title: In vitro bactericidal activity and post-antibiotic effect of dactimicin, a new aminoglycoside, alone and in combination with other antibiotics.
abstract: The bactericidal activity of dactimicin, a novel aminoglycoside, has been tested in vitro in combination with piperacillin, mezlocillin and ceftazidime against freshly isolated Gram-negative and Gram-positive aerobes and compared with that of amikacin. Using the checkerboard test, the combination of dactimicin and amikacin with the other drugs resulted in a synergistic interaction with the Enterobacteriaceae strains analysed in 36 out of 39 and 37 out of 39 cases, respectively. Antagonism was never encountered. With the Pseudomonas isolates, indifference prevailed with dactimicin, whereas synergism was observed with amikacin in combination with the other drugs. No case of antagonism was encountered. When the time-kill system was employed, synergism prevailed, indifference was a rare case, and antagonism was not observed. In experiments carried out with dactimicin-susceptible staphylococcal and enterococcal isolates, a synergistic outcome was obtained employing both methods. Dactimicin induced a post-antibiotic effect (PAE) which ranged from about 1 h with Enterobacter cloacae to 3 h with Escherichia coli after exposure of the bacteria for 1 h to 4 x MIC. The PAE was also evaluated employing several drug associations. An average of 0.6 h PAE was apparent when dactimicin was combined with piperacillin, mezlocillin and ceftazidime, and the bacteria were exposed for 1 h to drug concentrations corresponding to one-half their MICs.
authors.affiliation: Institute of Microbiology, University of Genoa, Italy.
authors.forename: E A
authors.initials: EA
authors.lastname: Debbia
authors.forename: G C
authors.initials: GC
authors.lastname: Schito
authors.forename: S
authors.initials: S
authors.lastname: Stefani
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C023527:dactimicin