Use of Prolonged-Infusion Beta-Lactam Antibiotics

Publication Date: August 24, 2023
Last Updated: September 1, 2023

Summary of Recommendations

Preclinical targets for reductions in CFU are 40%–70% fT>MIC for SI and up to 4-h EI, and 100% fT>MIC with concentrations that exceed up to four to eight times free drug over the steady-state concentration (fCss) for CI. No absolute target guarantees suppression of resistance but exceeding the MIC by four to six times may minimize resistance. (U, U)
620
In vitro and animal data, predominately with gram-negative bacteria, demonstrated equivalent or better killing for PI compared with SI; this is likely attributable to greater fT>MIC with PI compared with SI. (U, U)
620
β-lactams given by PI may reduce the emergence of resistance. β-lactam agent, the bacterial species, MIC, and initial inoculum are important factors affecting the emergence of resistance. (U, U)
620
We suggest that β-lactam TDM and personalized dosing may be considered on a patient-by-patient, indication-by-indication, and drug-by-drug basis until further evidence is available. We cannot recommend for or against routine TDM for PI β-lactams at this time. (U, U)
620
There is insufficient evidence to recommend a single concentration or exposure to target when performing β-lactam TDM; however, evidence does exist for a minimum exposure. When TDM is performed, we suggest minimum plasma exposures of at least 50%–70% fT>MIC be targeted for β-lactams when administered as SI and EI. For β-lactams administered as CI, we suggest 100% fT>MIC with concentrations at least four times the MIC. (U, U)
620
There are general stability concerns that should be considered on a drug-by-drug basis when delivering β-lactams by PI. (U, U)
620
We suggest PI β-lactam antibiotics over SI to reduce mortality or increase clinical cure among severely ill adult patients, particularly those with gram-negative infections. (C, VL)
620
We cannot recommend for or against PI β-lactam antibiotics over SI to reduce mortality and increase clinical cure among nonseverely ill adult patients. (C, VL)
620
We cannot recommend for or against the use of PI over SI to provide a safety advantage and reduce adverse effects of β-lactam antibiotics. (C, VL)
620
We suggest use of a loading dose over no loading dose when initiating CI β-lactam antibiotics to improve clinical success and we cannot recommend for or against a loading dose with EI. (C, VL)
620
We cannot recommend for or against routine use of PI for any specific clinical situations or in any specific patient populations (e.g., severely ill, obese, neonates) to improve efficacy of β-lactam agents in the pediatric population. (C, VL)
620
We cannot recommend for or against routine use of PI to improve efficacy of β-lactam agents in obese patients. (U, U)
620

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Use of Prolonged-Infusion Beta-Lactam Antibiotics

Authoring Organizations

Publication Month/Year

August 24, 2023

Last Updated Month/Year

September 12, 2023

Document Type

Consensus

Country of Publication

Global

Document Objectives

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, health systems pharmacist, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D007262 - Infusions, Intravenous, D018440 - beta-Lactam Resistance, D047090 - beta-Lactams

Keywords

topical antibiotics, beta-lactams, β-lactam, prolonged infusion

Source Citation

Hong LT, Downes KJ, FakhriRavari A, Abdul-Mutakabbir JC, Kuti JL, Jorgensen S, Young DC, Alshaer MH, Bassetti M, Bonomo RA, Gilchrist M, Jang SM, Lodise T, Roberts JA, Tängdén T, Zuppa A, Scheetz MH. International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary. Pharmacotherapy. 2023 Aug;43(8):736-739. doi: 10.1002/phar.2844. PMID: 37615244.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
189
Literature Search Start Date
October 18, 2020
Literature Search End Date
October 1, 2021