title: Bactericidal kinetics of an in vitro infection model of once-daily ceftriaxone plus amikacin against gram-positive and gram-negative bacteria.
abstract: The in vitro efficacy of ceftriaxone plus amikacin combination against gram-positive and gram-negative bacteria, clinically isolated from patients affected by pneumonia in intensive care units, was compared to that of the 2 drugs used alone. The study was performed using a dynamic model in which the human kinetics of the drugs after intramuscular administration was simulated. The antibacterial activity was tested by determining the bacterial cell count (CFU/ml). Killing curves came out from plotting the log CFU/ml versus time. In the same way, ceftriaxone and amikacin concentrations were assayed by HPLC and fluorescence polarization immunoassay, respectively. The results show that ceftriaxone plus amikacin combination exert a high killing activity against all tested strains. The two antibiotics alone initially have a good killing activity but this is followed by bacterial regrowth for all tested isolates. This data supports the results of several clinical studies which have shown a good therapeutic efficacy of ceftriaxone plus amikacin combination in the treatment of severe infections caused by organisms intermediately sensitive to these drugs.
authors.affiliation: Department of Pharmacology, University of Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scaglione
authors.forename: S
authors.initials: S
authors.lastname: Dugnani
authors.forename: G
authors.initials: G
authors.lastname: Demartini
authors.forename: M M
authors.initials: MM
authors.lastname: Arcidiacono
authors.forename: C E
authors.initials: CE
authors.lastname: Cocuzza
authors.forename: F
authors.initials: F
authors.lastname: Fraschini
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D002443:Ceftriaxone / Q000008:administration & dosage / Q000494:pharmacology; D002511:Cephalosporins / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D018410:Pneumonia, Bacterial / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013210:Staphylococcus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D002443:Ceftriaxone; D000583:Amikacin