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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

Observed steady-state plasma and tissue concentrations for meropenem administered to critically ill patients with sepsis by intermittent bolus dosing and continuous infusion (adapted from Roberts et al. 2009, J Antimicrob Chemother). Continuous infusion (CI) meropenem plasma concentration (solid dark lines); IB meropenem plasma concentration (dotted grey lines); IB meropenem interstitial fluid concentration (ISF) (solid grey lines); CI meropenem ISF concentration (dotted dark lines).
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Figure 3: Observed steady-state plasma and tissue concentrations for meropenem administered to critically ill patients with sepsis by intermittent bolus dosing and continuous infusion (adapted from Roberts et al. 2009, J Antimicrob Chemother). Continuous infusion (CI) meropenem plasma concentration (solid dark lines); IB meropenem plasma concentration (dotted grey lines); IB meropenem interstitial fluid concentration (ISF) (solid grey lines); CI meropenem ISF concentration (dotted dark lines).

Mentions: The debate persists about whether traditional intermittent bolus dosing (IB) or continuous infusion (CI) is clinically preferable for administration of beta-lactam antibiotics. This is despite the fact that beta-lactam PD data suggest advantages for CI compared with IB [18-24], showing time-dependent activity and demonstrating that the duration of time (T) the free drug concentration remains above the minimum inhibitory concentration (MIC; fT>MIC) best describes its bacterial kill characteristics [15] (Figure‚ÄČ1). Thus, administration via CI should be advantageous, because it inevitably produces higher and sustained antibiotic concentrations above the MIC. It also is noteworthy that IB yields unnecessary high peak and low trough concentrations below MIC for much of the dosing interval [25-28] (Figure 2 and Figure 3). The constant and sustainable antibiotic concentrations provided by CI are particularly important for pathogens with high MIC values. Such pathogens are relatively common in the ICU [29-31].


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)

Observed steady-state plasma and tissue concentrations for meropenem administered to critically ill patients with sepsis by intermittent bolus dosing and continuous infusion (adapted from Roberts et al. 2009, J Antimicrob Chemother). Continuous infusion (CI) meropenem plasma concentration (solid dark lines); IB meropenem plasma concentration (dotted grey lines); IB meropenem interstitial fluid concentration (ISF) (solid grey lines); CI meropenem ISF concentration (dotted dark lines).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Observed steady-state plasma and tissue concentrations for meropenem administered to critically ill patients with sepsis by intermittent bolus dosing and continuous infusion (adapted from Roberts et al. 2009, J Antimicrob Chemother). Continuous infusion (CI) meropenem plasma concentration (solid dark lines); IB meropenem plasma concentration (dotted grey lines); IB meropenem interstitial fluid concentration (ISF) (solid grey lines); CI meropenem ISF concentration (dotted dark lines).
Mentions: The debate persists about whether traditional intermittent bolus dosing (IB) or continuous infusion (CI) is clinically preferable for administration of beta-lactam antibiotics. This is despite the fact that beta-lactam PD data suggest advantages for CI compared with IB [18-24], showing time-dependent activity and demonstrating that the duration of time (T) the free drug concentration remains above the minimum inhibitory concentration (MIC; fT>MIC) best describes its bacterial kill characteristics [15] (Figure‚ÄČ1). Thus, administration via CI should be advantageous, because it inevitably produces higher and sustained antibiotic concentrations above the MIC. It also is noteworthy that IB yields unnecessary high peak and low trough concentrations below MIC for much of the dosing interval [25-28] (Figure 2 and Figure 3). The constant and sustainable antibiotic concentrations provided by CI are particularly important for pathogens with high MIC values. Such pathogens are relatively common in the ICU [29-31].

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