Effect of concentration and time upon inactivation of tobramycin, gentamicin, netilmicin and amikacin by azlocillin, carbenicillin, mecillinam, mezlocillin and piperacillin

J Pharmacol Exp Ther. 1981 May;217(2):345-9.


Carbenicillin and ticarcillin have been shown to inactivate aminoglycoside antibiotics. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycoside antibiotics at two concentrations with azlocillin, mecillinam, mezlocillin, piperacillin and carbenicillin at three concentrations. By linear regression analysis, the inactivation of each aminoglycoside antibiotic was shown to be directly proportional to the concentration of the semisynthetic penicillin. Aminoglycoside inactivation was greater after 72 hr of incubation with the penicillins than after 24 hr of incubation. Inactivation by each semisynthetic penicillin was greater for tobramycin and gentamicin than for netilmicin and amikacin, especially at higher concentrations of the penicillins. At concentrations of 500 microgram/ml, significantly less inactivation of amikacin occurred when compared to netilmicin. There was little difference in inactivation of a specific aminoglycoside by any of the semisynthetic penicillin antibiotics. No significant change in aminoglycoside activity occurred when the aminoglycosides were stored with the semisynthetic penicillin derivatives at -70 degrees C for 30 days. Conclusions from this study are: 1) serum specimens containing aminoglycoside-penicillin combinations should be tested immediately or frozen before antibiotic assay and 2) aminoglycoside inactivation by the newer semisynthetic penicillins may be important in patients with renal failure who are receiving these antimicrobial agents.

MeSH terms

  • Amdinocillin / pharmacology
  • Amikacin / antagonists & inhibitors
  • Aminoglycosides / antagonists & inhibitors
  • Anti-Bacterial Agents / antagonists & inhibitors*
  • Azlocillin
  • Carbenicillin / pharmacology
  • Gentamicins / antagonists & inhibitors
  • Mezlocillin
  • Netilmicin / antagonists & inhibitors
  • Penicillins / pharmacology*
  • Piperacillin
  • Time Factors
  • Tobramycin / antagonists & inhibitors


  • Aminoglycosides
  • Anti-Bacterial Agents
  • Gentamicins
  • Penicillins
  • Netilmicin
  • Amikacin
  • Carbenicillin
  • Azlocillin
  • Mezlocillin
  • Amdinocillin
  • Tobramycin
  • Piperacillin