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Updated: Aug 16, 2026
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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Continuous infusion of beta-lactam antibiotics
1Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust, England.
Clinical Pharmacokinetics
|December 5, 1998
Summary
Continuous infusion therapy for penicillins and cephalosporins shows promise for Gram-negative infections, especially when conventional treatments fail. Further research is needed for monobactams and carbapenems.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Laboratory data support continuous infusion (CI) for penicillins and cephalosporins.
- Clinical data for CI are primarily available for cephalosporins.
- Penicillins exhibit time-dependent killing and post-antibiotic effect (PAE) against Gram-positives, while cephalosporins also rely on time above minimum inhibitory concentration (T > MIC).
Purpose of the Study:
- To review the evidence for continuous infusion antibiotic therapy.
- To compare the pharmacodynamics and clinical efficacy of different beta-lactam antibiotics when administered via CI.
- To provide guidance on the clinical application of CI for specific infections.
Main Methods:
- Review of laboratory, animal, and human pharmacokinetic and pharmacodynamic data.
- Analysis of existing clinical data for cephalosporins, penicillins, monobactams, and carbapenems.
- Evaluation of factors influencing CI efficacy, such as T > MIC and drug concentration at steady-state (Css).
Main Results:
- For penicillins and cephalosporins, T > MIC is the key determinant of outcome.
- Ceftazidime CI can achieve Css > 20 mg/L, demonstrating efficacy in neutropenic patients with Gram-negative infections.
- Cefuroxime CI resulted in lower doses and shorter treatment durations.
- Carbapenems exhibit concentration-dependent killing and PAE, with a less stringent T > MIC requirement compared to other beta-lactams.
Conclusions:
- CI with penicillins and cephalosporins should be considered for Gram-negative infections unresponsive to conventional therapy.
- A loading dose is recommended for rapid Css achievement during CI.
- Individualized Css targets based on pathogen MIC are crucial for optimizing CI therapy, particularly for penicillins and cephalosporins.
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