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INFECTIOUS DISEASES

Differences Between Ceftriaxone and Cefotaxime: Microbiological Inconsistencies

Professor, Pharmacy and Medicine, Director of Clinical Research in Family Medicine, Departments of Pharmacy Practice and Family Medicine, University of Florida, Gainesville, FL

D Wesston Boatwright, PharmD

Senior Medical Liaison, Medical Affairs, Roche Laboratories, Inc., Jacksonville, FL

Mark Camblin, PhD

Technical Director, Microbiology/Immuno-Serology, St. Mary's Health System, Knoxville, TN

Diane C Halstead, PhD D(ABMM) F(AAM)

Director, Infectious Disease Laboratories, Jacksonville Pathology Associates, P.A./Baptist Health, Jacksonville, FL

Mark E Jones, PhD

Scientific Director, Eurofins Medinet Inc., Herndon, VA

Roger Sanderson, MA BSN

Epidemiologist, Florida Department of Health, Tampa, FL

Reprints: Dr. Gums, Departments of Pharmacy Practice and Family Medicine, University of Florida, 625 SW Fourth Ave., Gainesville, FL 32601, fax 352/392-7766, jgums{at}ufl.edu

OBJECTIVE: To review data to determine why pneumococcal isolates appear to be increasingly resistant to cefotaxime, historically regarded as having the same in vitro susceptibility to ceftriaxone, and what this observation might imply clinically.

DATA SOURCES: Literature was accessed through MEDLINE (1966-October 2007) using the MeSH terms cefotaxime, ceftriaxone, susceptibility, microbial sensitivity tests, antibiotics, pneumococcal infections, Streptococcus pneumoniae, resistance, and cephalosporin resistance. Abstracts and surveillance databases were reviewed and unpublished data were provided by state departments of health and institutions.

STUDY SELECTION AND DATA EXTRACTION: All articles published in the English language that were identified from the data sources were evaluated.

DATA SYNTHESIS: An experimental model of pneumococcal infection in mice conducted 2 decades ago predicted that the delta T minimum inhibitory concentration (MIC) varied less for ceftriaxone than for cefotaxime. Studies of plasma and serum concentrations show that ceftriaxone remains at a concentration above the S. pneumoniae MIC for 100% of the dosing interval at 12 hours. Types of MIC susceptibility test methods for ceftriaxone and cefotaxime used against S. pneumoniae respiratory isolates were found to be similar. Data from state and county health departments found microbiological discrepancies between ceftriaxone and cefotaxime. In areas with high rates of penicillin-resistant S. pneumoniae (PRSP), isolates were twice as susceptible to ceftriaxone versus cefotaxime. Surveillance databases consistently show differences between susceptibility of S. pneumoniae to cefotaxime versus ceftriaxone over time. MIC and pulsed-field gel electrophoresis studies suggest that phenotypic discrepancies may account for penicillin resistance. Ongoing studies are examining S. pneumoniae isolates at the molecular level to determine the basis of difference in resistance to cefotaxime and ceftriaxone.

CONCLUSIONS: An increase in rates of PRSP and differences in S. pneumoniae isolate susceptibility between ceftriaxone and cefotaxime emphasize the necessity for hospital laboratories to detect these changes as they occur. Clinicians should select the most appropriate agent for patients with S. pneumoniae.

Key Words: cefotaxime, ceftriaxone, Streptococcus pneumoniae

Published Online, December 19, 2007. www.theannals.com, DOI 10.1345/aph.1H620

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-08-001-H01