) concentration-dependent; 2) time-dependent; or 3) both (Figure 1). The first category includes antibiotics, such as aminoglycosides, where the best predictor of efficacy is the ratio of peak drug concentration (Cmax) to minimum inhibitory concentration (MIC; Cmax/MIC) [10,11]. Some antibiotics, such as fluoroquinolones and glycopeptides, are more complex and exhibit both a concentration and time-dependent kill characteristics where the best predictor of efficacy is the ratio of area under the concentration time curve during a 24-hour period (AUC0-24) to MIC (AUC0-24/MIC). Therefore, increasing the dose or/and concentration for these antibiotics can be logically expected to enhance the rate and extent of bacterial killing [12,13]. In contrast, higher beta-lactam concentrations do not significantly influence their efficacy. Based on numerous in vitro and in vivo experimental data, it is the duration of effective antibiotic exposure that is more important for these time-dependent antibiotics [14-17].


Continuous beta-lactam infusion in critically ill patients: the clinical evidence.

Abdul-Aziz MH, Dulhunty JM, Bellomo R, Lipman J, Roberts JA - Ann Intensive Care (2012)

Pharmacokinetic and pharmacodynamic parameters of antibiotics on a concentration vs. time curve. T>MIC, time that a drug’s plasma concentration remains above the minimum inhibitory concentration (MIC) for a dosing period; Cmax, maximum plasma antibiotic concentration; AUC0-24, area under the concentration-time curve during a 24-hour time period.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475088&req=5

Figure 1: Pharmacokinetic and pharmacodynamic parameters of antibiotics on a concentration vs. time curve. T>MIC, time that a drug’s plasma concentration remains above the minimum inhibitory concentration (MIC) for a dosing period; Cmax, maximum plasma antibiotic concentration; AUC0-24, area under the concentration-time curve during a 24-hour time period.
Mentions: Antibiotic pharmacodynamics (PD) is the discipline that attempts to relate PK parameters to the ability of an antibiotic to kill or inhibit the growth of bacterial pathogens [9]. Antibiotics can be classified based on these PD characteristics. Generally, antibiotics are classified into three categories based on their mode of bacterial killing: (1) concentration-dependent; 2) time-dependent; or 3) both (Figure 1). The first category includes antibiotics, such as aminoglycosides, where the best predictor of efficacy is the ratio of peak drug concentration (Cmax) to minimum inhibitory concentration (MIC; Cmax/MIC) [10,11]. Some antibiotics, such as fluoroquinolones and glycopeptides, are more complex and exhibit both a concentration and time-dependent kill characteristics where the best predictor of efficacy is the ratio of area under the concentration time curve during a 24-hour period (AUC0-24) to MIC (AUC0-24/MIC). Therefore, increasing the dose or/and concentration for these antibiotics can be logically expected to enhance the rate and extent of bacterial killing [12,13]. In contrast, higher beta-lactam concentrations do not significantly influence their efficacy. Based on numerous in vitro and in vivo experimental data, it is the duration of effective antibiotic exposure that is more important for these time-dependent antibiotics [14-17].

Bottom Line: No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet.This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic (PK/PD) data.A lack of significance in clinical outcome studies may be due to several methodological flaws potentially masking the benefits of continuous infusion observed in preclinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia. Joel_Dulhunty@health.qld.gov.au.

ABSTRACT
There is controversy over whether traditional intermittent bolus dosing or continuous infusion of beta-lactam antibiotics is preferable in critically ill patients. No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet. This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic (PK/PD) data. A lack of significance in clinical outcome studies may be due to several methodological flaws potentially masking the benefits of continuous infusion observed in preclinical studies. In this review, we explore the methodological shortcomings of the published clinical studies and describe the criteria that should be considered for performing a definitive clinical trial. We found that most trials utilized inconsistent antibiotic doses and recruited only small numbers of heterogeneous patient groups. The results of these trials suggest that continuous infusion of beta-lactam antibiotics may have variable efficacy in different patient groups. Patients who may benefit from continuous infusion are critically ill patients with a high level of illness severity. Thus, future trials should test the potential clinical advantages of continuous infusion in this patient population. To further ascertain whether benefits of continuous infusion in critically ill patients do exist, a large-scale, prospective, multinational trial with a robust design is required.

No MeSH data available.


Related in: MedlinePlus