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Continuous Infusion of Beta-lactam Antibiotics

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Book cover Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

Abstract

For beta-lactam antibiotics continuous infusion can be used to optimise antibiotic therapy. Pre-clinical studies in rodents and in vitro studies have shown the benefits of continuous infusion when compared to intermittent dosing. Pharmacokinetic studies in humans have shown an improved probability of target attainment for continuous infusion. However, the relationship between continuous infusion and improved clinical outcome is ambiguous. The superiority of continuous infusion over intermittent dosing in clinical outcome studies is most often documented in special subgroups, such as critically ill patients or patients infected with less-susceptible micro-organisms. Methods to calculate doses during continuous infusion and practical issues, such as stability of antimicrobial solutions, are described.

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Abbreviations

CF:

Cystic fibrosis

CL:

Clearance

C max :

Maximum concentration

FDA:

Food and Drug Administration

FEV1:

Volume exhaled during the first second of a forced expiratory manoeuver started from the level of total lung capacity

FVC:

Forced vital capacity; total amount of air that can forcibly be blown out after full inspiration

ICU:

Intensive care unit

Iv:

Intravenous

IVPM:

In vitro pharmacokinetic–pharmacodynamic (PK/PD) models

MCS:

Monte Carlo simulation

MIC:

Minimum inhibitory concentration

MSW:

Mutation selection window

PD:

Pharmacodynamics

PD50:

Daily dose required to protect 50 % of the animals from mortality

PK:

Pharmacokinetics

PTA:

Probability of target attainment

TBC:

Total body clearance

Vd:

Volume of distribution

%f  T > MIC:

Percentage of time that the unbound concentrations is above the MIC

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Authors and Affiliations

  1. Department of Medical Microbiology, St. Elisabeth Hospital Hilvarenbeekseweg 60, 5022GC, Tilburg, The Netherlands

    Anouk E. Muller M.D., Ph.D.

  2. Department of Medical Microbiology, Radboudumc, Radboud University Nijmegen, Geert Grooteplein-zuid 10, Route 777, 6525 GA, Nijmegen, The Netherlands

    Johan W. Mouton M.D., Ph.D., F.I.D.S.A.

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  1. Anouk E. Muller M.D., Ph.D.
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  2. Johan W. Mouton M.D., Ph.D., F.I.D.S.A.
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Correspondence to Anouk E. Muller M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA

    Alexander A. Vinks

  2. Dept. Pharmaceutics, University of Florida, Gainesville College of Pharmacy, Gainesville, Florida, USA

    Hartmut Derendorf

  3. Dept. of Medical Microbiology, Radboudumc, Radboud University Nijmegen, Nijmegen, The Netherlands

    Johan W. Mouton

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Muller, A.E., Mouton, J.W. (2014). Continuous Infusion of Beta-lactam Antibiotics. In: Vinks, A., Derendorf, H., Mouton, J. (eds) Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75613-4_10

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