Animal model distinguishing in vitro from in vivo carbenicillin-aminoglycoside interactions.

Antimicrobial Agents and Chemotherapy
J A PieperJ J Schentag

Abstract

Aminoglycosides and carbenicillin are frequently co-administered to patients with serious gram-negative infections. Aminoglycosides are inactivated by carbenicillin in vitro, and a loss of antibacterial activity of both antibiotics results. Although these interactions are presumed to occur in vivo, previous studies have not used assay methodology that can distinguish inactivation occurring prior to and during microbiological assay from inactivation in vivo. To address this problem, we gave seven bilaterally nephrectomized mongrel dogs doses designed to achieve simultaneous therapeutic serum concentrations of aminoglycosides and carbenicillin. Serum samples were tested by radioimmunoassay on three occasions: immediately, to determine in vivo interactions, and at 24 h and 1 week to assess the time course of in vitro inactivation. In comparison with immediate radioimmunoassay, gentamicin and tobramycin concentrations decreased by 39 and 53%, respectively, when assayed at 24 h (P < 0.05) and by 75 and 82% when assayed at 7 days (P < 0.001). In contrast, amikacin concentrations were reduced by only 9 and 30% at 24 h and 7 days. Tobramycin concentrations were also determined by immediate microbiological assay and were found to be sim...Continue Reading

References

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Citations

Oct 1, 1993·British Journal of Clinical Pharmacology·G W RobertsA J Martin
Feb 1, 1982·Antimicrobial Agents and Chemotherapy·M I ThompsonJ M Matsen
Oct 1, 1983·Antimicrobial Agents and Chemotherapy·A LauR Sharifi
Nov 1, 1984·Antimicrobial Agents and Chemotherapy·A J Falkowski, R J Creger
Aug 1, 1985·Antimicrobial Agents and Chemotherapy·S M Wallace, L Y Chan
Feb 1, 1986·Antimicrobial Agents and Chemotherapy·D N WrightJ M Matsen
May 1, 1983·Antimicrobial Agents and Chemotherapy·H KonishiH Yamashina
May 1, 1989·Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons·P Van der Bijl, H I Seifart
Mar 12, 2005·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M Bernabeu-WittelJ Pachón
Feb 1, 1983·Drug Intelligence & Clinical Pharmacy·D R Guay
Jul 1, 1982·Annals of Clinical Biochemistry·L White

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