QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moriyama, B. Articles by Walsh, T. J Search for Related Content PubMed PubMed Citation Articles by Moriyama, B. Articles by Walsh, T. J

INFECTIOUS DISEASES

Continuous-Infusion β-Lactam Antibiotics During Continuous Venovenous Hemofiltration for the Treatment of Resistant Gram-Negative Bacteria

Clinical Pharmacist, Pharmacy Department, National Institutes of Health (NIH) Clinical Center, Bethesda, MD

Stacey A Henning, PharmD

Clinical Pharmacist, Pharmacy Department, NIH Clinical Center

Melinda M Neuhauser, PharmD MPH

Clinical Pharmacist, US Department of Veteran Affairs, Pharmacy Benefits Management Services, Hines, IL

Robert L Danner, MD

Senior Investigator, Critical Care Medicine Department, NIH Clinical Center

Thomas J Walsh, MD

Senior Investigator, Chief, Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda

Reprints: Dr. Walsh, CRC 1-5750, 10 Center Dr., Bethesda, MD 20892, fax 301/480-2308, walsht{at}mail.nih.gov

OBJECTIVE: To describe the rationale, principles, and dosage calculations for continuous-infusion β-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH).

DATA SOURCES: A MEDLINE search (1968-November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter; hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different β-lactam antibiotics.

STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and human studies were evaluated that used continuous-infusion β-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of β-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy.

DATA SYNTHESIS: Continuous infusion of β-lactam antibiotics, maintaining drug concentrations 4-5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several β-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltration. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous β-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center.

CONCLUSIONS: Continuous infusion of β-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of β-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.

Key Words: Acinetobacter baumannii, β-lactam, continuous infusion, continuous venovenous hemofiltration, Pseudomonas aeruginosa

Published Online, July 7, 2009. www.theannals.com, DOI 10.1345/aph.1L638

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-09-012-H01-P