In vitro inactivation of aminoglycosides by cephalosporin antibiotics

D N Wright1, D A Marble, B Saxon

  • 1Department of Pathology, School of Medicine, University of Utah, Salt Lake City.

Insights

Aminoglycoside antibiotics show varying in vitro stability when combined with cephalosporins. Amikacin and tobramycin are most stable, while netilmicin is least stable, requiring laboratory precautions with certain cephalosporins.

Area of Science:

  • Pharmacology
  • Microbiology
  • Clinical Chemistry

Background:

  • In vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins poses challenges for accurate antibiotic assays.
  • The increasing development of new cephalosporins and their combined use with aminoglycosides necessitates understanding their stability.

Purpose of the Study:

  • To determine the in vitro stability of 28 different aminoglycoside-cephalosporin combinations.
  • To identify which aminoglycosides and cephalosporins exhibit greater stability in combination.

Main Methods:

  • Tested 28 combinations of four aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) with seven cephalosporins (cefazolin, cefoxitin, cefoperazone, cefotaxime, ceftazidime, cefsulodin, cefpiramide).
  • Incubated mixtures at 37°C and sampled at 0, 8, and 24 hours to assess stability.
  • Evaluated stability at varying concentrations of cephalosporins (100, 200, 300 µg/mL).

Main Results:

  • Amikacin and tobramycin demonstrated the highest stability among the tested aminoglycosides.
  • Netilmicin exhibited the least stability.
  • Cefoxitin, ceftazidime, and cefotaxime were found to be the least inactivating cephalosporins.

Conclusions:

  • Aminoglycosides are relatively stable when combined with first- and second-generation cephalosporins.
  • Laboratory precautions are advised when measuring aminoglycoside levels in the presence of third-generation cephalosporins due to potential inactivation.

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