Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice.
The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomonas aeruginosa was studied in vivo. Granulocytopenic mice infected with P. aeruginosa in the thigh muscle were treated with 1-hr or 3-hr injections of gentamicin, ticarcillin, or gentamicin-ticarcillin. Plasma pharmacokinetics of the drugs were correlated with antibacterial activity. Gentamicin injected every 1 hr tended to be less active than gentamicin injected at longer intervals. In contrast, ticarcillin given every 1 hr was significantly more efficacious than equivalent total doses injected every 3 hr. The dosing schedule of gentamicin-ticarcillin was again important for ticarcillin but did not appreciably affect the antibacterial activity of gentamicin. Thus, antimicrobial chemotherapy of P. aeruginosa infections in the granulocytopenic host might be improved by administering ticarcillin rather than gentamicin as a constant infusion.
D000380:Agranulocytosis / Q000150:complications*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005839:Gentamicins / Q000378:metabolism / Q000627:therapeutic use*; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D010406:Penicillins / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D013982:Ticarcillin / Q000378:metabolism / Q000627:therapeutic use*
D005839:Gentamicins; D010406:Penicillins; D013982:Ticarcillin